A mutation in a key gene, when it is passed from generation to generation (a germline mutation) can cause an Inherited Cancer Syndrome.
This page contains a list of the most common, well described syndromes and their associated genes.

Some Hereditary Cancer Syndromes have a strong phenotype (a “look”).
For example, Peutz Jeghers syndrome is associated with very obvious freckles on the lips and inside the mouth.
The Hereditary Breast and Ovarian Cancer syndrome (which Angelina Jolie made so famous and which, by the way, also increases prostate cancer risk) doesn’t have any particular facial or skin features. Instead, we rely on the type of cancer, age of onset or just the number of cancers in a family to determine who would benefit from genetic testing.

Click on the syndrome you are interested in to see a brief summary. Then, follow the links.

• The US National Library of Medicine’s Genetics Home Reference site covers more than 1100 syndromes and health conditions and more that 1300 genes!
• The Cancer Institute’s eviQ pages at www.eviQ.org.au provide accurate management and testing guidelines. We haven’t provided a link as the site requires a password. It’s open to patients and doctors: they just ask that you register so that they can track usage. Once on the site, look under Cancer Genetics in the left hand Category Menu
• Lastly, we provided some of the best Support Group pages relating to this condition for individuals and families.

For general information on Cancer and support services, the Cancer Council and Rare Cancers Australia are good resources.

Please tell us about any “broken links” you come across. We try our very best to make sure this information is accurate, current and helpful. Also, if you find something that you or your family found particularly useful, let us know.

We have not tried to reproduce detailed descriptions or management advice. Instead we have provided a summary with links to other quality resources.

Anybody who is concerned about their own risk or their family’s risk of cancer can see a Cancer Genetics Specialist such as a Genetic Oncologist. You don’t need to have had cancer yourself.

Sydney Cancer Genetics is a private, specialised medical service supporting individuals and families concerned about cancer.
We provide genetic counselling and genetic testing (including BRCA1 and BRCA2).
Our staff includes Genetic Oncologist Dr Hilda High. Dr High sees patients throughout Australia via bulk billed Telehealth and face to face in Sydney from rooms in Wahroonga and Ultimo. Dr High is an unpaid director of The Cancer Genetics Fund. She is passionately committed to increasing awareness of Hereditary Cancer Syndromes and ensuring all Australians have access to research and support regardless of where they live.

For a list of both public hospital based familial cancer clinics and other private cancer genetics services see The Human Genetics Society of Australasia.

Ataxia-Telangiectasia syndrome is rare, affecting 1 in 40,000 to 100,000 people worldwide.

It occurs when an individual inherits mutations in the ATM gene from both their mother and their father (autosomal recessive). It causes severe disability and is usually diagnosed in early childhood. It is characterised by poor co-ordination and balance (“ataxia”) and small clusters of enlarged blood vessels that are red or purple and often spidery in appearance and are seen in the eyes and on the skin (“telangiectasia”). The immune system may also be affected.

When an individual inherits only one copy of the ATM gene with a mutation, the syndrome doesn’t occur. However, the lifetime risk of breast cancer increases. With one a specific ATM c.7271T>G mutation, the lifetime risk of breast cancer is high (similar to that associated with a germline BRCA2 gene mutation).

There is a 50% chance of a person who carries a germline ATM c.7271T>G mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early.

• The US Genetics Home Reference site has information on the condition, how it is inherited as well as management advice.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for women who carry the ATM (c.7271T>G) mutation. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• BrAsh AT is a support group for individuals and families affected by Ataxia-Telangiectasia. It is based in Queensland but runs activities throughout Australia.

Familial Adenomatous Polyposis (FAP), as the name suggests, causes polyps. It affects 1 in 7,000 to 1 in 22,000 people.

In the classic form, 100 to 1000s of polyps develop in the colon. The polyps start appearing in the early teens and left untreated these polyps almost always become cancerous. The classical form is associated with a phenotype that includes desmoids, cysts in the jaw (osteomas), harmless changes in the eye (CHRPE) and polyps elsewhere in the gastrointestinal tract.

