Genetic Syndromes

author/s: Dr M. Teresa Solé Pujol


What syndromes are associated with colorectal cancer?

A syndrome refers to an entire set of malformation or abnormalities that are observed in an individual and that affect different structures or organs of the body, all originated by a common cause.

A syndrome associated with colorectal cancer is the set of malformations or abnormalities that share the same aetiology and that can affect different structures of our body, among these the colon and the rectum.


What should I do done when a syndrome that can present with colorectal cancer is diagnosed?

You should see a geneticist to assess the syndrome and, once diagnosis is established, the geneticist will give you genetic counselling.


What is genetic counselling?

A session in which the affected individual (s) discusses with the geneticist physician the study, diagnosis, prognosis and prevention of the syndrome and future complications.

Prevention can be carried out prenatally (before the individual is born) or postnatally, after birth, to prevent future complications of the disease.

During the session, the familial past history will be assessed to determine whether it is necessary to study other members of the family, as there may be others affected or likely to be affected.To do this, a genealogic tree is drawn using international symbols. (see flash animation)

Lastly, the geneticist, in base of the existing problem, will indicate which doctors need to be looking after the case, as genetics is an area that deals across all medical specialties and each case is different.


Why is colon cancer hereditary in some families?

Because one of the progenitors has the mutated gene that is transmitted to the offspring. 


How is it transmitted?

Through the ovum (female) or the spermatozoon (male) at the time of fertilisation.

Remember that males have 46 chromosomes, grouped into 23 pairs, and that chromosomes are like our cookbook recipes….. let´s make a heart …. a kidney ready…….. etc.

From time to time, the recipes are wrong and the organs or tissues that come out based on their information are also wrong. The failure can become apparent during the prenatal period (before birth) or later on in life during the postnatal period (after birth).


And, what types of inherited syndromes are there?

It depends on each syndrome, but many of the genes involved in colorectal cancer have an autosomal dominant heredity.


And, what does this mean?

Very easy, “welcome to the fascinating Genetics world”. We have inherited all our traits from our ancestors, our hair colour, the shape of our nails…… ,through the DNA at the time of fertilisation. Sometimes part of the information that contains the DNA is damaged and this can lead to different types of problems.

You will ask yourself “Can I pass down my disease onto my children?” and the answer is in many cases YES, you can.

You will ask yourself: “How can I prevent it”? and the answer is “IT DEPENDS” on whether you have already had children or they still have to be born:

    • If the children are already born, we cannot prevent the transmission. What we can do is to study them to find out if they have inherited the condition. If this is the case, we can help them by offering medical assessments and regular follow up to control the condition, deciding the best therapeutic option as we go along.

    • If the children have not been born yet, we can resort to prenatal diagnosis or to assisted reproduction techniques such as ovocyte or sperm donation, depending on the gender of the affected progenitor. We can also resort to preimplantational diagnosis.

You will ask yourself “And, what does all of this consist of? Why do diseases develop? Why us?” and the answer is simple. Visit: Genetics Made Easy,  (non profit, educative web for general population).

We recommend that you read the entire page from the beginning to the end. You will see that it has been written using very clear and simple words. You can also enjoy lots of static illustrative drawings and flash animations.

This web site will help you learn more about diseases and their risks; how they are diagnosed and fight with current techniques…. Prenatal diagnosis, assisted reproduction techniques: in vitro fertilisation, preimplantational diagnosis, gamete donation (ovum and spermatozoon), or how it will be done in the future…. regenerative medicine with stem cells and gene therapy.

This site will provide you with links that you will find most useful, to acquire general knowledge and referrals.


What are the most frequent syndromes associated with colorectal cancer?

These are the most frequent syndromes. Click on any of them to obtain further information:

    1. Familial adenomatous polyposis.

    2. Hereditary colorectal cancer with no polyposis.

    3. Juvenile polyposis.

    4. Mixed polyposis.

    5. Peutz-Jegher´s syndrome.


Familiar adenomatous polyposis (FAP)

Incidence: 1 in 6,000-13,000

Penetrance: Nearly 100% (classical form) .

