We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The ACTA2 gene makes a protein called smooth muscle alpha (ɑ)-2 actin (ɑ-2 actin). The ɑ-2 actin protein is found primarily in our smooth muscles (muscles that line our blood vessels, stomach, intestines, and other internal organs). Smooth muscles relax and contract automatically as part of their normal function, and the ɑ-2 actin protein works with other proteins to help the smooth muscles contract, which helps them to keep their shape instead of stretching out too much while blood is pumping through.

If someone has a harmful change (called a pathogenic variant) in one of their ACTA2 genes, then their body does not make as much ɑ-2 actin protein as it should. If there is not enough ɑ-2 actin protein, then the smooth muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to health issues like familial thoracic aortic aneurysm and dissection. Some specific pathogenic variants in the ACTA2 gene can also cause other health issues like patent ductus arteriosus and coarctation of the aorta.

Pathogenic variants in the ACTA2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the ACTA2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for ACTA2

Genetic testing for pathogenic variants in ACTA2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the ACTA2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The ACTC1 gene makes a protein called the cardiac muscle alpha actin (CMAA) protein. The CMAA protein is found primarily in the heart muscles in our body. The CMAA protein works with other proteins to create the force that is needed for our heart muscles to contract. This muscle contraction is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their ACTC1 genes, then their body does not make as much CMAA protein as it should. If there is not enough CMAA protein, then the heart muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, left ventricular noncompaction, and familial dilated cardiomyopathy.

Pathogenic variants in the ACTC1 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the ACTC1 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for ACTC1

Genetic testing for pathogenic variants in ACTC1 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the ACTC1 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

Familial adenomatous polyposis (also called FAP) is caused by pathogenic (or harmful) variants in the APC gene. FAP is typically characterized by a person developing more than 100 but usually less than 1000 colon polyps within their lifetime, putting them at a very high risk of early onset colon cancer (under age 50). In addition to colon polyps, individuals with FAP are more susceptible to develop some rarer medical conditions:

• Polyps in the stomach or the small bowel
• Desmoids (tumors of fibrous connective tissue)
• Osteomas (benign tumors of the bone, often on the skull)
• Having more teeth than usual (supernumerary teeth)
• Benign freckling on the retina of the eye, called CHRPE

Colon cancer is the main concern for individuals with FAP, however research has shown that there is a small but increased chance to develop other cancers:

Sometimes individuals with a pathogenic variant in the APC gene develop many polyps (10-100 polyps) but not over 100 polyps that individuals with FAP typically will have. These individuals are considered to have Attenuated Familial Adenomatous Polyposis (or AFAP). Those with AFAP are still at high risk of colon cancer, but this risk is lower and often later onset (after age 50) than in those with classic FAP. Similar to classic FAP, those with AFAP are also at increased risk of polyps in the stomach or small intestine, thyroid cancer, and duodenal/intestinal cancer; however the rarer features of FAP (CHRPE, desmoid tumors) are much less common in AFAP.

Causes of FAP/APAP

FAP and AFAP are both are inherited in an autosomal dominant pattern, meaning that children of someone who carries a pathogenic variant each have a 50% risk to inherit the variant and associated cancer risks. Women and men have the same chances to inherit and pass down variants in these genes, therefore both sides of the family are important to look at when trying to determine if someone has a higher chance to have FAP or AFAP.  

FAP and AFAP can both run in families; however, about 30% of the time an individual with FAP is the first one in the family to have the condition due to random chance (called “de novo”). Those with a new diagnosis of FAP or AFAP in a family can still pass it on to future generations.

Genetic Testing for FAP/AFAP

Genetic testing for pathogenic variants that cause FAP/AFAP has been available for many years, and the testing methods have changed and improved over time. There are several different ways to approach to testing in these genes, depending on the history and any prior testing that may have been done. Different approaches include:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the APC gene.
• Gene panels: Newer, more broadly based gene tests that would include not only the APC gene, but other genes known or suspected to be associated with colon polyps and increased cancer risks

Who should be offered testing for FAP?
The National Comprehensive Cancer Network (NCCN) is a group of medical professionals that regularly meet to look over any updates in research studies and determine recommendations for who should be considered at a higher risk for one of these gene mutations, and thus should be offered genetic testing.

• Individuals with a personal history of at least 20 colon polyps (specifically adenomatous ones) in their lifetime
• Individuals with a family history of a known APC pathogenic variant in a relative
• Testing can be considered if a person has only developed 10-20 colon polyps in their lifetime especially if these were early onset (under age 50) or there is a strong family history of colon polyps
• Testing can be carefully considered in those with a desmoid tumor, hepatoblastoma, a specific type of thyroid cancer called cribiform-morular papillary thyroid cancer, or with CHRPE that is multifocal or present in both eyes

Those who undergo testing for the APC gene due to a personal history of many colon polyps should also be offered testing for another genetic predisposition to colon polyps called MUTYH-associated polyposis (MAP). These two conditions are caused by separate genetic variants but it is often difficult to distinguish between them without genetic testing.

Associated Condition of APC: Colonic Polyposis of Unknown Etiology (CPUE)
It is fairly common for individuals to have negative or inconclusive genetic testing for FAP despite having developed many colon polyps. It is likely that researchers have not yet discovered all of the genes or other factors that can cause someone to develop colon polyps. If someone has developed at least 20 colon polyps (adenomatous type) in their lifetime but their genetic testing does not show that they have a genetic variant, they are designated to have colonic polyposis of unknown etiology (CPUE).

Even though they do not have FAP or another genetic cause of their polyps, individuals with CPUE should still have close surveillance for future colon polyps. This includes a colonoscopy every 1-2 years to remove any new polyps as they appear.

Close family members of those who have CPUE do not need genetic testing but should also undergo close surveillance starting at least at age 40 (or younger if there is early onset colon polyps or colon cancer in the family). This includes colonoscopies at least every 3-5 years, but maybe more frequent if the individual with CPUE has had more than 100 polyps removed or if the family member has polyps found on their own colonoscopy. A discussion with a genetic counselor and/or a high-risk gastrointestinal screening specialist can help determine what is recommended specifically for you and your family members.

Treatment/Management for FAP/AFAP

If you are tested and found to have FAP or AFAP, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on the updated guidelines of the (NCCN), but may be tailored to your specific medical and family history.  

All individuals with FAP and AFAP should have a colonoscopy at least every year to remove new colon polyps which may grow into colorectal cancer. This screening should start around age 10-15 because polyps can start to grow even at a young age. The good news is that this screening for colon cancer is highly effective in reducing the chance that someone would develop colon cancer and reduces the severity of colon cancer.

