Genetic Disorders and Predisposition Syndromes

What is a genetic disorder?

A genetic disorder happens when there is a change in a gene (mutation) that affects the way a cell grows and functions. This change is passed down through a person’s family (inherited).

While most childhood diseases are not thought to be inherited, some gene changes increase a person’s risk of developing cancer or another disease. These conditions are known as predisposition syndromes. This does not mean that a person will necessarily develop a disease, but they are at higher risk for doing so. The amount of that risk depends on the kind of genetic changes and other factors.

Some types of genetic disorders and predisposition syndromes include:

Ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is a rare genetic condition that affects the nervous system, immune system, and other body systems. Children with this condition have trouble coordinating their movements (ataxia) and develop problems with walking, balance, and using their hands. They may experience problems with their nervous system, which causes things like:

• Slurred speech
• Trouble moving their eyes from side to side
• Jerking movements they cannot control
• Muscle twitches
• Problems with how the nerves function, called neuropathy

People with AT have about a 40% risk of developing cancer, usually leukemia and lymphoma. They are very sensitive to radiation exposure, including medical x-rays.

Learn more about ataxia-telangiectasia.

Beckwith-Wiedemann spectrum or isolated lateralized overgrowth

Beckwith-Wiedemann spectrum (BWS) is a genetic disorder that may cause body parts to grow too much (hypertrophy). This overgrowth may happen in 1 area of the body, like the head or legs, or in several parts of the body. If it happens in only 1 part of the body, it is called lateralized overgrowth. If a person has lateralized overgrowth but shows no other signs of BWS, this is called isolated lateralized overgrowth or isolated hemihypertrophy.

Children with BWS or isolated lateralized overgrowth may grow into healthy adults. But they have an increased risk of developing cancers, like a type of kidney cancer called Wilms tumor and a liver cancer called hepatoblastoma. If tumors develop, it tends to be in childhood. By the time patients reach their teen years, their growth is more typical, and their cancer risk falls to that of the general population. Adults with BWS usually have a normal lifespan.

Read more about Beckwith-Wiedemann spectrum or isolated lateralized overgrowth.

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease is a group of genetic disorders that affect how a person’s nerves function. The nerves or the protective coating around them (myelin) become damaged due to incorrect gene function. CMT is a type of hereditary neuropathy. That is a nerve problem that can cause pain, numbness, tingling or weakness in different parts of the body. The problem is passed from parents to children.

CMT disease affects nerves that connect the brain to the rest of the body. These nerves are called peripheral nerves. Peripheral nerves include the motor nerves, which move the muscles, and sensory nerves that help a person feel heat, cold, and vibrations.

Learn more about Charcot-Marie-Tooth disease.

Carney complex

Carney complex is a disorder that causes a higher risk of several types of tumors, including noncancerous (benign) tumors in the heart known as cardiac myxomas.

Myxomas may appear on the skin and internal organs. People with Carney complex may also develop cancers of endocrine (hormone-producing) system, such as adrenal glands, thyroid, testes, ovaries, and pituitary gland. People with Carney complex usually have changes in skin coloring (pigmentation). Signs and symptoms of this condition often begin in the teens or early adulthood.

Learn more about Carney complex.

Constitutional mismatch repair deficiency syndrome

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare condition that increases a person’s risk of developing:

• Brain tumors
• Leukemia and lymphoma 
  
• Abnormal growths (polyps) in the intestines
• Cancers in the gastrointestinal tract
• Cancers in the female reproductive organs, including the uterus and ovaries
• Café au lait spots (flat brown spots on the skin)
• Patches of skin that are lighter than the overall skin color
• Other rare childhood cancers

A child with CMMRD can develop more than 1 type of cancer at a time, or more than 1cancer during their lifetime.

Read more about constitutional mismatch repair deficiency syndrome.

