DNA repair disorders

Every cell in your body contains DNA. DNA is your hereditary material. You can think of it as an instruction manual for your body. Your DNA gets damaged every day. This is caused, for example, by sunlight, cigarette smoke, X-rays, certain medications (such as chemotherapy), or processes within your body. Usually, your body can repair this damage itself. With a DNA repair disorder, this does not work well. As a result, damage accumulates. Cells function less effectively or die off more quickly. This leads to premature aging. Sometimes cells become unstable. This increases the risk of cancer. There are many different DNA repair disorders. The symptoms vary depending on the disease.

DNA repair stoornissen zijn erfelijk. Je wordt ermee geboren. Ze ontstaan door aangeboren veranderingen (mutaties) in het DNA, je erfelijk materiaal. De mutaties zitten in genen (instructieboekjes) die belangrijk zijn voor het repareren van beschadigd DNA.

DNA repair disorders are inherited in an autosomal recessive manner. This means that you only develop the disease if you inherit a gene with a mutation from both parents. Someone who has only one defective gene is a carrier. Carriers have no symptoms. If both parents are carriers, they have an increased chance of having a child with a DNA repair disorder. That chance is 25% (1 in 4) for each child. This applies to both sons and daughters.

DNA repair disorders are very rare conditions. They are estimated to affect approximately 1 in 500,000-1,000,000 people.

Examples of DNA repair disorders that we see in our consultation hours:

• Cockayne Syndrome (CS)
• Trichothiodystrophy (TTD)
• Xeroderma Pigmentosum (XP)
• Bloom Syndrome (BS)
• Nijmegen Breakage Syndrome (NBS)
• Rothmund-Thomson syndrome (RTS)

Cockayne Syndrome (CS)

Children with CS have short stature, low weight, and a small head circumference. They often have difficulty eating. Development is delayed. Development may also regress at a later age. The skin and eyes are hypersensitive to sunlight. The face and body show signs of accelerated aging. Other common problems include:

• Hearing loss
• Eye problems
• Bone and dental abnormalities
• Liver and kidney abnormalities
• Nervous system problems, such as spasticity (stiffness) or impaired balance.

CS is incurable. The severity of the disease can vary. Click here for more information about CS.

Trichothiodystrophy (TTD)

Children with TTD have extremely brittle and fragile hair, brittle nails, and dry, scaly skin (ichthyosis). In about half of children with TTD, the skin and eyes are hypersensitive to sunlight. Development is delayed. Development may also regress later in life. Sometimes there are also behavioral problems, such as autism. Children with TTD show signs of accelerated aging. This is particularly visible in the face. Other common problems include:

• Growth and feeding problems
• Immune disorders (leading to increased illness)
• Hearing loss
• Eye problems
• Dental problems

TTD is incurable. Click here for more information about TTD.

Xeroderma Pigmentosum (XP)

In children and adults with XP, the skin and eyes are extremely hypersensitive to sunlight. Redness and blisters can develop with minimal sun exposure. Usually, many freckles appear at the age of 1-2 years. Over time, these develop into larger pigment spots.

People with XP have a very high risk of developing (malignant) skin tumors. Skin tumors often develop during early childhood. Eye infections and eyelid abnormalities are also common. The following problems occur in a portion of people with XP:

• Developmental delay
• Nervous system problems, such as spasticity (stiffness) or impaired balance
• Hearing loss

XP is incurable. The severity of the disease can vary. Click here for more information about XP.

Bloom syndrome

Children and adults with Bloom syndrome are short in stature and have a small head circumference. The skin is often (mildly) hypersensitive to sunlight. There is an increased risk of various forms of cancer from a young age. People with Bloom syndrome usually have normal development and intelligence. In some people with Bloom syndrome, the following problems occur:

• Immune disorders (leading to increased illness)
• Hormone disorders (such as diabetes or thyroid abnormalities)
• Difficulty eating (in childhood)

Bloom syndrome is incurable. Click here for more information about Bloom syndrome.

Nijmegen Breakage Syndrome (NBS)

Children with NBS are short in stature and have a small head circumference. Their immune system functions less effectively. As a result, they get sick more often. There is an increased risk of various forms of cancer from a young age. Lymphomas and leukemia, in particular, are common. Development usually proceeds normally at first. Later, learning difficulties may arise, sometimes leading to a (mild) intellectual disability. However, children and adults with Nijmegen Fracture Syndrome can also have normal intelligence.

Click here for more information about NBS.

Rothmund-Thomson syndrome (RTS)

In RTS, a typical skin rash (poikiloderma) develops in early childhood. This rash usually starts on the cheeks and spreads to the arms and/or legs. The rash persists throughout life. Children and adults with RTS have dental abnormalities (for example, too many or too few teeth) and little or thin hair. There is an increased risk of anemia and various forms of cancer. Other common problems include:

• Short stature
• Difficulty eating
• Skeletal abnormalities (for example, missing or malformed bones)
• Eye abnormalities (cataracts at a young age)

People with RTS syndrome usually have normal development and intelligence. RTS is incurable. Click here for more information about RTS.