On the other hand, if polyps become too numerous to remove successfully, a physician will likely recommend removing the colon (colectomy). Patients should be carefully counseled about the risks, disadvantages, and benefits of the various options for colectomy. Individuals with FAP who have had a colectomy will still require regular follow up with their gastrointestinal providers to check for polyps that could develop in the ileum (last section of the small intestine) and/or the rectum.

An upper endoscopy (EGD) to look at the stomach, duodenum (the first part of the small intestine immediately beyond the stomach), and ampulla of Vater (a dilated part of the duodenum) should be completed every 4 years starting at age 20-25 years. This should be repeated more frequently if adenomatous polyps are present.

Individuals with FAP should have an annual thyroid examination starting in the late teens. They should also have an annual physical with their physician that includes a neurological exam and a physical exam of the abdomen to check for desmoid tumors. CT or MRI imaging of the abdomen could be considered if there is a family history of desmoid tumors.

In families with FAP and a history of pancreatic cancer, individualized screening may be offered based on the history, but no specific guidelines currently exist.  

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The APOB gene makes a protein called apolipoprotein B. Apolipoprotein B proteins perform many jobs in the body, including helping to carry fat and cholesterol from our intestines into our bloodstream. It also helps to attach cholesterol to LDL receptors (made by the LDLR gene) on our cells, which bring cholesterol into the cells where it can be used, stored, or gotten rid of. This process or removing excess cholesterol happens primarily in the liver.

The amount of the apolipoprotein B protein that is in the body determines how well the cholesterol can attach to the the LDL receptors. If someone has a harmful error (called a pathogenic variant) in one of their APOB genes, then their body is not going to make enough of the apolipoprotein B protein as it should. If there is not enough apolipoprotein B, then the cholesterol cannot be captured and processed as easily by the cells. This can lead to the cholesterol building up in the body, which can cause the signs and symptoms we associated with familial hypercholesterolemia.

Recent studies have shown that people who have FH that is caused by a pathogenic variant in the APOB gene tend to be less severe than those who carry pathogenic variants in the LDLR or PCSK9 genes.

Pathogenic variants in the APOB gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the APOB gene and have the same chances to inherit and pass down pathogenic variants. Almost all people who have a pathogenic variant in the APOB gene have a parent who also carries it.

Genetic Testing for APOB

Genetic testing for pathogenic variants in APOB is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the APOB gene, but other genes known or suspected to be associated with familial hypercholesterolemia

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

Pathogenic (or harmful) variants in the ATM gene have been associated with an increased lifetime risk of breast cancer (up to 38-69% lifetime risk). Some studies have also suggested associated risk for other cancers, such as pancreatic or prostate cancer, although these are not as well established.

ATM gene variants related to cancer risk are inherited in an autosomal dominant pattern, meaning that children of someone who carries a variant each have a 50% risk to inherit the variant and associated cancer risks. Notably, women and men both have the ATM gene and have the same chances to inherit and pass down variants in these genes. Therefore, both sides of the family are important when assessing inherited risk.

Genetic Testing for ATM

Genetic testing for pathogenic variants in ATM are currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known mutation in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable mutations in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the ATM gene, but other genes known or suspected to be associated with increased cancer risks

Treatment/Management for ATM

If you are tested and found to have a mutation in the ATM gene, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic.  General recommendations are included here based on updated guidelines of the NCCN, but may be tailored to your specific medical and family history.

For women, breast cancer screening recommendations include starting annual mammograms at age 40 with consideration of breast MRI starting at age 40, or 5-10 years prior to the earliest diagnosis of breast cancer in the family, whichever is earlier.

If there is a history of other cancers in the family, your doctor or healthcare provider may recommend additional, earlier, or more frequent screening for those other cancers based on the family history.

Associate Condition of ATM: Ataxia Telangiectasia

The above information about cancer risks is relevant for people who have a single mutation in the ATM gene. Importantly, if a child inherits mutations in both copies the ATM gene (one mutation from mom and one mutation from dad), this causes a different genetic condition called ataxia telangiectasia. Ataxia telangiectasia is a rare autosomal recessive condition that causes progressive problems with movement and coordination (ataxia), enlarged blood vessels in the eyes and skin (telangiectasias), and increased risk for infection and cancer in children (e.g. leukemia, lymphoma). Therefore, people with a mutation in the ATM gene who are pregnant or planning to have children are recommended to seek genetic counseling to clarify the risk to their children.

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body, and those genes are located in our DNA. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The BRCA1 gene makes a protein called the BRCA1 protein. As we go through life, our DNA can get damaged in many different ways, including exposures in the environment, or when our cells are dividing to make new cells. Sometimes this damage happens due to causes that we do not yet know about. As this damage builds up, it can cause a cell to grow out of control. This can lead to a tumor, which can then lead to cancer. The BRCA1 protein works with other proteins to fix this damage that happens in the DNA, thus preventing the cells from growing out of control. Repairing this damaged DNA helps to prevent tumors from forming.

If someone has a harmful change (called a pathogenic variant) in one of their BRCA1 genes, then their body does not make as much BRCA1 protein as it should. Without enough BRCA1 protein, our body can not repair our damaged DNA as well as it should be able to. This can allow the damage to build up in cells more quickly, which causes the increased risk for BRCA-related cancers. Someone with HBOC is not producing enough BRCA1 protein from birth, which is also why people with HBOC can be diagnosed with these cancers at an earlier age than would normally be expected.

Associated Risks for BRCA1

There are increased risks for certain types of cancer in individuals who have a pathogenic variant in the BRCA1 gene, although the associated cancers and lifetime risks are different between men and women:

Inheritance Patterns of BRCA1

Pathogenic variants in the BRCA1 gene are inherited in an autosomal dominant pattern, meaning that children of someone who has a pathogenic variant in BRCA1 have a 50% chance to inherit the variant and associated cancer risks. Notably, women and men both have the BRCA1 gene and have the same chances to inherit and pass down pathogenic variants. Therefore, both sides of the family are important when assessing inherited risk. Almost all people who have a pathogenic variant in BRCA1 will have a parent who also carries it.

Genetic Testing for BRCA1

Genetic testing for pathogenic variants in BRCA1 has been available for many years, and the testing methods have changed and improved over time. There are several different ways to approach testing depending on the medical and family history, and any prior testing that may have been done. Different approaches include:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the genes. If past testing included full gene sequencing but not the rearrangement analysis, this additional testing can be ordered to evaluate for these types of variants that would have been missed on older testing.
• Founder variant testing: Testing specific to the three common pathogenic variants found in the Ashkenazi Jewish population
• Gene panels: Newer, more broadly based gene tests that would include not only the BRCA1 gene, but other genes known or suspected to be associated with increased cancer risks

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body, and those genes are located in our DNA. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The BRCA2 gene makes a protein called the BRCA2 protein. As we go through life, our DNA can get damaged in many different ways, including exposures in the environment, or when our cells are dividing to make new cells. Sometimes this damage happens due to causes that we do not yet know about. As this damage builds up, it can cause a cell to grow out of control. This can lead to a tumor, which can then lead to cancer. The BRCA2 protein works with other proteins to fix this damage that happens in the DNA, thus preventing the cells from growing out of control. Repairing this damaged DNA helps to prevent tumors from forming.