Diamond blackfan anemia

Diamond-Blackfan anemia (DBA) is a rare genetic blood disorder. If a person has this disorder, their bone marrow does not make enough red blood cells.

There may be no symptoms, mild symptoms, or severe symptoms. People with DBA may have physical symptoms such as pale skin, specific facial features, low birth weight, and delayed growth, among other issues. While they can live long lives with the proper treatment, some patients may have a greater risk of certain cancers later in life, such as:

• Colorectal cancer, a cancer of the colon and/or rectum
• Osteosarcoma, a cancer of the bone
• Myelodysplastic syndromes (MDS), a disorder where specific bone marrow cells do not work well. MDS may become leukemia.
• Acute myeloid leukemia (AML), a cancer of the bone marrow

Learn more about Diamond blackfan anemia.

DICER1 syndrome

DICER1 syndrome is an inherited disorder that increases a person’s risk for cancerous and noncancerous (benign) tumors. Tumors in the lungs, kidneys, ovaries, thyroid, and brain are the most common.

Affected people can develop one or more types of tumors. Members of the same family can have different types of tumors.

Learn more about DICER1 syndrome.

Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder that makes the muscles break down and get weaker over time. This disorder affects mostly males, causing muscle damage, breakdown, and weakness. Boys with DMD have a shorter lifespan than normal. Females may inherit it also, but their symptoms are less severe.

Read more about Duchenne muscular dystrophy.

Familial adenomatous polyposis 

Familial adenomatous polyposis (FAP) is a condition that mostly affects the digestive system. People with FAP often develop abnormal tissue growths called polyps in the large and small intestines. Some polyps can become cancerous if they are not removed.

People with FAP are at high risk of developing colon cancer and other digestive system cancers at a young age. They also have an increased risk of developing other tumors, cancers, or physical issues.

Learn more about familial adenomatous polyposis.

Friedreich’s ataxia

Friedreich’s ataxia (FA) is a rare, inherited disease that causes a slow, steady loss of muscle coordination and balance (ataxia). It can also cause speech problems, weakness, and a loss of feeling (hot, cold). It may affect heart function, cause scoliosis, and may make a person more prone to diabetes.

FA damages the nervous system, including nerves in the spinal cord and part of the brain (cerebellum).

Learn more about Friedreich’s ataxia.

Hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder where the body’s immune system does not work as it should. In HLH, certain kinds of white blood cells do not fight off infection as they should. So, people with HLH have a hard time fighting infections. Their immune system can be overly activated, damaging parts of the body such as the liver, spleen, bone marrow, or brain. Patients with this condition may have frequent high fevers, enlarged organs or lymph nodes, rashes, and other symptoms from too much inflammation.

Find out more about hemophagocytic lymphohistiocytosis.

Hereditary leiomyomatosis and renal cell carcinoma

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic condition that increases a person’s risk of developing kidney and skin tumors. The tumors may be cancerous (malignant) or not cancerous (benign).

Although symptoms vary, people with this condition may develop benign bumps on their skin. Women may develop growths (fibroid tumors) in their uterus. Patients with HLRCC have a greater lifetime risk of developing kidney cancer. They may also develop nerve cell tumors and tumors in the adrenal glands of the body, known as pheochromocytomas.

Learn more about hereditary leiomyomatosis and renal cell carcinoma.

Hereditary multiple osteochondromas

People with hereditary multiple osteochondromas have a rare condition that makes them more likely to develop 1 or more bone tumors, known as osteochondromas. The tumors may be benign (non-cancerous) or malignant (cancerous). The benign tumors may become cancerous over time. Patients with this condition may also have problems with growth, their joints, nerves, and discomfort when walking.

See more information about hereditary multiple osteochondromas.

Hereditary neuroblastoma

Neuroblastoma is a cancer of the nerve cells. A small number of children with neuroblastoma inherited the disease from a parent. Children with hereditary neuroblastoma are more likely to have a higher number of tumors and to be diagnosed earlier than children who have no family history of the disease.