There is also a milder form called attenuated FAP (AFAP). Here, 10s to 100s of polyps develop, usually appearing at a later age and there are usually no other signs or symptoms.

This syndrome has also been called Gardner syndrome in the past.

There is a 50% chance of a person who carries an APC germline mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for blood relatives. For relatives who carry a mutation, screening starts around age 12.

There’s lots that can be done to reduce risk. For more information, see the links below

• The Centre for Genetic Education fact sheet on Hereditary Bowel Cancer.
• The US National Library of Medicine’s Genetics Home Reference page on Familial Adenomatous Polyposis
• You may also find the Cancer Institutes FAP brochure useful, although the eviQ page provides the most up to date screening and testing advice.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• FAP Gene Support Group is based in the UK
• We haven’t found a specific Australian Support Group for this syndrome yet. If you know of one, please tell us!

Paediatric diagnosis. Not discussed in detail at this time

Birt Hogg Dubé syndrome (BHD) is an inherited syndrome caused by a mutation in the Folliculin gene (FLCN). It is very rare, with around 400 families known worldwide.

It is associated with a small skin coloured lumps on the face and chest (benign skin tumours called fibrofolliculoma). These appear in the 20s. Individuals with BHD have a high chance of developing cysts in  the lungs and the kidneys. Kidney tumours  occur in 20 to 30% of individuals.  These tend to be bilateral, multifocal and slow growing. In some cases these tumours may develop into cancers.

The severity of the signs and symptoms vary among affected individuals, even within families, and is not predictable.

Because of the risk of pneumothorax, a medicalert bracelet should be worn. Smoking and scuba diving (due to high ambient pressures) should be avoided.

Screening for renal tumours should start at age 20 with an abdominal MRI, followed by annual high quality renal ultrasound.

There is a 50% chance of a person who carries an FLCN mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early. However, as current genetic testing does not identify a mutation in all individuals who meets the clinical diagnosis of Birt Hogg Dubé syndrome, their first degree relatives (parents, siblings and children) should have at least baseline screening from age 20.

There’s lots that can be done to reduce risk. For more information, see the links below

• The US Genetics Home Reference site has information on the condition, how it is inherited as well as management advice.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with Birt Hogg Dubé syndrome. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• BHD Foundation is a support group for individuals and families affected by Birt Hogg Dubé syndrome. It is based in the USA but has members worldwide.
  We haven’t found a specific Australian Support Group for this syndrome yet. If you know of one, please tell us!
• Rare Cancers Australia is a support group for individuals and families affected by rare cancers.

Tumours rather than cancers per se. Not discussed in detail at this time.

The PTEN Hamartoma Tumour syndromes are caused by a mutation in the PTEN gene.
The syndromes include the following and the signs and symptoms vary greatly from individual to individual, even in the same family.

• Cowden syndrome (discussed below)
• Bannayan-Riley-Ruvalcaba syndrome (associated with a large head (macrocephaly), hamartomatous polyps in the intestine, lipomas and freckles on the penis)
• Proteus and Proteus-like syndromes (“overgrowth” syndromes, usually diagnosed in childhood).

Cowden syndrome is a heritable cancer syndrome that affects 1:200,000 people.

It is associated with the development of certain benign (non-cancerous) growths such as hamartomas as well as an increased risk of some cancers.  The breast, thyroid gland, uterus, bowel and skin are the most commonly affected organs.

Characteristic skin lesions develop over time and are present in almost all people with Cowden syndrome by the late 20’s. These lesions include trichilemmomas, papillomatous papules, acral keratosis and lipomas. They are not cancerous and usually require no treatment.

Macrocephaly (head circumference 97th percentile) is common and, in some individuals, intellectual delay.

Benign growths are very common and occur in the breast (benign fibrocystic breast disease in 80%), the thyroid (mulitnodular goitre in 60%), uterus (fibroids in 40%) and bowel (hamartomatous polyps in 30%). The risk of cancer is increased: the risk of breast cancer is 25% over a lifetime, the risk of uterine cancer is 5 to 10% and the risk of thyroid cancer is also 5 to 10% over a lifetime.

There is a 50% chance of a person who carries a germline PTEN mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early.