If someone has a harmful change (called a pathogenic variant) in one of their BRCA2 genes, then their body does not make as much BRCA2 protein as it should. Without enough BRCA2 protein, our body can not repair our damaged DNA as well as it should be able to. This can allow the damage to build up in cells more quickly, which causes the increased risk for BRCA-related cancers. Someone with HBOC is not producing enough BRCA2 protein from birth, which is also why people with HBOC can be diagnosed with these cancers at an earlier age than would normally be expected.

Associated Risks for BRCA2

There are increased risks for certain types of cancer in individuals who have a pathogenic variant in the BRCA2 gene, although the associated cancers and lifetime risks are different between men and women:

Inheritance Patterns for BRCA2

Pathogenic variants in the BRCA2 gene are inherited in an autosomal dominant pattern, meaning that children of someone who has a pathogenic variant in BRCA2 have a 50% chance to inherit the variant and associated cancer risks. Notably, women and men both have the BRCA2 gene and have the same chances to inherit and pass down pathogenic variants. Therefore, both sides of the family are important when assessing inherited risk. Almost all people who have a pathogenic variant in BRCA2 will have a parent who also carries it.

If someone inherits a pathogenic variant in both of their BRCA2 genes (one from each parent), then they have a genetic condition called Fanconi anemia, which primarily affects the bone marrow. People with Fanconi anemia can have physical signs, including patches of skin that are different colors, skeletal problems, issues with their kidneys and urinary tract, heart defects, eye and ear malformations, and hearing loss. There is also an increased risk for a blood cancer called acute myeloid leukemia, or tumors in the head, neck, skin, gastrointestinal system, or genital tract.

Genetic Testing for BRCA2

Genetic testing for pathogenic variants in BRCA2 has been available for many years, and the testing methods have changed and improved over time. There are several different ways to approach to testing depending on the medical and family history, and any prior testing that may have been done. Different approaches include:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the genes. If past testing included full gene sequencing but not the rearrangement analysis, this additional testing can be ordered to evaluate for these types of variants that would have been missed on older testing.
• Founder variant testing: Testing specific to the three common pathogenic variants found in the Ashkenazi Jewish population
• Gene panels: Newer, more broadly based gene tests that would include not only the BRCA2 gene, but other genes known or suspected to be associated with increased cancer risks

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The CASQ2 gene makes a protein called calsequestrin 2. The calsequestrin 2 protein helps to store calcium. The amount of calcium in the cells of our heart controls when our heart muscles contract and relax, which make the heart beat at a normal rhythm, The calcium that is stored by the CASQ2 gene is primarily in the heart muscles.

If someone has a harmful change (called a pathogenic variant) in one of their CASQ2 genes, then their body is not going to make enough of the calsequestrin 2 protein as it should. If there is not enough calsequestrin 2 protein, then there will not be enough stored calcium. This would mean that the heart’s ability to contract and relax (and thus beat) at a normal rate is not going to work as well as it should. This can lead to a heart condition called catecholaminergic polymorphic ventricular tachycardia.

Pathogenic variants in the CASQ2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the CASQ2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for CASQ2

Genetic testing for pathogenic variants in CASQ2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the CASQ2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

Hereditary Diffuse Gastric Cancer (HDGC) is caused by pathogenic (harmful) variants in the CDH1 gene, and are linked to an increased risk for a specific type of stomach cancer called diffuse gastric cancer (also called signet ring cell carcinoma or linitis plastica), as well as lobular breast cancer. There is also some research that suggests that some families with HDGC may also have an increased risk for colon cancer.

CDH1 gene variants are inherited in an autosomal dominant pattern, meaning that children of someone who carries a pathogenic variant each have a 50% risk to inherit the variant and associated cancer risks. Notably, women and men both have the CDH1 gene and have the same chances to inherit and pass down variants in these genes. Therefore, both sides of the family are important when assessing inherited risk. However, the associated cancers and lifetime risks are different between men and women.

Genetic Testing for CDH1

Genetic testing for pathogenic variants in CDH1 are currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the CDH1 gene, but other genes known or suspected to be associated with increased cancer risks

Who should be offered testing for CDH1?
Other than someone’s personal history of cancer, another piece of information that we can use to help determine if someone is at a higher risk to have a pathogenic variant in the CDH1 gene is you family history. The National Comprehensive Cancer Network (NCCN) is a group of medical professionals that regularly meet to look over any updates in research studies and determine recommendations for who should be considered at a higher risk for one of these gene variants, and thus should be offered genetic testing.

Some of the things in the family history (make sure to include yourself in your family history if you have been diagnosed with cancer) that may put someone at a higher risk for a CDH1 pathogenic variant are:

• A family history of two people on the same side of the family diagnosed with gastric cancer, with one person being diagnosed before age 50
• A family history of three people on the same side of the family with diffuse gastric cancer at any age
• A family history of someone diagnosed with diffuse gastric cancer before the age of 40
• A family history of diffuse gastric cancer and lobular breast cancer, with one being diagnosed before age 50

These are some loose guidelines for who may be an increased risk, but a medical professional, such as a genetic counselor, will be able to meet with you to further review your family history and help determine if you meet criteria for genetic testing.

Treatment/Management for CDH1

If you are tested and found to have a pathogenic variant in the CDH1 gene, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on updated guidelines of the NCCN, but may be tailored to your specific medical and family history.

If someone is found to have a CDH1 pathogenic variant and has also been diagnosed with gastric cancer, the recommendation is to have a total gastrectomy (surgical removal of the stomach) for treatment and prevention.

If someone is found to have a CDH1 pathogenic variant and has not been diagnosed with gastric cancer, the recommendation is to consider prophylactic (preventative) gastrectomy between ages 18-40. Preventative surgery is recommended at this time because screening for diffuse gastric cancer does not always detect cancer at an early enough stage for it to be easily treatable. There are, however, significant health consequences associated with a prophylactic gastrectomy. Because of this, it is important to carefully consider all options, and to discuss the risks and benefits of the surgery with your healthcare team (which usually includes a gastroenterologist, surgeon, nutritionist, etc) to make the decision that is right for you.