Heredity: Autosomal dominant.

Gene involved in this type of cancer: APC located in chromosome 5q21

Risk to develop the cancer: 100%

Clinical findings

Of all the cases of colorectal cancer, 1% are caused by familial adenomatous polyposis (FAP). Affected individuals develop colorectal cancer around the age of 40, unless they have priorly undergone a colectomy (surgical removal of the colon and rectum).

Other risks include cancer of Vater´s ampolla (junction point between the biliary duct and the small intestine) of the biliary ducts, thyroid, small intestine, thyroid (non medullary type cancer) or hepatoblastomas in the infancy.

Diagnostic criteria

Presence of over 100 colorectal polyps (the majority of individuals already present the polyps at the age of 20). Molecular biology studies must be performed to detect the mutation or wrong recipe.

Cancer control

Individuals afflicted with FAP are instructed to undergo sigmodoscopies or colonoscopies every year after the age of 10-12, followed by a total colectomy when the polyps start to appear.

Clinical variants of familial adenomatous polyposis


In this variant of FAP, the affected individuals have a smaller number of colorectal polyps and they appear later in life. They can also have polyps of the upper gastrointestinal tract.


This variant is caused by mutation in the MYH gene and follows an autosomal recessive pattern. The number of polyps is also inferior to the standard in FAP. This syndrome has been recently described and some characteristics are still to be defined.


In this variant of FAP, the individuals can also present sebaceous cysts, lipomas, desmoid tumours, fibromas, osteomas of the jaw, epidermoid cysts, teeth that have not come out, and hypertrophy of the pigmentary epithelium of the retina (eye): It has a very low frequency.


In this variant of FAP, individuals can also present brain tumours, particularly medublastoma, and also are at increased risk of developing cancer of the stomach and basal cell carcinoma. It has a very low frequency.


In this variant of FAP, the affected individuals develop multiple desmoid tumours but not colorectal polyposis. It has a very low frequency.

Diagnostic criteria of the clinical variants of familial adenomatous polyposis:

The same as for FAP, but adding specific tests according to the type of tumour or pathology that we want to rule out in each case, for instance: diagnostic imaging studies (X-rays, magnetic nuclear resonance, scanners), blood tests (tumoral markers, chromosomal studies, specific determinations), invasive procedures (endoscopies, colonoscopies), tissue biopsies, etc.


Hereditary colorectal cancer with no polyposis (HNPCC), or Lynch syndrome

Incidence: 1 into 200 to 1 in 1000.

Penetrance: Around 90%.

Heredity: Autosomal dominant.

Genes involved in this type of cancer:

MSH2 localised in chromosome 2p22

MLH1 localised in chromosome 3p21

PMS1 localised in chromosome 2q31

PMS2 localised in chromosome 7p22

MSH6 localised in chromosome 2p16

Risk to develop this cancer: 75%.

Clinical findings

Of all the cases of colorrectal cancer, nearly 2% are caused by this aetiology.

In the classical Lynch syndrome, these tumours are not accompanied by many polyps and, frequently, are localised in the right side. It is estimated that 30% of women who present this type of cancer can develop endometrial (uterine), ovarian, or breast cancer.

Increased risk for both men and women to develop cancer of the stomach, small intestine, urether and kidney, as well as other tumours at the level of the gastrointestinal and genitourinary tracts.

It has recently been described that at least half of families who meet the criteria for Lynch´s syndrome do not present the characteristics described in the classical syndrome and that the cancer is not due to alterations of the described genes. These families present the cancer at an older age, the cancer does not usually involve the right side of the colon and appear to have fewer extracolonic cancers. The genetic basis of this group are yet to be defined.

