Dyskeratosis Congenita

What is Dyskeratosis Congenita?
Dyskeratosis Congenita is a rare genetic disorder characterised by bone marrow failure. It results in the bone marrow being unable to produce an adequate amount of blood cells. Although this is a congenital condition, meaning that it is present at birth, the symptoms of DC can present at any point, from adolescence to adulthood.

What causes Dyskeratosis Congenita?
Dyskeratosis Congenita occurs due to variants (changes) in genes that code for telomeres, protective structures found at ends of chromosomes that prevent them from fraying and degenerating. Variants in these genes lead to shortened telomeres, thereby impairing cell function and causing tissue damage.

How is Dyskeratosis Congenita passed on?
The way Dyskeratosis Congenita is inherited varies depending on the gene involved. X-linked inheritance, where affected individuals typically inherit the mutated gene from their mother, is the most common, though autosomal dominant or recessive patterns can occur. Occasionally, spontaneous gene mutations may occur.

What are the symptoms of Dyskeratosis Congenita?
Symptoms of Dyskeratosis Congenita can vary, but typically include:
• Skin abnormalities
• Nail malformations (nail dystrophy)
• White patches in the mouth and throat (oral leukoplakia)

The absence of characteristic symptoms does not exclude Dyskeratosis Congenita. Some individuals may experience other complications such as:

• Delayed development
• Bone marrow failure leading to anaemia and low platelet count
• Thinning and premature graying of hair
• Lung disease such as pulmonary fibrosis, a condition that leads to the scarring of the lungs thereby inhibiting its ability to oxygenate blood
• Liver disease
• Visual changes
• Dental issues such as decreased root/crown ratios
• Infertility
• Increased risk of certain types of cancers such as leukaemia

How do we diagnose Dyskeratosis Congenita?
Diagnosing Dyskeratosis Congenita involves a thorough clinical examination, family history evaluation, telomere length testing and genetic testing. A bone marrow biopsy may be obtained to check for marrow abnormalities.

How do we manage Dyskeratosis Congenita?
Unfortunately, there is no cure for Dyskeratosis Congenita currently. Managing Dyskeratosis Congenita is dependent on the individual and the progression of their condition. Current therapeutic options are supportive and utilise a multi-disciplinary team, including different healthcare professionals, to address the unique needs of each individual. They focus on managing symptoms and complications, which may include assessing organ function, monitoring blood counts, androgen therapy, supportive care like blood transfusions or bone marrow transplants, and lung therapies. Genetic counselling may also be provided to help individuals and their families understand the condition and to discuss family planning. Support from national support groups like DCAction may also be available.

Credits:

Sharan Reghunathan – University of Mancheser 5th year medical student

 

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