If, after consideration of all of this information, the individual decides not to have the prophylactic surgery (or decides to put it off for the time being), then the recommendation would be to do an upper endoscopy with multiple random stomach biopsies every 6-12 months to look for signs of gastric cancer.

To address the higher risk of breast cancer associated with CDH1 pathogenic variants, the screening recommendations are:

• Beginning at age 18: Breast self exam to facilitate awareness and familiarity with breast tissue
• Ages 25-29: Clinical breast exam (every 6-12 months) and breast MRI (every 12 months)
• Ages 30-75: Clinical breast exam (every 6-12 months), breast MRI (every 12 months) and mammogram (every 12 months)
• Age 75+:  Individualized management; patients should work with their doctor or healthcare provider to determine the most appropriate plan

Prophylactic (preventative) mastectomies may also be considered for breast cancer prevention.

If there is a family history of colon cancer, early and more frequent colon cancer screening should be considered. Individuals with a CDH1 pathogenic variant and a family history of colon cancer should work with their doctor or healthcare provider to determine the most appropriate plan for colon cancer screening.

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

Pathogenic (harmful) variants in the CHEK2 gene have been associated with a moderately increased risk for breast cancer and colon cancer. Some studies have also suggested associated risk for other cancers, although these are not as well established.

CHEK2 pathogenic variants are inherited in an autosomal dominant pattern, meaning that children of someone who carries a pathogenic variant each have a 50% risk to inherit the variant and associated cancer risks. Notably, women and men both have the CHEK2 gene and have the same chances to inherit and pass down variants in these genes. Therefore, both sides of the family are important when assessing inherited risk. However, the associated cancers and lifetime risks are different between men and women.

Genetic Testing for CHEK2

Genetic testing for pathogenic variants in CHEK2 are currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the CHEK2 gene, but other genes known or suspected to be associated with increased cancer risks

Treatment/Management for CHEK2

If you are tested and found to have a pathogenic variant in the CHEK2 gene, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic.  General recommendations are included here based on updated guidelines of the NCCN, but may be tailored to your specific medical and family history.

For women, breast cancer screening recommendations include starting annual mammograms beginning at age 40 (or 5-10 years earlier than the youngest diagnosis in the family), and also to consider breast MRI.

Colon cancer screening recommendations for CHEK2 include colonoscopy every 5 years beginning at age 40, or if there is family history of early colon cancer in a parent or sibling, beginning 10 years prior to their age at colon cancer diagnosis, whichever is earlier.

If there is a history of other cancers in the family, your doctor or healthcare provider may recommend additional, earlier, or more frequent screening for those other cancers based on the family history.

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The COL3A1 gene makes a protein called type 3 collagen. Type 3 collagen works to strengthen and support many of the tissues in our bodies (primarily in the skin, lungs, intestines, and walls of our blood vessels).

If someone has a harmful change (called a pathogenic variant) in one of their COL3A1 genes, then their body does not make as much type 3 collagen as it should. Without enough type 3 collagen, these tissues in our bodies are not as strong and stable as they should be. This can lead different health conditions, such as the vascular form of Ehlers-Danlos syndrome, or familial thoracic aortic aneurysm and dissection.

Pathogenic variants in the COL3A1 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the COL3A1 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for COL3A1

Genetic testing for pathogenic variants in COL3A1 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the COL3A1 gene, but other genes known or suspected to be associated with cardiovascular disease or Ehlers-Danlos syndrome.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The DSC2 gene makes a protein called desmocollin-2. Our body is made up of billions of cells. Desmocollin-2 helps to make structures called desmosomes, which work to hold cells together. By doing this, they stabilize and strengthen the various different tissues that make up our bodies. Desmosomes can also help with communication within the cell. This communication helps to tell the cell when it’s time to divide to make more new cells, or when it’s time for that cell to die, which are both very important.

If someone has a harmful change (called a pathogenic variant) in one of their DSC2 genes, then their body does not make as much desmocollin-2 protein as it should. If there is not enough desmocollin-2 protein, then cells do not have as strong of a bond. This leads to a higher rate of cell death and damage because the connections between cells are not as durable. Because desmosomes help with cell communication, not having enough of them can also mean that these messages do not get delivered, which can further contribute to cell death.

This progressive cell death is what can lead to the damage in the heart muscles, which can lead to health issues, such as arrhythmogenic right ventricular cardiomyopathy and keratoderma with woolly hair.

Pathogenic variants in the DSC2 gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the DSC2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for DSC2

Genetic testing for pathogenic variants in DSC2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the DSC2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The DSG2 gene makes a protein called desmoglein 2. Our body is made up of billions of cells. Desmoglein 2 helps to make structures called desmosomes, which work to hold cells together. By doing this, they stabilize and strengthen the various different tissues that make up our bodies. Desmosomes can also help with communication within the cell. This communication helps to tell the cell when it’s time to divide to make more new cells, or when it’s time for that cell to die, which are both very important.

If someone has a harmful change (called a pathogenic variant) in one of their DSG2 genes, then their body does not make as much desmoglein 2 protein as it should. If there is not enough desmoglein 2 protein, then cells do not have as strong of a bond. This leads to a higher rate of cell death and damage because the connections between cells are not as durable. Because desmosomes help with cell communication, not having enough of them can also mean that these messages do not get delivered, which can further contribute to cell death.

This progressive cell death is what can lead to the damage in the heart muscles, which can lead to health issues such as arrhythmogenic right ventricular cardiomyopathy and familial dilated cardiomyopathy.

Pathogenic variants in the DSG2 gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the DSG2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for DSG2

Genetic testing for mutations in DSG2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the DSG2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The DSP gene makes a protein called desmoplakin. Our body is made up of billions of cells. Desmoplakin helps to make structures called desmosomes, which work to hold cells together. By doing this, they stabilize and strengthen the various different tissues that make up our bodies. Desmosomes can also help with communication within the cell. This communication helps to tell the cell when it’s time to divide to make more new cells, or when it’s time for that cell to die, which are both very important.

If someone has a harmful change (called a pathogenic variant) in one of their DSP genes, then their body does not make as much desmoplakin protein as it should. If there is not enough desmoplakin protein, then cells do not have as strong of a bond. This leads to a higher rate of cell death and damage because the connections between cells are not as durable. Because desmosomes help with cell communication, not having enough of them can also mean that these messages do not get delivered, which can further contribute to cell death.

This progressive cell death is what can lead to the damage in the heart muscles, which can lead to health issues, such as arrhythmogenic right ventricular cardiomyopathy and keratoderma with woolly hair.