People with hereditary neuroblastoma have a greater risk of developing:

• Neuroblastoma
• Ganglioneuroblastoma
• Ganglioneuroma

Learn more about hereditary neuroblastoma.

Hereditary paraganglioma-pheochromocytoma syndrome

Hereditary paraganglioma-pheochromocytoma syndrome is a condition in which tumors form in the peripheral nervous system (nerves in the head, neck, and body).

The tumors develop in bundles of nerves called paraganglia. Tumors that develop here are called paragangliomas. Another type of paraganglioma can form in the adrenal glands on top of the kidneys. These are called pheochromocytomas.

The symptoms vary depending on where the tumor is located and the tumor’s size.

As the person ages, their risk for developing tumors increases. The tumors are usually not cancerous, but they can become cancerous and spread to other parts of the body (metastasize). They may also develop tumors in their digestive tract, kidneys, and thyroid gland.

Read more about hereditary paraganglioma-pheochromocytoma syndrome.

Hereditary retinoblastoma

Retinoblastoma is an eye cancer that is often found in young children before the age of 5. The cancer develops in the part of the eye called the retina, which helps a person see color and light.

Retinoblastoma can be passed down through families (hereditary) or not passed down in families (sporadic). Hereditary retinoblastoma usually affects both eyes, but it may only develop in 1 eye. People with hereditary retinoblastoma also have an increased risk for tumors in other parts of the body, including the skin, bone, soft tissue, and brain.

Learn more about hereditary retinoblastoma.

Juvenile polyposis syndrome

Juvenile polyposis syndrome (JPS) is a genetic disorder that causes people to have a high risk of developing non-cancerous growths (called polyps) in the gastrointestinal tract (GI).

Polyps may form in the stomach, small intestine, and rectum. They are often found in the colon. “Juvenile” refers to the type of polyp seen in this condition. If the polyps are not removed, they may become malignant (cancerous). People with this syndrome have an increased risk of developing cancer of the stomach, small intestine, and pancreas during their lifetimes.

Read more about juvenile polyposis syndrome.

Li-Fraumeni syndrome

Li-Fraumeni syndrome (LFS) is a rare condition that increases a person’s risk for developing 1 or more cancers during their lifetime. It is usually inherited from a family member. Those with LFS may get cancer in their:

• Brain
• Breasts
• Bones
• Blood
• Adrenal gland (a tiny gland located on top of each kidney)
• Muscles
• Connective tissues that support and give shape to the body, like fat or cartilage

Less common, they may develop cancers in other parts of the body such as the:

• Skin
• Thyroid gland
• Lungs
• Esophagus, stomach, pancreas, or colon (digestive system)
• Kidney or bladder (urinary system)
• Uterus, ovaries, prostate, or testicles (reproductive system

See more about Li-Fraumeni syndrome.

Multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is a genetic disorder that increases the risk of developing tumors during a person’s lifetime. Most of these tumors are non-cancerous (benign), but they can sometimes be cancerous (malignant).

Most of the tumors develop in the endocrine system. People with MEN1 may also have tumors in other parts of their bodies.

Find out more about multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 2

Multiple endocrine neoplasia type 2 (MEN2) is a genetic condition that increases the risk of developing cancer in the endocrine system. The symptoms vary, depending on where the tumor is located. People with MEN2 have an increased risk of developing medullary thyroid cancer and pheochromocytomas, which are tumors of the adrenal gland. People with this condition may also develop other types of abnormal growths in endocrine tissues or glands.

Read more about multiple endocrine neoplasia type 2.

Neurofibromatosis type 1

Neurofibromatosis type 1(NF1) is an inherited disorder that can affect many areas of the body. These areas include the skin, eyes, bones, blood vessels, brain, and the nervous system.