Diagnostic criteria

It is diagnosed based on the pattern and type of cancer that manifests in the family and on the basis of Amsterdam and Bethesda´s diagnostic criteria by means of molecular biology studies to identify the mutation or badly written recipes.

Cancer control

Individuals affected with HNPCC are recommended to undergo a colonoscopy every 1-2 years after the age of 25 years or 10 years before the age of the youngest affected relative when she or he was first diagnosed with colorectal cancer.

Clinical variants of hereditary non-polyposic cancer of the colon:


In this variant, affected individuals, apart from presenting all the pathology of HNPCC, can also present tumours of the sebaceous glands and keratoacantomas of the skin. This variant is very rare.


In this variant, individuals, apart from presenting all the pathology of HNPCC, also run the risk of developing brain tumours (gioblastomas). This variant is also very rare.

Diagnostic criteria of the clinical variants of hereditary non-polyposic cancer of the colon

The same as for HNPCC, but running specific tests depending on the type of tumour or pathology that we wish to rule out in each case, for instance, diagnostic imaging studies (X-rays, magnetic resonance, scanner), blood tests (tumoral markers, chromosomal studies, specific determinations), invasive procedures (endoscopy, colonoscopy), tissue biopsies, etc.


Juvenile polyposis

Incidente: Rare.

Penetrance: Around 90%.

Heredity: Autosomal dominant.


SMAD4 located in chromosome 18q21.1

BMPRIA located in chromosome 10q22-23

Risk to develop cancer:

Around 30%.

Clinical findings

Hamartomatous polyps in the colon, stomach and small intestine. Anaemia and bleeding due to the size and number of gastrointestinal polyps. The risk to suffer from cancer includes the colon, stomach, pancreas and small intestine. Some children can have associated abnormalities such as polydactilia, club feet, cardiac defects, small head circumference (often below the percentile 10) and mental retardation.

Cancer control

Frequent colonoscopies and endoscopies to rule out tumours in the upper gastrointestinal tract.


Hereditary mixed polyposis

Incidence: Rare.

Penetrance: It can be over 90%.

Heredity: Autosomal dominant.

Gene: HMPS located in chromosome 6q.

Risk to develop cancer: It can be over 90%.

Clinical findings

Individuals with this type of polyposis can develop multiple atypical polyps in the colon. Polyps of other histological types have also been described, including adenomatous or hyperplastic lesions. Individuals with this type of polyposis run an increased risk of developing colon cancer or rectal cancer.

Diagnostic criteria

Atypical juvenile polyposis of the colon. Molecular biology studies to identify the mutation or wrong recipe are not yet available.

Cancer control

Regular follow up of the polyps of the colon or rectum.


Peutz Jegher's syndrome

Incidence : 1 in 120,000.

Penetrance: Around 100%.

Heredity: Autosomal dominant.

Gene: STK 11 located in chromosome 19p 13.3

Risk to develop cancer: 50%.

Clinical findings

Multiple hamartomatous polyps along the entire gastrointestinal tract (more frequent in the thin intestine) and multiple pigmented spots in the lips and oral mucosa. The complications of polyps include anaemia and bleeding. Pigmented lesions of the skin do not usually cause medical problems. Individuals affected with this syndrome are at increased risk of developing colon cancer. Women also run a higher risk to develop breast, pancreas, uterine or ovarian cancer. Men can also develop cancer in the pancreas, lung and testicles.

Diagnostic criteria

Histopathological confirmation of gastrointestinal hamartomatous polyp (s) and to present two or more of the following:

-polyposis of the thin intestine.

-more than one relative with Peutz-Jeghers syndrome.

- pigmented maculae of the bucal mucosa, lips, fingers or toes.

Molecular biology studies should also be carried out to identify the mutation or wrong recipe.

Cancer control

Upper GI tract endoscopies and colonoscopies. Women should have mammographies, pelvis examinations, cytology, and abdominal and pelvic ultrasound. Men should undergo testicular examinations regularly.