Pathogenic variants in the DSP gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the DSP gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for DSP

Genetic testing for pathogenic variants in DSP is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the DSP gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The KCNH2 gene makes a protein called the KCNH2 protein that helps to build potassium channels in the body. These potassium channels allow cells to make and transmit signals which help to recharge the heart after it beats, which in turn helps to keep the heart beat at a normal rhythm. The potassium channels that are made by the KCNH2 gene are primarily in the heart muscles.

If someone has a harmful change (called a pathogenic variant) in one of their KCNH2 genes, then their body is not going to make enough of the KCNH2 protein as it should. If there is not enough KCNH2 protein, then there will not be enough potassium channels. This would mean that the heart’s ability to send these signals is not going to work as well as it should. This can lead to several different types of health concerns, including Long QT syndrome and familial atrial fibrillation.

Pathogenic variants in the KCNH2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the KCNH2 gene and have the same chances to inherit and pass down pathogenic variants.

If someone inherits a pathogenic variant from BOTH of their parents, they have zero working KCNH2 genes. This can cause an autosomal recessive condition called Jervell and Lange-Nielsen syndrome, which causes Long QT syndrome and profound hearing loss from birth. Approximately 10 percent of cases of Jervell and Lange-Nielsen syndrome are caused by non working KCNH2, while the rest are caused by non working KCNQ1 genes.

Genetic Testing for KCNH2

Genetic testing for pathogenic variants in KCNH2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the KCNH2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The KCNQ1 gene makes a protein called the KCNQ1 protein that helps to build potassium channels in the body. These potassium channels allow cells to make and transmit signals which help to recharge the heart after it beats, which in turn helps to keep the heart beat at a normal rhythm. The potassium channels that are made by the KCNQ1 gene are primarily in the heart muscles and the tissue in the inner ear (which helps with our hearing).

If someone has a harmful change (called a pathogenic variant) in one of their KCNQ1 genes, then their body is not going to make enough of the KCNQ1 protein as it should. If there is not enough KCNQ1 protein, then there will not be enough potassium channels. This would mean that the heart’s ability to send these signals is not going to work as well as it should. This can lead to several different types of health concerns, including Long QT syndrome and familial atrial fibrillation.

Pathogenic variants in the KCNQ1 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the KCNQ1 gene and have the same chances to inherit and pass down pathogenic variants.

If someone inherits a pathogenic variant from BOTH of their parents, they have zero working KCNQ1 genes. This can cause an autosomal recessive condition called Jervell and Lange-Nielsen syndrome, which causes Long QT syndrome and profound hearing loss from birth. Ninety percent of cases of Jervell and Lange-Nielsen syndrome are caused by non working KCNQ1, while the rest are caused by non working KCNH2 genes.

Genetic Testing for KCNQ1

Genetic testing for pathogenic variants in KCNQ1 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the KCNQ1 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The LDLR gene makes a protein called a low-density lipoprotein receptor (LDL-r). This LDL-r attaches to LDL cholesterol that is floating around in our blood and brings it into our cells. Our cells can then either use, store, or get rid of the cholesterol.

The LDL-r protein is most active in the liver, which is the organ that removes most of the extra cholesterol in our bodies. The amount of the LDL-r protein in the liver determines how fast the liver can remove extra cholesterol from the bloodstream. If there is a harmful error (called a pathogenic variant) in the LDLR gene, then it may not make as much of the LDL-r protein as the body needs. If there is not enough of the LDL-r protein, then the liver can not clear extra cholesterol from the bloodstream as quickly. This can lead to the cholesterol building up in the body, which can cause the signs and symptoms we associate with familial hypercholesterolemia.

Recent studies have shown that only approximately 73% of people who carry a pathogenic variant in the LDLR gene have significantly elevated LDL cholesterol level. This means that some individuals in the family may carry this variant, and could potentially pass it down to their children, but have no obvious signs or symptoms.

Pathogenic variants in the LDLR gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the LDLR gene and have the same chances to inherit and pass down pathogenic variants. Almost all people who have a pathogenic variant in the LDLR gene have a parent who also carries it.

Genetic Testing for LDLR

Genetic testing for pathogenic variants in LDLR is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the LDLR gene, but other genes known or suspected to be associated with familial hypercholesterolemia

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The LMNA gene makes proteins called lamins. Our body is made up of billions of cells, and there are many parts of the cell. The ‘mothership’ of the cell is called the nucleus. The nucleus holds our DNA and helps to protect and regulate it. The nuclear envelope surrounds the nucleus to help protect it, and to monitor different things that travel in and out of the nucleus. Lamins work to support the nuclear envelope and make sure that the nucleus is protected. Some studies have also suggested that lamins may play a part in how our genes are expressed.

If someone has a harmful change (called a pathogenic variant) in one of their LMNA genes, then their body does not make as much lamin protein as it should. If there is not enough lamin protein, then the nucleus is not as well protected. This leads to a higher rate of cell death and damage because the nucleus of the cells are more vulnerable. This progressive cell death is what can damage the heart muscles, which can lead to several different types of health issues, including arrhythmogenic right ventricular cardiomyopathy, familial dilated cardiomyopathy, and left ventricular noncompaction.

Pathogenic variants in the LMNA gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries a pathogenic variant has a 50% chance to pass it down to any children they have. Women and men both have the LMNA gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for LMNA

Genetic testing for pathogenic variants in LMNA is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the LMNA gene, but other genes known or suspected to be associated with hereditary heart disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

Individuals with MUTYH-Associated Polyposis syndrome (MAP) have a high lifetime risk for colon polyps and colon cancer. There are usually tens to hundreds of polyps found in the large intestine, but some people may develop colon cancer without polyps.

Pathogenic (or harmful) variants in the MUTYH gene cause MAP. MAP is inherited in an autosomal recessive pattern, meaning that each of someone’s parents carry a pathogenic variant in the MUTYH gene, and both parents pass that pathogenic variant down to a child. Two people who carry pathogenic variants in the MUTYH gene have a 25% chance for each of their children to have MAP. Notably, women and men both have the MUTYH gene and have the same chances to inherit and pass down variants in this gene. Therefore, both sides of the family are important when assessing inherited risk.

Individuals with MAP are also at increased risk of:

• Polyps in the stomach and small intestine
• Spots, like freckles, on the inside of your eye called CHRPE
• Cysts in your jaw bone, liver, or kidney
• Fatty tumors, called subcutaneous lipomas
• Other tumors of the skin that can start in the glands or different skin layers, called sebaceous gland adenomas or epitheliomas

Genetic Testing for MUTYH

Genetic testing is available for this condition. This can be done on a blood or saliva sample. The results take about 3 weeks to return. There are different ways to complete this testing. This can include:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include MUTYH gene, but other genes known or suspected to be associated with colon polyps and increased cancer risks

Those who undergo testing for the MUTYH gene due to a personal history of many colon polyps should also be offered testing for another genetic predisposition to colon polyps called Familial Adenomatous Polyposis (FAP). These two conditions are caused by pathogenic variants in two separate genes but it is often difficult to distinguish between the two conditions without genetic testing.