People with NF1 also have a higher risk of developing certain kinds of cancerous and non-cancerous tumors. These conditions include neurofibromas, central nervous system tumors, breast cancer, pheochromocytomas, leukemias, and gastrointestinal stromal tumors (GIST). They may have other issues like café au lait spots (smooth, dark, flat birthmarks), freckles, benign growths in the eye, curved spine, larger than normal head, high blood pressure, and heart issues. The condition’s severity and body areas affected varies from person to person.

Learn more about neurofibromatosis type 1.

Neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is a genetic condition that mainly affects the nervous system. People with NF2 are at increased risk of developing tumors in their nerves.

The most common type of tumor in people with NF2 is vestibular schwannoma (also known as acoustic neuroma). In patients with NF2, vestibular schwannomas usually develop on both auditory nerves at an average age of 18-24. Almost all patients with NF2 will develop these by age 30. They may also have other nervous system tumors, such as:

• Meningiomas on the membranes around the brain and spinal cord
• Ependymomas in the cells of the brain or spinal cord that normally make fluid
• Astrocytomas in the supportive tissue of the brain or spinal cord
• Retinal hamartomas in the back of the eye

Find out more about neurofibromatosis type 2.

Nevoid basal cell carcinoma syndrome 

Nevoid basal cell carcinoma syndrome (NBCCS) is a condition in which people have a higher risk of developing certain kinds of cancerous (malignant) and non-cancerous (benign) tumors. The most common kind of cancerous tumors are medulloblastoma and basal cell carcinoma (skin cancer).

Tumors may develop in the skin, jaw, heart, ovaries, and brain. People with NBCCS may also have physical differences such as large head size caused by too much fluid in the brain, tiny white bumps on the face, extra fingers and toes, cleft lip and palate, and mental and learning challenges.

Learn more about nevoid basal cell carcinoma.

Noonan syndrome

People with Noonan syndrome are at a slightly increased risk of developing some types of cancers and blood disorders. These conditions include myeloproliferative disorder, juvenile myelomonocytic leukemia, neuroblastoma, and embryonal rhabdomyosarcoma. People with Noonan syndrome are also at a slightly increased risk of developing certain noncancerous tumors such as giant cell lesions and granual cell tumors. 

Learn more about Noonan syndrome.

PTEN Hamartoma Tumor Syndrome

People with the genetic condition called PTEN hamartoma tumor syndrome have non-cancerous growths, called hamartomas, in different parts of their bodies. People with PTEN hamartoma tumor syndrome are at higher risk of developing cancers of the:

• Breast
• Thyroid
• Kidney
• Uterus
• Colon
• Rectum
• Skin

Those with this syndrome usually do not develop cancer until adulthood. But some can can develop thyroid cancer. They may have features like larger-than-average head size, skin growth, non-cancerous growths (polyps) in their digestive system, non-cancerous growths in their thyroid gland, breast, and uterus (females), non-cancerous fatty cells under the skin (lipomas), weak muscles, and curved spine.

Learn more about PTEN hamartoma tumor syndrome.

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is a genetic condition that increases a person’s risk of developing certain types of cancer, including cancers of the:

• Digestive system
• Lung
• Breast
• Uterus
• Cervix
• Ovaries and testicles

People with PJS also have a higher risk of developing non-cancerous growths called polyps in the digestive system. Cancerous and non-cancerous growths may also appear in the kidneys, lungs, gallbladder, nasal passages, bladder, or ureters. People with PJS often also have small, dark-colored spots that look like freckles on some parts of their skin.

Learn more about Peutz-Jeghers syndrome.

Rhabdoid tumor predisposition syndrome

People with rhabdoid tumor predisposition syndrome have an increased risk of developing a rhabdoid tumor. These fast-growing tumors often occur in the brain, spinal cord, and kidneys.

Cancers may also develop in the soft tissues, lungs, skin, and heart. These tumors are most common in children. People with this syndrome have a higher risk of developing non-cancerous tumors that grow in the nerves, called schwannomas. These tumors are more common in adults. Some people never develop tumors.