There’s lots that can be done to reduce risk. For more information, see the links below

• The US Genetics Home Reference site has information on the condition, how it is inherited as well as management advice.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with Cowden syndrome. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• PTEN World and PTEN Foundation are support groups for individuals and families affected by PTEN related syndromes. They are based in the USA but have members worldwide.
  We haven’t found a specific Australian Support Group for this syndrome yet. If you know of one, please tell us!

Gastrointestinal stromal tumours (GIST) are abnormal growths (tumours) that arise in the supporting tissue (stroma). GIST occur mainly in the stomach and small intestine but can occur anywhere in the gastrointestinal tract.

GIST are rare tumours affecting less than 1: 20,0000 people each year and familial GIST is even more rare, affecting less than 100 families world wide.

Familial GIST can be caused by germline mutations in the KIT and PDGFRA genes. When GISTs occur along with paragangliomas, a germline mutation in one of the SDH family of genes may be the cause (this is referred to as the Carney-Stratakis dyad)

Perhaps surprisingly, familial GISTs are more likely to be slow growing and less like to spread to other parts of the body (metastasise).

There is a 50% chance of a person who carries a germline KIT, PDGFRA or SDH mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for blood relatives. This allows screening of at risk relatives to start early.

For more information, see the links below

• The US Genetics Home Reference site has information on familial GIST.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with inherited cancer syndromes. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• These support groups are for individuals and families affected by GIST. They are based overseas but have members worldwide.The Life Raft group, GIST Support International and GIST Support UK.
  We haven’t found a specific Australian Support Group for this syndrome yet. If you know of one, please tell us!

In Australia, melanoma is the 3rd most common cancer. It affects 1:18 people, mainly over age 60.

When 2 or more first degree relatives (close relatives such as your parents, brothers and sisters or children) have had a melanoma, it is referred to as Familial Malignant Melanoma syndrome.

Increased risk of melanoma can be caused by genes that affect how someone looks (their “phenotype”) and how their skin reacts to sun exposure. These features include fair or red hair; pale skin; blue or green eyes, naevi (“moles”).

There’s lots that can be done to reduce melanoma risk. The most important is to avoid excess sun exposure. High risk families or people who have already had a melanoma should have annual skin checks with their doctor. These checks could include dermoscopy, total-body photography and/or sequential digital dermoscopy imaging.

In some families, the risk is also increased because of a mutation in a particularly gene, such as CDKN2A (other genes included CDK4, BAP1, POT1, ACD, TERF2IP and TERT).

These kind of inherited gene mutations are rare. For example, the average Australian diagnosed with a melanoma has only a 2% chance that it was caused by an inherited CDKN2A mutation. However, for someone who has had 3 or more melanomas and also has 2 or more close family members who have had a melanoma, the chance may be as high as 60%.

CDKN2A and CDK4 mutations increase melanoma risk and CDKN2A mutations has also been associated with an increased risk of pancreatic and kidney cancer risk, particularly if the individual smokes.

In some families, the melanomas may include melanomas of the eye (uveal melanomas). In this case, a mutation in BAP1 (the BRCA1–associated protein 1) may be considered, particularly if there is also a history of mesothelioma (a cancer of the lining of the chest cavity, usually associated with asbestos exposure). BAP1 related cancer syndrome is very, very rare and scientists are still learning about the lifetime cancer risks.

There is a 50% chance of a person who carries a germline BAP1 or CDKN2A mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early.

For more information, see the links below

• The US national Institute of health has this technical review of Familial Atypical Multiple Mole Melanoma Syndrome (associated with CDKN2A mutations)
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with inherited cancer syndromes. Currently there are so specific guidelines for hereditary melanoma syndromes. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• These support groups are for individuals and families affected by melanoma: The Melanoma Institute Australia and Melanoma Patients Australia

Around 2500 Australians are diagnosed with pancreatic cancer each year. When 2 or more closely related blood relatives (such as parent & child or brothers and/or sisters) are diagnosed the term Familial Pancreatic Cancer is used.