Who should be offered testing for MUTYH?
The National Comprehensive Cancer Network (NCCN) is a group of medical professionals that regularly meet to look over any updates in research studies and determine recommendations for who should be considered at a higher risk for one of these gene variants, and thus should be offered genetic testing:

• Personal history of at least 20 adenomatous colon polyps. Testing can be considered if 10-20 polyps found.
• Family history of a known MUTYH pathogenic variant, or a family member has a positive test result.
• Those with serrated polyposis syndrome and have at least five adenomatous polyps. There is no clear genetic cause for serrated polyposis syndrome, but testing for MUTYH can be done, especially with a personal history of adenomas along with the serrated polyps.

Treatment/Management for MUTYH

If you are tested and found to have MUTYH/MAP, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on the updated guidelines of the NCCN, but may be tailored to your specific medical and family history.  

For individuals with MAP who have not had polyps; or for siblings of people with MAP who have not had testing themselves:

• Colonoscopy starting at age 25-30, continuing every 2-3 years if no symptoms. If polyps discovered, go to plan below.
• Annual physical exam.
• Baseline endoscopy at 30-35.

For individuals with MAP who have already had polyps:

• Younger than 21: colonoscopy every 1-2 years. Surgery can be considered if too many polyps.
• 21 or older, with manageable polyp burden: colonoscopy every 1-2 years. Consider surgical evaluation and colectomy as appropriate
• Too many polyps to handle endoscopically: consider surgery. Exact type should be discussed with physician.
• Annual physical exam.
• Baseline endoscopy at 30-35.

Associated Conditions of MUTYH: MUTYH Associated Polyposis (MAP)

Individuals who carry one pathogenic variant in the MUTYH gene are considered carriers for MAP. One to two percent of the general population are thought to be carriers for MAP. Some studies have shown that carriers for MAP may have a slightly increased risk for colon cancer, but specific numbers are not currently available. The National Comprehensive Cancer Network recommends that if someone is a carrier for MAP and they have a first-degree relative (parent, sibling, child) with colorectal cancer, they should start colonoscopy screening at age 40 (or 10 years prior to the age of the first-degree relative’s age at diagnosis, whichever is earlier). If the colonoscopy is normal, it should be repeated every 5 years.

There are currently no specific data available to determine whether specialized screening is needed for individuals who are carriers for MAP who do not have a first-degree relative with colorectal cancer, and the plan for screening should be discussed with a primary care provider. In the general population, colon cancer screening is recommended to begin at age 50 (with no genetic risk factors or family history of colorectal cancer).

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MYBPC3 gene makes a protein called cardiac myosin binding protein C (MyBP-C). Our muscles, including our heart muscles, are made up of different fibers that help to control when our muscles contract. This process is necessary in our heart, because these contractions are how our heart pumps blood throughout our bodies. The cardiac MyBP-C protein works to keep these fibers in good working order so they can make sure our heart muscles are contracting how they should.

If someone has a harmful change (called a pathogenic variant) in one of their MYBPC3 genes, then their body does not make as much MyBP-C protein as it should. If there is not enough MyBP-C protein, then the fibers that control our heart contractions may get damaged. This damage is what can lead to several different types of health issues, including left ventricular noncompaction, familial hypertrophic cardiomyopathy, and familial dilated cardiomyopathy.

Pathogenic variants in the MYBPC3 gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries a pathogenic variant has a 50% chance to pass it down to any children they have. Women and men both have the MYBPC3 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for MYBPC3

Genetic testing for pathogenic variants in MYBPC3 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MYBPC3 gene, but other genes known or suspected to be associated with hereditary heart disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MYH7 gene makes a protein called beta (β)-myosin heavy chains (β-myosin). The β-myosin protein is most active in the heart and skeletal muscles (which help with movement) in our body. The β-myosin protein works with other proteins to create the force that is needed for our muscles to contract. This muscle contraction is how we move, and is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their MYH7 genes, then their body does not make as much β-myosin protein as it should. If there is not enough β-myosin protein, then the skeletal and cardiac muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, left ventricular noncompaction, and familial dilated cardiomyopathy.

Pathogenic variants in the MYH7 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the MYH7 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for MYH7

Genetic testing for pathogenic variants in MYH7 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MYH7 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MYH11 gene makes a protein called smooth muscle myosin heavy chain 11 (MYH11 protein). The MYH11 protein is found primarily in our smooth muscles (muscles that line our blood vessels, stomach, intestines, and other internal organs). Smooth muscles relax and contract automatically as part of their normal function, and the MYH11 protein works with other proteins to help the smooth muscles contract, which helps them to keep their shape instead of stretching out too much while blood is pumping through.

If someone has a harmful change (called a pathogenic variant) in one of their MYH11 genes, then their body does not make as much MYH11 protein as it should. If there is not enough MYH11 protein, then the smooth muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to health issues like familial thoracic aortic aneurysm and dissection along with a congenital (from birth) heart defect called patent ductus arteriosus.

Pathogenic variants in the MYH11 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the MYH11 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for MYH11

Genetic testing for pathogenic variants in MYH11 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MYH11 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MYL2 gene makes a protein called beta (β)-myosin heavy chains (β-myosin). The β-myosin protein is most active in the heart and skeletal muscles (which help with movement) in our body. The β-myosin protein works with other proteins to create the force that is needed for our muscles to contract. This muscle contraction is how we move, and is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their MYL2 genes, then their body does not make as much β-myosin protein as it should. If there is not enough β-myosin protein, then the skeletal and cardiac muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to familial hypertrophic cardiomyopathy.

Pathogenic variants in the MYL2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the MYL2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for MYL2

Genetic testing for pathogenic variants in MYL2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MYL2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The MYL3 gene makes a protein called the myosin light chain 3 (MLC3) protein. The MLC3 protein is found primarily in the heart muscles in our body. The MLC3 protein works with other proteins to create the force that is needed for our heart muscles to contract. This muscle contraction is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their MYL3 genes, then their body does not make as much MLC3 protein as it should. If there is not enough MLC3 protein, then the heart muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to familial hypertrophic cardiomyopathy.

