Dyskeratosis Congenita

Dyskeratosis congenita (DC or DKC) is a rare genetic disorder that affects many different parts of your child’s body. The first signs usually appear on your child’s skin, nails and the inside of their mouth before age 10. DC can lead to complications like bone marrow failure or cancer in childhood, adolescence or adulthood. Bone marrow failure is the first sign of DC in some children.

DC is part of a spectrum of conditions called telomere biology disorders. Telomeres are the protective caps at the ends of your child’s chromosomes (structures that contain their DNA). Telomeres allow organs and tissues in your child’s body to develop normally and work as expected. With DC, your child’s telomeres are shorter than they should be. This can lead to a wide range of issues.

Other telomere biology disorders (sometimes called TBDs or telomeropathies) include:

• Hoyeraal Hreidarsson Syndrome (HH)
• Revesz syndrome (RS)
• Coats plus syndrome

What are the features of dyskeratosis congenita?

Children with “classic DC,” or the form researchers first recognized, have:

• Abnormal skin color. Skin on your child’s neck, upper chest and arms might appear to have a net-like or lacy pattern. The affected skin might be lighter or darker than your child’s normal skin tone.
• Malformed or missing nails. Your child’s fingernails and/or toenails may have ridges or cracks. They may peel away or grow slowly. In some cases, the nails may be smaller than normal or missing. These changes might affect just some nails, with others appearing normal.
• Leukoplakia. You may notice thick, white patches on your child’s tongue or the insides of their cheeks.

Experts call these features the “mucocutaneous triad.” “Muco” refers to the mucous lining of your child’s mouth, and “cutaneous” refers to their skin. But DC is a complex condition that affects every child a little differently.

For example, some children develop bone marrow failure before the “triad” features. In this case, providers do testing to uncover the cause of bone marrow failure, which may lead to a dyskeratosis congenita diagnosis.

Other children have a wide range of features that, on the surface, seem unrelated. But through exams and testing, providers sometimes recognize that DC is what causes all of them.

Other possible features of DC include:

• Bone problems, including osteoporosis, fractures and avascular necrosis of the hips and shoulders
• Cancers such as blood cancer (leukemia), skin cancer and head/neck squamous cell cancer
• Coordination and balance issues (ataxia)
• Decreased production of sex hormones (hypogonadism)
• Decreased immune function (immunodeficiency)
• Dental issues beyond what’s typical — like many cavities or extensive tooth loss
• Developmental delays or disabilities
• Esophageal narrowing. This can lead to regurgitation and problems with feeding or weight gain
• Excessive sweating
• Hair loss or early greying
• Liver disease
• Lung disease
• Short stature
• Small head size (microcephaly)
• Urethral narrowing
• Watery eyes and inflammation of the eyelids

What causes dyskeratosis congenita?

Genetic variations (changes from what’s expected, sometimes called mutations) cause dyskeratosis congenita. The specific genes affected are those that control the function of telomeres (protective caps on the ends of your child’s DNA).

When telomeres don’t work right, certain cells in your child’s body also can’t work normally. This leads to a shortage of blood cells, problems with organ function and other complications.

Is dyskeratosis congenita inherited?

Yes, dyskeratosis congenita can pass from one generation to the next. A child can inherit it from one or both of their biological parents. It’s also possible for dyskeratosis congenita to appear for the first time in a child without a family history of the condition.

Which genes are associated with dyskeratosis congenita?

Genes that researchers commonly link with dyskeratosis congenita and telomere biology disorders include:

• DKC1
• TERC
• TERT
• TINF2
• ACD
• CTC1
• DCLRE1B
• NHP2
• NOP10
• NPM1
• POT1
• RPA1
• STN1
• TCAB1
• PARN
• RTEL1

What are the complications of dyskeratosis congenita?

Dyskeratosis congenita can lead to a wide range of complications, including:

• Bone marrow failure (most common complication, typically before age 30)
• Pulmonary fibrosis
• Myelodysplastic syndrome (MDS)
• Acute myeloid leukemia (AML)
• Head and neck cancer
• Skin cancer
• Liver fibrosis

At what age is dyskeratosis congenita diagnosed?

Diagnosis usually happens in childhood or adolescence. That’s when the earliest signs of dyskeratosis congenita usually appear. But some people don’t notice signs or receive a diagnosis until they’re adults.

How do healthcare providers diagnose this condition?

Providers diagnose dyskeratosis congenita by:

• Talking to you about your child’s signs and symptoms
• Reviewing the medical history of your child and their biological family members
• Doing a physical exam
• Ordering tests

Providers look for known features of the disease (like skin changes, nail changes and white patches in your child’s mouth). They use test results to confirm or rule out DC as the cause of those features.

Tests for DKC

Your child’s provider may order many tests. Some directly help with diagnosis. Others uncover additional features of the disease that may affect your child’s health and treatment plan.

The main tests for diagnosing dyskeratosis congenita are:

• Flow cytometry, which measures how long your child’s telomeres are. Test results provide a telomere length and a percentile — the percentile shows how your child’s telomere length compares with that of their peers
• Genetic testing, which looks for gene variants associated with DKC

Providers usually draw a sample of blood for these tests. In unique situations, they take samples of other types of tissues (for example, they might perform a skin biopsy).