Read more about rhabdoid tumor predisposition syndrome.

Spinal muscular atrophy

Spinal muscular atrophy (SMA) is a genetic condition that causes muscle weakness that gets worse over time. This is due to a loss of nerve cells called motor neurons, located in the brain and spinal cord.

SMA affects the muscles that help a person speak, breathe, and swallow. It also affects muscles that help perform daily activities, such as walking. When the nerve cells die, these muscles do not get signals from the nerve cells, so they begin to waste away. This is called muscle atrophy. This disease is more common in infants and children.

Find out more about spinal muscular atrophy.

Tuberous sclerosis complex

Tuberous sclerosis complex is a genetic disorder that may cause noncancerous tumors to occur in the skin, brain, kidneys, and other organs. Sometimes these tumors lead to serious health problems. Tuberous sclerosis complex also causes problems with a person’s development.

The signs and symptoms of the condition may be different in each person. Most people with this disorder have skin abnormalities, including light-colored skin patches, areas of the skin that are thicker or raised, and growths under the nails. In childhood, people with this condition may have tumors on their face, called facial angiofibromas.

See more about tuberous sclerosis syndrome.

Von Hippel-Lindau syndrome

Von Hippel-Lindau syndrome (VHL) is a rare condition that makes a person more likely to develop certain kinds of tumors. These tumors may be non-cancerous (benign) or cancerous (malignant).

People with VHL may develop central nervous system (brain and spinal cord) and retina tumors called hemangioblastomas. They may also have tumors of the inner ear called endolymphatic sac tumors. Other types of tumors include kidney cysts or cancer, pancreatic cysts or cancer, adrenal gland tumors known as pheochromocytomas, and genital tract tumors called papillary cystadenomas.

Read more about Von Hippel-Lindau syndrome.

WT1-related syndromes

WT1-related yndromes are conditions that increase the risk of having kidney cancer. People with these conditions have a greater risk of developing a cancerous tumor of the kidney known as Wilms tumor in the first 3 to 5 years of life. People with WT1-related syndromes may have other medical issues. These may include problems with the reproductive organs, genitals, eyes, and sometimes with behavior or development.

Find out more about WT1-related syndromes.

X-linked lymphoproliferative syndrome

X-linked lymphoproliferative syndrome (XLP) is a rare disorder of the immune system that usually affects only males. People with this have an abnormal immune response to infection with a common virus, Epstein-Barr virus (EBV). They develop a condition called fulminant infectious mononucleosis (FIM). They have too many immune cells that are active against the virus infection. These activated immune cells can build up in parts of the body like the liver, spleen, bone marrow, and brain. This reaction is called hemophagocytic lymphohistiocytosis (HLH).

If not treated, HLH can damage organs and even lead to death. There are 2 types of XLP: XLP-1 and XLP-2. Those with XLP-1 have a greater risk of developing lymphoma in their lifetime. Those with both types may also develop other problems with their immune response, not make enough blood cells (aplastic anemia), and experience abnormal swelling.

Learn more about x-linked lymphoproliferative syndrome.

Xeroderma pigmentosum

Xeroderma pigmentosum (XP) is an inherited condition that makes people too sensitive to ultraviolet (UV) rays from sunlight and some types of lighting. This condition mostly affects the eyes and areas of skin exposed to the sun. People with this condition may also have problems with their nervous system.

People with XP have a high risk of developing skin cancer and must wear sun protection. Without sun protection, about half of children with this condition develop their first skin cancer in early childhood. People with XP often develop multiple skin cancers during their lifetime. They can get cancer on their face, lips, eyelids, scalp, in their eyes, and the tip of their tongue. People with XP may also have an increased risk of other types of cancer such as brain tumors, blood cancers, and thyroid cancers. If people with XP smoke, they have a higher risk of developing lung cancer.

Read more about xeroderma pigmentosum.

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