Pathogenic variants in the MYL3 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the MYL3 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for MYL3

Genetic testing for pathogenic variants in MYL3 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the MYL3 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. Our cells are constantly dividing to make new cells, and to do that the cell has to make a copy of all of its DNA, which is what our genes are made out of. As this copying process happens, there can be errors (called variants) that happen in our DNA. Having these variants build up in our DNA raises the risk for cancer. The NBN gene makes a protein called nibrin. Nibrin works with other proteins to help repair these errors in our DNA. If someone has a non-working copy of the NBN gene, then their cells lose the ability to fix these errors in our DNA, which can then increase the risk to develop cancer.

NBN pathogenic (harmful) variants related to cancer risk are inherited in an autosomal dominant pattern, meaning that children of someone who carries a pathogenic variant each have a 50% risk to inherit the variant and associated cancer risks. Notably, women and men both have the NBN gene and have the same chances to inherit and pass down variants in these genes. Therefore, both sides of the family are important when assessing inherited risk.

Genetic Testing for NBN

Genetic testing for pathogenic variants in NBN are currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the NBN gene, but other genes known or suspected to be associated with increased cancer risks

Treatment/Management for NBN

If you are tested and found to have a pathogenic variant in the NBN gene, it is recommended to discuss your management plan with your healthcare team, and if available, to see consultation through a specialized high-risk clinic. General recommendations are included here based on updated guidelines of the National Comprehensive Cancer Network (NCCN), but may be tailored to your specific medical and family history.

Women who carry a pathogenic variant in the NBN gene should consider annual mammography and breast MRI starting at the age of 40, or 5-10 years before the earliest age of diagnosis of breast cancer in the family.

One important thing to note is that the data on how the NBN gene affects cancer risk is still limited, and more research is needed to completely understand the lifetime risks for cancers associated with inherited pathogenic variants in this gene. There have thus far been a limited number of research studies, and some of those studies have had a small number of participants, or participants from a specific ethnic group.

Men who have inherited a NBN pathogenic variant may be at a slightly increased risk for prostate cancer, but there is not enough data to say for certain what the level of risk is, and there are no current recommendations for increased prostate cancer screening different from that of the general population. Further research about the NBN gene is expected to be available in the coming years, so recommendations may evolve.

Associated Conditions of NBN: Nijemegan Breakage Syndrome

If someone inherits copies of the NBN gene that both have pathogenic variants in them (one from each parent), this can lead to a condition called Nijemegan Breakage Syndrome (NBS). NBS is a very rare autosomal recessive condition involving a variety of developmental abnormalities including microcephaly (small head size), immune deficiency, and an increased risk leukemia or lymphoma. When an individual and her/his partner both carry an NBN pathogenic variant, their chance to have a child affected with NBS is 25%. For family planning purposes, genetic counseling regarding NBS may be considered for individuals of reproductive age in at-risk families.

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

Pathogenic (or harmful) variants in the PALB2 gene have been associated with increased risk for breast cancer. Other cancer risks associated with pathogenic variants in PALB2 have not been fully established, but studies have suggested increased risks for pancreatic cancer, ovarian cancer, and male breast cancer.

PALB2 pathogenic variants are inherited in an autosomal dominant pattern, meaning that children of someone who carries a pathogenic variant each have a 50% risk to inherit the variant and associated cancer risks. Notably, women and men both have the PALB2 gene and have the same chances to inherit and pass down variants in these genes. Therefore, both sides of the family are important when assessing inherited risk.

Genetic Testing for PALB2

Genetic testing for pathogenic variants in PALB2 are currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the PALB2 gene, but other genes known or suspected to be associated with increased cancer risks

Treatment/Management for PALB2

If you are tested and found to have a pathogenic variant in the PALB2 gene, it is recommended to discuss your management plan with your healthcare team, and if available, to seek consultation through a specialized high-risk clinic. General recommendations are included here based on updated guidelines of the NCCN, but may be tailored to your specific medical and family history.

For women, breast cancer screening recommendations include starting annual mammograms at age 30 with consideration of breast MRI starting at age 30, or 5-10 years prior to the earliest diagnosis of breast cancer in the family, whichever is earlier.

Screening or preventative guidelines for other cancer risks possibly associated with PALB2 pathogenic variants are not clearly established. If there is a history of other cancers in the family, your doctor or healthcare provider may recommend additional, earlier, or more frequent screening for other cancers based on the family history.

Associated Conditions of PALB2: Fanconi Anemia

The above information about cancer risks is relevant for people who have a single pathogenic variant in the PALB2 gene. Importantly, if a child inherits pathogenic variants in both copies the PALB2 gene (one pathogenic variant from mom and one pathogenic variant from dad), this causes a different genetic condition called Fanconi anemia. Fanconi anemia is a rare condition associated with defects of the bone marrow, increased risks for other cancers (e.g. leukemia), as well as some birth defects. Therefore, people with a PALB2 pathogenic variant who are pregnant or planning to have children are recommended to seek genetic counseling to clarify the risk to their children.

Click here to learn more about scheduling a genetic counseling appointment for questions about hereditary cancer predisposition.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The PCSK9 gene makes a protein called the PCSK9 protein. The PCSK9 protein helps to regulate the amount of cholesterol that is the bloodstream by controlling the number of LDL cholesterol receptors on the cells. LDL receptors attach to LDL cholesterol that is floating around in the blood and brings it into the cells. The cells can then either use, store, or get rid of the cholesterol. The number of LDL receptors that a cell has determines how quickly LDL cholesterol is removed from the bloodstream.

If there is a harmful error (called a pathogenic variant) in the PCSK9 gene, then it may not make as much of the PCSK9 protein as the body needs. If there is not enough of the PCSK9 protein, then the liver can not clear extra cholesterol from the bloodstream as quickly. This can lead to the cholesterol building up in the body, which can cause the signs and symptoms we associate with familial hypercholesterolemia.

Pathogenic variants in the PCSK9 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the PCSK9 gene and have the same chances to inherit and pass down pathogenic variants. Almost all people who have a pathogenic variant in the PCSK9 gene have a parent who also carries it.

Genetic Testing for PCSK9

Genetic testing for pathogenic variants in PCSK9 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the PCSK9 gene, but other genes known or suspected to be associated with familial hypercholesterolemia

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The PKP2 gene makes a protein called plakophilin 2. Our body is made up of billions of cells. Plakophilin 2 helps to make structures called desmosomes, which work to hold cells together. By doing this, they stabilize and strengthen the various different tissues that make up our bodies. Desmosomes can also help with communication within the cell. This communication helps to tell the cell when it’s time to divide to make more new cells, or when it’s time for that cell to die, which are both very important.

If someone has a harmful change (called a pathogenic variant) in one of their PKP2 genes, then their body does not make as much plakophilin 2 protein as it should. If there is not enough plakophilin 2 protein, then cells do not have as strong of a bond. This leads to a higher rate of cell death and damage because the connections between cells are not as durable. Because desmosomes help with cell communication, not having enough of them can also mean that these messages do not get delivered, which can further contribute to cell death.