Is some families, an germline mutation in a key gene is responsible. These genes include STK11 (associated with Peutz-Jeghers syndrome) BRCA2 (associated with hereditary breast and ovarian cancer syndrome), PRSS1 or SPINK1 (associated with Hereditary Pancreatitis) and CDKN2A (associated with Familial Atypical Multiple Mole Melanoma syndrome)

The most effective way to reduce pancreatic cancer risk is not to smoke.

There is a 50% chance of a person who carries a germline STK11, BRCA2, PRSS1, SPINK1 or CDKN2A mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing may be available for blood relatives. This allows screening of at risk relatives to start early.

For more information on hereditary pancreatic cancer, see the specific syndromes or genes on our website or use the more general links below

• The Australian Pancreatic Cancer Genome Initiative has information about pancreatic cancer and their current research trials
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with inherited cancer syndromes. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu

Gorlin syndrome is also known as Nevoid basal-cell carcinoma syndrome (NBCCS). Other terms that have been used include multiple basal-cell carcinoma syndrome and Gorlin–Goltz syndrome.

Basal cell carcinoma’s are common, particular on sun damaged skin. Gorlin syndrome is caused by a germline mutation in the PTCH gene. It is rare, affecting around 1 in 30,000 people.

The signs and symptoms of Gorlin syndrome vary greatly from individual to individual, even in the same family. Most people with Gorlin syndrome develop multiple BCCs on their face, arms and upper body. Cysts in the jaw (keratocystic odontogenic tumors) are also common and appear before age 30. They can cause swelling and tooth displacement.

Some features don’t cause problems but are characteristic of Gorlin syndrome. Many individuals have punched out areas that appear on their palms or the soles of their feet, particularly after soaking in water. Almost all individuals over the age of 20 will have calcification of a membrane separating the hemispheres of the brain. This doesn’t cause problems but shows up on a skull Xray. Similarly, the bones of the ribs and/or the spine may have an unusual appearance. Having a large head (macrocephaly) is also common.

In less than 5% of children with Gorlin syndrome a rare brain tumour called a medulloblastoma (or primitive neuroectodermal tumor [PNET]) occurs.

Clinically, Gorlin syndrome is diagnosed when a combination of certain features are seen. (For more information see the links below)

There is a 50% chance of a person who carries a germline PTCH mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for blood relatives. This allows screening of at risk relatives to start early. This may include screening for Odontogenic keratocysts of the jaw in childhood and skin checks.

For more information, see the links below

• Genetics Home Reference site has information on the diagnosis of Gorlin syndrome
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with Gorlin sydnrome. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• These support groups are for individuals and families affected by Gorlin sydnrome. They are based in the USA but have members BCC Network or BCCNS Life Support Network

See Lynch syndrome and/or Familial Adenomatous Polyposis

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Hereditary Paraganglioma Pheochromocytoma syndrome is associated with mutations in the SDH family of genes (SHDA, SDHB, SDHC, SDHD and SDHAF2 ).

It is characterised by the development of paraganglioma and/or pheochromocytoma (“pheos” for short). In some cases, stomach cancers (called GISTs or GastroIntestinal Stromal Tumours) and/or kidney cancers occur. The likelihood of these tumours and cancers developing depends on which of the SDH genes is affected.

It is very rare, affecting 1 in a million people.

Paraganglioma and pheos can be associated with other syndromes including

• Von Hippel Lindau syndrome (VHL gene)
• Multiple Neuroendocrine syndrome (RET gene)
• Neurofibromatosis type 1 (NF1 gene)

Paraganglioma and pheos are very rare tumours. However, when they occur, there is a 10% to 30% chance that they occurred because of a germline (inheritable) gene mutation. Genetic testing is nearly always recommended. Often the clinical or family history and/or staining tests of the tumour gives a clue as to which gene may be involved. If not, a pheo gene panel test to check the 10 or more pheo genes may be recommended.

Paraganglioma arise from tissue that is part of the nervous system and that runs along the outside of the spine. This tissue is called the sympathetic and parasympathetic nervous system. Pheos are tumours found in the adrenal gland above the kidney. The tumours may grow and press on other structures. Sometimes they may become cancerous and spread.

