Mount Elizabeth Novena Centre for Genomic Health

What is familial hypercholesterolemia?

Familial hypercholesterolaemia (FH) is an inherited condition caused by a genetic mutation leading to high blood cholesterol levels, specifically in low-density lipoprotein (LDL) cholesterol. FH is one of the most common inherited conditions, affecting about 1 in 250 people. It brings with it a heightened risk of early cardiovascular disease.

Am I, or is my family at risk for familial hypercholesterolemia?

Your risk for FH may be higher if:

• There is a history of early cardiovascular disease in close family members
• You are a male and have had a heart attack before the age of 50, or female and have had a heart attack before the age of 60
• Your LDL cholesterol is very high (≥160 mg/dL for children or 190 mg/dL for adults)
• Other family members have been diagnosed with FH
• You have physical signs of high cholesterol, such as swollen tendons on the heels and knuckles of the hands (tendon xanthoma), yellowish patches around the eyes (xanthelasma), or a white deposit of cholesterol in the shape of an arc (corneal arcus) at the edge of the coloured part of the eye

What can clinical familial hypercholesterolemia genetic testing do?

Clinical FH genetic testing can help:

• Confirm a FH diagnosis. The test looks for a “disease-causing” alteration in the LDL receptor, APOB, PCSK9 or APOE genes.
• Prevent cardiovascular disease. If you are diagnosed with FH, there is a 50% chance your family members (parents, brothers, sisters, and children) may have FH, and genetic testing is also recommended for them. This form of testing is known as cascade predictive testing – a way to find FH before it leads to cardiovascular issues.
• Understand the precise cause of your high cholesterol levels
• Prevent coronary artery disease (CAD) events. Your test results can help empower healthcare professionals to prescribe effective treatments early.

What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy is among the most common inherited heart diseases, affecting about 1 in 500 to 1 in 1000 people. This disease is characterised by an abnormal thickening in the wall of the left ventricle (called left ventricular hypertrophy), the heart's main pumping chamber.

As a result, the heart muscle may become stiff, making it difficult to relax. This will cause the heart to require higher pressure than normal to fill, leading to shortness of breath, chest pain and dizziness.

Am I, or is my family at risk for hypertrophic cardiomyopathy?

It is important to ask close and extended family members if there are any cases of heart problems, sudden death, unexplained deaths and/or major health problems in the family.

What can clinical hypertrophic cardiomyopathy genetic testing do?

Clinical hypertrophic cardiomyopathy genetic testing can help to:

• Confirm a diagnosis of the disease
• Provide insights on underlying causes
• Identify at-risk family members for cascade screening
• Help begin risk reduction interventions by allowing you and your doctor to make informed medical decisions

What is Marfan syndrome?

Marfan syndrome (MS) is a connective tissue disorder caused by FBN1 gene mutations on chromosome 15 – a chromosome that produces a vital connective tissue protein.

This disease doesn't impact intelligence but can affect the heart, blood vessels, bones, joints, eyes, and sometimes the lungs and skin. A pregnancy with MS can pose risks, especially if the aortic root exceeds 4cm.

Am I, or is my family at risk for Marfan syndrome?

MS is more likely if one or more of the following features can be confirmed in your family:

• You have close blood relatives such as parents, siblings, or grandparents, who have been diagnosed with MS
• There is a pattern of MS occurring across multiple generations within your family
• There is a consistent presence of MS-related traits among your family members, such as tall stature, joint hypermobility, or eye abnormalities
• A specific genetic mutation associated with MS has been identified in your family
• You have relatives who have been diagnosed with other connective tissue disorders, such as Ehlers-Danlos syndrome or Loeys-Dietz syndrome

What can clinical Marfan syndrome genetic testing do?

Clinical MS genetic testing can help to:

• Confirm a diagnosis of the disease
• Provide insights on any underlying causes of heart disease
• Identify at-risk family members for cascade screening
• Kickstart risk reduction interventions by helping you and your doctor make informed medical decisions

What is hereditary breast and ovarian cancer syndrome?

HBOC is an inherited genetic condition, and there are 2 primary genes linked with most families who have HBOC – BRCA1 and BRCA2. A mutation in either of these genes increases a woman's lifetime risk of developing breast and ovarian cancers.

Men with these gene mutations also have an increased risk of breast and prostate cancer. These genetic mutations can also cause a slight increase in the risk of other cancers, including pancreatic cancer and melanoma.

Am I, or is my family at risk for hereditary breast and ovarian cancer syndrome?

About 5 – 10% of breast cancers and 15 – 20% of ovarian cancers can be attributed to HBOC.

The chance that a family has HBOC increases in any of these situations:

• 1 or more women are diagnosed with breast and ovarian cancer at age 50 or younger
• 1 or more women are diagnosed with breast cancer before age 50 with an additional family history of cancer, such as prostate cancer, melanoma, and pancreatic cancer
• There are breast and/or ovarian cancers in multiple generations on the same side of the family, such as having both a grandmother and an aunt on the father’s side both diagnosed with these cancers
• A woman is diagnosed with a second breast cancer in the same or the other breast or has both breast and ovarian cancers
• A male relative is diagnosed with breast cancer
• There is a history of breast cancer, ovarian cancer, prostate cancer, and/or pancreatic cancer on the same side of the family

What can clinical hereditary breast and ovarian cancer syndrome genetic testing do?

Clinical HBOC genetic testing can help:

• Provide critical insights into your risk of developing breast and ovarian cancer due to inherited genetic mutations, like those in the BRCA1 and BRCA2 genes.
• Potentially improve treatment outcomes and increase survival rates. Your test results can help your doctor establish personalised cancer treatment or prevention and early detection plans.
• Inform your family members about their own risk. This can facilitate proactive measures and potentially reduce the overall burden of these cancers in your family.

What is Lynch syndrome?

Lynch syndrome is the most common form of hereditary colorectal cancer in Singapore. Those with Lynch syndrome also have an increased risk of developing other cancers such as endometrial (uterine) cancer, stomach cancer, breast cancer, and pancreatic cancer.

It is estimated that 1 in 300 people may be carriers of a gene mutation associated with Lynch syndrome, placing it among the most common hereditary cancer syndromes.

Am I, or is my family at risk for Lynch syndrome?

The history of cancer in your close relatives can provide hints about your family’s chance of having Lynch syndrome. Close relatives include children, siblings, parents, aunts, uncles, grandchildren and grandparents on one side of the family.

Lynch syndrome is more likely if one or more of the following features can be confirmed in your family:

• A relative was diagnosed with colorectal cancer at age 50 or younger
• A relative has been diagnosed with colorectal cancer and another Lynch syndrome cancer, with one of the cancers diagnosed at age 50 or younger
• 2 close family members have been diagnosed with a Lynch syndrome cancer at age 50 or younger
• 3 close family members (over more than 1 generation) have been diagnosed with a Lynch syndrome cancer, including at least 1 case of colorectal cancer and at least 1 cancer diagnosed at age 50 or younger
• An abnormal immunohistochemistry (IHC) or microsatellite instability (MSI) result in tumour tissues. IHC and MSI results are derived from screening tests performed on tumour tissues to help determine if Lynch syndrome is likely.

What can clinical Lynch syndrome genetic testing do?

Clinical Lynch syndrome genetic testing can help to:

• Identify individuals with an increased risk of hereditary colorectal cancer and other associated cancers.
• Improve the chances of early cancer detection and successful treatment. Detecting this genetic mutation allows for early intervention and tailored cancer screening.
• Enable family members to assess their own risk, offering them the opportunity for proactive monitoring and preventive measures.