This progressive cell death is what can lead to the damage in the heart muscles, which can lead to health issues, such as arrhythmogenic right ventricular cardiomyopathy.

Pathogenic variants in the PKP2 gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the PKP2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for PKP2

Genetic testing for pathogenic variants in PKP2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the PKP2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The PRKAG2 gene makes part of a protein called AMP-activated protein kinase (AMPK). The AMPK protein works in many parts of our bodies, particularly in the heart and skeletal muscles (which help with movement), and monitors if our cells need more energy. Our cells break down a molecule called adenosine triphosphate (ATP), and that is what they use for energy to keep functioning how they should. The AMPK protein helps to control the amount of ATP is broken down to make sure the cell has enough energy to do its job.

If someone has a harmful change (called a pathogenic variant) in one of their PRKAG2 genes, then their body does not make as much AMPK protein as it should. If there is not enough AMPK protein, then the amount of ATP that is available to the cells for energy is not as high as it should be. This can lead to the cells not being able to perform their functions, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, and familial atrial fibrillation.

Pathogenic variants in the PRKAG2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the PRKAG2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for PRKAG2

Genetic testing for pathogenic variants in PRKAG2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the PRKAG2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The RYR2 gene makes a protein called ryanodine receptor 2. The ryanodine receptor 2 protein helps to form channels to move calcium between cells. These calcium channels allow cells to make and transmit signals which help to make the heartbeat at a normal rhythm. The calcium channels that are made by the RYR2 gene are primarily in the heart muscles.

If someone has a harmful change (called a pathogenic variant) in one of their RYR2 genes, then their body is not going to make enough of the ryanodine receptor 2 protein as it should. If there is not enough ryanodine receptor 2 protein, then there will not be enough calcium channels. This would mean that the heart’s ability to send these signals is not going to work as well as it should. This can lead to a heart condition called catecholaminergic polymorphic ventricular tachycardia.

Pathogenic variants in the RYR2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the RYR2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for RYR2

Genetic testing for pathogenic variants in RYR2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the RYR2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The SCN5A gene makes a protein called the SCN5A (or sodium voltage-gated channel alpha subunit 5) protein that helps to build sodium channels in the body. These sodium channels allow cells to make and transmit signals which help to make the heart beat at a normal rhythm. The sodium channels that are made by the SCN5A gene are primarily in the heart muscles.

If someone has a harmful change (called a pathogenic variant) in one of their SCN5A genes, then their body is not going to make enough of the SCN5A protein as it should. If there is not enough SCN5A protein, then there will not be enough sodium channels. This would mean that the heart’s ability to send these signals is not going to work as well as it should. This can lead to several different types of heart conditions, including Brugada syndrome, familial dilated cardiomyopathy, Romano-Ward syndrome (a common type of Long QT syndrome), and left ventricular noncompaction.

Pathogenic variants in the SCN5A gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the SCN5A gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for SCN5A

Genetic testing for pathogenic variants in SCN5A is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the SCN5A gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The TMEM43 gene makes a protein called a nuclear envelope protein. Our body is made up of billions of cells, and there are many parts of the cell. The ‘mothership’ of the cell is called the nucleus. The nucleus holds our DNA and helps to protect and regulate it. Nuclear envelope proteins surround the nucleus to help protect it, and to monitor different things that travel in and out of the nucleus.

If someone has a harmful change (called a pathogenic variant) in one of their TMEM43 genes, then their body does not make as much nuclear envelope protein as it should. If there is not enough nuclear envelope protein, then the nucleus is not as well protected. This leads to a higher rate of cell death and damage because the nucleus of the cells are more vulnerable. This progressive cell death can cause damage to the muscles, which can lead to different types of health issues, such as arrhythmogenic right ventricular cardiomyopathy or Emery-Dreifuss muscular dystrophy.

Pathogenic variants in the TMEM43 gene are passed through the family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the TMEM43 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for TMEM43

Genetic testing for pathogenic variants in TMEM43 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the TMEM43 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The TNNI3 gene makes a protein called the cardiac troponin 1 protein. The cardiac troponin 1 protein is found primarily in the heart muscles in our body. The cardiac troponin 1 protein works with other proteins to create the force that is needed for our muscles to contract. This muscle contraction is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their TNNI3 genes, then their body does not make as much cardiac troponin 1 protein protein as it should. If there is not enough cardiac troponin 1 protein protein, then the heart muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, familial restrictive cardiomyopathy, and familial dilated cardiomyopathy.

Pathogenic variants in the TNNI3 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the TNNI3 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for TNNI3

Genetic testing for pathogenic variants in TNNI3 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the TNNI3 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The TNNT2 gene makes a protein called cardiac troponin T. The cardiac troponin T protein is found primarily in the heart muscles in our body. The cardiac troponin T protein works with other proteins to create the force that is needed for our heart muscles to contract. This muscle contraction is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their TNNT2 genes, then their body does not make as much cardiac troponin T protein as it should. If there is not enough cardiac troponin T protein, then the heart muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, left ventricular noncompaction, and familial dilated cardiomyopathy.

Pathogenic variants in the TNNT2 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the TNNT2 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for TNNT2

Genetic testing for pathogenic variants in TNNT2 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the TNNT2 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.

We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The TPM1 gene makes a protein called the tropomyosin 1 (T1) protein. The T1 protein is most active in the heart and skeletal muscles (which help with movement) in our body. The T1 protein works with other proteins to create the force that is needed for our muscles to contract. This muscle contraction is how we move, and is how our heart pumps blood throughout our bodies.

If someone has a harmful change (called a pathogenic variant) in one of their TPM1 genes, then their body does not make as much T1 protein as it should. If there is not enough T1 protein, then the skeletal and cardiac muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to several different types of health issues, such as familial hypertrophic cardiomyopathy, left ventricular noncompaction, and familial dilated cardiomyopathy.

Pathogenic variants in the TPM1 gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the TPM1 gene and have the same chances to inherit and pass down pathogenic variants.

Genetic Testing for TPM1

Genetic testing for pathogenic variants in TPM1 is currently available, but there are a few different ways to approach testing:

• Single site analysis: Testing specific to a known pathogenic variant in the family
• Full gene sequencing and rearrangement analysis: Comprehensive testing to search for all currently detectable pathogenic variants in the gene
• Gene panels: Newer, more broadly based gene tests that would include not only the TPM1 gene, but other genes known or suspected to be associated with hereditary cardiovascular disease.

Click here to learn more about scheduling a genetic counseling appointment for questions about pediatric or adult genetic conditions.