Additional tests

Other tests your child might need include:

• Dental exam
• Endoscopy
• Eye exams
• Skin exams
• Bone marrow exams
• Imaging tests to check various parts of the body, like their brain, heart, lungs, liver or bones
• Lung function tests
• Immune function tests
• Neuropsychological testing

How do providers treat dyskeratosis congenita?

Providers tailor treatment to your child’s needs. There’s no standard treatment plan because DC affects each child differently.

Possible treatments include:

• Blood transfusions to give your child healthy red blood cells and platelets
• Androgen therapy to support healthy blood cell counts and possibly lengthen your child’s telomeres (temporarily)
• Stem cell transplant to cure bone marrow failure, MDS or leukemia (but only in certain situations when the benefits outweigh the risks)

Your child’s providers will discuss available treatment options with you. Currently, treatments can’t cure DC or permanently change telomere length. Instead, treatment targets specific features or complications of the condition. Researchers are hard at work trying to find new treatments that may help children and adults with DC.

What providers will care for my child?

Providers from many different specialties will work together to plan treatment. Your child may have one “medical home,” or a provider who works most closely with you and coordinates care with other providers.

Your child’s care team may include general pediatricians as well as pediatric:

• Dentists
• Dermatologists
• Endocrinologists
• Gastroenterologists
• Hematologists/oncologists
• Immunologists
• Neurologists
• Ophthalmologists
• Otolaryngologists
• Pulmonologists
• Geneticists

Can dyskeratosis congenita be prevented?

There’s no known way to prevent this genetic condition. If you or a biological family member has DC, you may wish to speak with a genetic counselor. They can help you understand the chances of your children inheriting the condition.

What can I expect if my child has dyskeratosis congenita?

Your child’s outlook, or what you can expect going forward, is hard to predict. DC may limit your child’s lifespan. It’s difficult to say what their life expectancy might be.

Dyskeratosis congenita comes with many unknowns. Your child’s care team will give you as much information as possible. They’ll also explain how often your child needs exams and testing.

What is the most common cause of death in dyskeratosis congenita?

Bone marrow failure is the leading cause of death in people with dyskeratosis congenita. This is because the lack of healthy blood cells leads to serious infections and bleeding.

Other common causes of death include lung disease and cancer.

What can I do to care for my child?

Learning your child has dyskeratosis congenita might make you feel helpless. But there’s a lot you can do to support your child’s health and lower their risk of complications.

People with DC face an increased risk of certain cancers and lung disease. Environmental factors, like sun exposure and smoking, raise their risk even further. You can help your child by encouraging them to:

• Use sunscreen and protective gear (like hats and long sleeves) when outdoors
• Limit their time in strong sunlight
• Avoid all tobacco products
• Limit or avoid alcohol

Your child’s care team will give advice according to your child’s needs. They may also recommend advocacy or support groups. For example, there are many organizations that support people with rare diseases. Team Telomere is a group for people with DC and other telomere biology disorders.

When should I seek medical care for my child?

Your child will have many medical appointments. Their care team will tell you exactly which providers to see and how often.

These visits are very important. They help providers keep an eye on your child’s condition and adjust treatment. DC causes a wide range of complications that you can’t always notice at home. Testing can show issues like bone density loss or the early signs of cancer.

Providers may explain how to do self-checks at home for things like skin cancer or oral cancer. These don’t take the place of seeing a provider. But they’re an important way to catch certain signs early so your child can get care right away.

What questions should I ask my child’s care team?

Questions that may help you learn more after a dyskeratosis congenita diagnosis include:

• Which disease features does my child have?
• What complications are possible?
• What treatments do you recommend?
• What are the benefits and risks of these treatments?
• Can you recommend a support group or other resources?
• How can I explain this condition to my child?
• Do you recommend genetic testing for me or other biological relatives?

For older children and teens, it may help to ask:

• How can I help my child take charge of their own healthcare in ways appropriate to their age?
• How and when should we prepare to transition my child from pediatric to adult providers?

What are telomeres?

Telomeres are repeat sequences of DNA found at the ends of each of your child’s chromosomes. All your child’s genes are lined up in between them. Providers often compare telomeres to the plastic caps at the tips of shoelaces. These caps protect your shoelaces from damage. Similarly, telomeres protect your child’s genes.

Chromosomes are in virtually all the cells in your child’s body. And those cells are constantly making copies of themselves (replicating) to keep your child’s organs and tissues working normally.

Each time a cell replicates, its chromosomes get copied. And each time this happens, a chromosome’s telomeres get a little bit shorter. This is normal. An enzyme called telomerase jumps into action and builds the telomeres back up to a healthy length so the cell can keep replicating. If telomeres get too short, the cell stops replicating.

With dyskeratosis congenita, gene variants cause abnormal telomere shortening. This can happen in several ways. For example, a gene variant might interfere with telomerase production. Or it might keep telomerase from reaching the telomere. So, your child’s telomeres get shorter and can’t build back up again.

Once the telomeres inside a cell get too short, that cell stops making copies of itself. As more and more cells stop replicating, various organs and tissues in your child’s body don’t have what they need to work properly. This is how short telomeres lead to the signs, symptoms and complications of dyskeratosis congenita.

What is Zinsser-Cole-Engman syndrome?

Zinsser-Cole-Engman syndrome and dyskeratosis congenita are two different names for the same condition. In 1906, researchers who discovered this condition named it Zinsser-Cole-Engman syndrome. But today, most people refer to it as dyskeratosis congenita.