What is Dyskeratosis Congenita?
Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare skin disorder first identified by Zinsser in 1906. It’s mainly characterized by three symptoms: white patches in the mouth (known as oral leukoplakia), malformed nails (nail dystrophy), and a particular pattern of skin darkening (reticular hyperpigmentation).
Most individuals suffering from this syndrome have a fault in their DKC1 gene. This gene is responsible for creating a protein known as dyskerin, which plays a key role in sustaining structures called telomeres in our cells.
This disorder is usually passed down in families via an x-linked recessive pattern, which means males are thrice as likely to be affected as females. However, the actual visible symptoms can differ significantly from person to person. Some people might experience thin, wrinkled skin, eye issues, or even bone marrow failure.
Treating this condition is challenging, and it often calls for a team of healthcare professionals to work together for the best possible care.
What Causes Dyskeratosis Congenita?
Dyskeratosis congenita, a disease that affects the skin and many other parts of the body, is caused by problems with how telomeres are preserved. Telomeres are portions at the ends of our chromosomes that keep these chromosomes from getting too short every time DNA is reproduced. Some genes linked to this disease work on maintaining these telomeres.
One particular gene, DKC1, creates a protein called dyskerin and is often problematic in people with this disease. Dyskerin helps stabilize an enzyme called telomerase. This enzyme is crucial to control the length of telomeres. If proteins like dyskerin are missing, the telomeres keep getting shorter, resulting in cell death or aging.
Furthermore, unstable telomeres can also lead to cancer, especially in cells that divide quickly. There are several genes, such as TINF2, TERC, TERT, C16orf57, NOLA2, NOLA3, WRAP53/TCAB1, and RTEL1, that can undergo mutations in dyskeratosis congenita.
Risk Factors and Frequency for Dyskeratosis Congenita
Men are more likely to be affected than women by a ratio of about 3 to 1. This corresponds with the fact that the most common way this trait is inherited is through an x-linked recessive pattern. Women who are carriers often experience milder symptoms, however, in some cases, they may also experience severe symptoms.
Signs and Symptoms of Dyskeratosis Congenita
Dyskeratosis congenita is a disorder that affects various parts of the body. Changes usually begin appearing in childhood and become more noticeable over time. Below are the common symptoms associated with this condition:
- Changes in fingernails and toenails (e.g., ridges, abnormal growth)
- Skin changes, including discolored patches on the face, upper body, and thighs
- Dry or excessively sweaty skin
- Discoloration, thinning and graying of hair
- Unhealthy conditions in the mouth like leukoplakia (white patches), blisters, erosions, and tooth decay
- Joint and bone problems like osteoporosis (brittle bones), avascular necrosis (loss of blood to bones), resulting in joint pain and disability
- Eyes can develop conditions like ectropion or entropion (eyelid turning out or in), leading to corneal abrasions (scratches on the eye surface)
- Gastrointestinal and urinary issues like stenosis (narrowing of the gut or urinary tract), cancer, or liver scarring
- Lung scarring
- Bone marrow failure, which leads to changes in blood counts and can progress to conditions like myelodysplastic syndrome (abnormal blood cells) or leukemia (blood cancer)
It’s important to note that people with dyskeratosis congenita may not experience all these symptoms, and the progression of the disorder can vary among individuals.
Testing for Dyskeratosis Congenita
Understanding and diagnosing conditions primarily involve a combination of patients’ medical history, physical check-ups, skin, mucous membrane, or bone marrow biopsies, as well as a procedure called flow-fluorescence in situ hybridization (FISH). By observing tissue samples from these biopsies under a microscope, doctors can identify disease-related changes and check for signs of potential cancer. A bone marrow biopsy can reveal flaws or leukemia changes in the production and development of blood cells.
Flow-fluorescence in situ hybridization is a lab technique used to identify and map genetic material in an individual’s cells. In this context, FISH can reveal telomere shortening (a sign of aging) in disease-fighting white blood cells. Furthermore, genetic testing may find any associated genetic abnormalities previously identified in similar cases.
Treatment Options for Dyskeratosis Congenita
Treating this condition often needs a team of medical professionals and regular check-ups for any related complications. To monitor and protect against skin cancer, it is recommended that patients undergo a yearly skin screening and always protect their skin from the sun. Dental check-ups twice a year are also advised to scan for oral cancer. Depending on the patient’s symptoms, they might also need to see an ear, nose, throat specialist annually for skin cancer screening.
It could also be beneficial for a gastroenterologist to perform regular endoscopies of the esophagus and/or colon. These screenings check for any tightening (strictures) or potential cancer. Regular blood tests and bone marrow exams are carried out to check for changes in bone marrow or signs of cancer. It’s also important to have lung health assessments regularly to look for signs of lung scarring (fibrosis).
Patients should keep track of calcium and vitamin D levels, adjusting their diet or treatment as needed to help prevent weak bones (osteoporosis) or fractures.
To prevent damage to the front of the eye (corneal abrasions) related to a condition where the eyelid turns outwards (ectropion), it’s beneficial for patients to have regular eye exams. Regular ultrasounds of the liver and annual liver function tests are also advised.
If the bone marrow is not producing enough blood cells, transfusions can provide temporary relief. In severe cases, a stem cell transplant could be considered, although it doesn’t have a high long-term survival rate. Medicines that promote blood cell development (androgens and granulocyte colony-stimulating factors, or G-CSF) can sometimes be used before a transplant. However, these have risks as well, including potential liver tumors or spleen rupture.
Patients should avoid harmful habits and activities such as smoking, heavy drinking, or excessive sun exposure without protection. Any necessary surgical treatments should be performed based on the patient’s individual case.
What else can Dyskeratosis Congenita be?
Rothmund-Thomson syndrome and a condition known as epidermolysis bullosa simplex with mottled pigmentation both have similar skin conditions to Dyskeratosis Congenita (DKC), as the skin becomes patchy in texture and color. The same kind of patterned skin darkening can also be seen in conditions like Dermatopathia pigmentosa reticularis and Naegeli-Franceschetti-Jadassohn syndrome. Fanconi anemia, which is caused by a genetic instability leading to changes in the structure of chromosomes, can present similar features as DKC. Another condition showing similar skin pattern changes is graft-versus-host disease, where the body’s immune system attacks its own cells, and can also present changes in the mouth lining that resemble a condition called lichen planus.
There are also specific versions of DKC which show the typical features of the disorder, but also have their unique characteristics. For instance, Hoyeraal-Hreidarsson syndrome is like DKC but also comes with underdeveloped cerebellum (a part of the brain) and growth restrictions before birth. Revesz syndrome, on the other hand, can be distinguished from other forms of DKC by underdeveloped cerebellum and a condition called exudative retinopathy, which affects vision.
What to expect with Dyskeratosis Congenita
People with a condition called dyskeratosis congenita typically have a shorter life expectancy. The most common causes of death, listed in order from most to least common, are a malfunctioning bone marrow, lung disease, and various types of cancer.