Pheos and paraganglioma that arise in the sympathetic nervous system usually secrete hormones, especially if located in the chest, abdomen and pelvis. These hormones are involved in the “flight or fight response”. They are called catecholamines and include hormones such as adrenalin. The symptoms of intermittent catecholamine excess include episodes of heart palpitations associated with high blood pressure, facial flushing, headaches and sweating.

There is a 50% chance of a person who carries a germline SDH mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early. The SDHD gene is unusual: the mutation almost never causes problems if it is inherited from the mother (this is called imprinting).

There is lot’s that can be done to reduce risk. Individuals with an SDHB, SDHC or SDHD gene mutation should start screening from ages 5 to 10, depending on the mutation type. (The SDHA gene mutations are less likely to cause problems). This allows early detection and treatment of tumours. Screening includes annual blood pressure measurements and fasting blood tests as well as imaging of the spine, kidneys and adrenals every 2 to 3 years.

The SDH genes are involved in pathways that are switched on when oxygen levels are low. People with SDH and other paraganglioma and pheo gene mutations should not smoke or live at high altitudes.

For more information, see the links below:

• Genetics Home Reference site has information on Hereditary Paraganglioma Pheochromocytoma syndrome
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with Hereditary Paraganglioma Pheochromocytoma syndrome. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• The Pheo Para Trooperssupport group is for individuals and families affected by Hereditary Paraganglioma Pheochromocytoma syndrome, Paraganglioma and/or Pheochromocytoma. They are based in the USA but have members around the world.

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Tumours (growths) rather than cancers per se. Not discussed in detail at this time

Peutz-Jeghers syndrome is a rare, affecting 1 in 25,000 to 1 in 300,000 people.

Peutz Jeghers syndrome is caused by a mutation in the STK11 gene. A mutation is detected in more than 90% of people who meet the clinical diagnosis.

An individual must have one of the following to meet the clinical diagnosis:

• 2 or more histologically confirmed hamartomatous polyps of the Peutz Jeghers syndrome type
• a family history of Peutz Jeghers syndrome and either a hamartomatous polyp or mucocutaneous pigmentation
• any number of Peutz Jeghers syndrome hamartomatous polyps AND mucocutaneous pigmentation

Individuals with an STK11 mutation develop hamartomatous polyps. These are non cancerous growths that occur mainly in the small intestines, large intestines and the stomach. These polyps may first occur in childhood. They can cause bleeding and, as they can grow large, can cause abdominal pain and recurrent bowel obstructions and/or intussusceptions.

Most people an STK11 mutation and Peutz Jeghers syndrome have freckling (actually dark blue to dark brown macules referred to as mucocutaneous pigmentation) on the lips and inside the mouth. While freckles are very common, it is very unusual to have many on the lips or inside the mouth. These dark macules appear in childhood but may fade as a person gets older. They also occur around the mouth, lips and nostrils.

STK11 mutations increase the risk of cancer, particularly of the large and small intestine, stomach, pancreas, breast and ovary. Women may develop a very rare form of cervical cancer (that is not associated with the HPV virus) and men can develop a rare tumour of the testes called large calcifying Sertoli cell tumours, which secrete oestrogen.

More than one third of people with Peutz Jeghers syndrome have no family history of polyps or mucocutaneous pigmentation.

There is a 50% chance of a person who carries a STK11 mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives.

There’s lots that can be done to reduce risk. Screening for gastrointestinal tumours should start at age 10 and for women, breast screening should start at age 30.

For more information, see the links below

• The US Genetics Home Reference site has information on the condition, how it is inherited as well as management advice.
• The Cancer Institute’s eviQ pages provide accurate management and testing guidelines for individuals with STK11 mutations. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
• The Peutz-Jeghers Syndrome Online Support Group is a support group for individuals and families affected by Peutz-Jeghers syndrome. It is based in the USA but has members worldwide.

Paediatric diagnosis. Tumours (growths) rather than cancers per se. Not discussed in detail at this time)

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Paediatric diagnosis. Cancer risk increase with UV/radiation exposure. Not discussed in detail at this time.