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Dyskeratosis Congenita – A Rare Bone Marrow Failure Syndrome!

Oral Leukoplakia Did you come across a child or an adult with abnormally shaped fingernails and/or toenails (dyskeratosis)? Or have you seen a person with ‘lacy’ pigmentation on the neck and chest? Or did you happen to notice white patches inside the mouth (oral leukoplakia) of a person while speaking? Ever wondered what condition could they be suffering from? Well, these three characteristic features belong to a rare genetic but severe bone marrow failure condition known as Dyskeratosis Congenita (inborn, irreversible degeneration of the skin tissue) or Zinsser-Engman-Cole syndrome.

You will be surprised to know that this condition affects approximately 1 individual in 1 million individuals. Moreover, men are more likely to develop it. 75% of the patients diagnosed with it are males.

Bone marrow is the originator of all different types of blood cells which are required for carrying out major blood related activities such as carrying oxygen to different body parts, acting as the body’s defense barrier etc.  Bone marrow failure or impairment of bone marrow functioning is the inability of the bone marrow to produce required number of blood cells, which in turn may lead to several health disorders.

Abnormalities & Disorders Involved:

Individuals with this syndrome may also develop some other health conditions such as:

  • Aplastic anemiaresult of inadequate blood cell production in the bone marrow.
  • Myelodysplastic syndrome a condition characterized by the inability of immature blood cells to transform into mature blood cells such as red blood cells, white blood cells and platelets. The pile up of the immature cells may progress to leukemia.
  • Cancers of neck, head and, genitals or anus.
  • Pulmonary fibrosisa condition in which scar tissue piles up in the lungs of the patient there by reducing the level of oxygen transported into the blood.

Abnormalities include:

  • Premature graying of hair or hair loss.
  • Abnormal eye parts such as narrow tear ducts that may not allow the eyes to drain the tears, which in turn results in the irritation of the eyelids.
  • Osteoporosis or very low bone mineral density.
  • Dental problems.
  • Liver disease.
  • Avascular necrosis or degeneration of the shoulder and hip joints.
  • Urethral stenosis in men. Urethra is the tube that transports urine from the bladder to out of the body. Stenosis means narrowing of the tube. This condition may lead to infections of the urinary tract due to difficulty in urination.

Genes Involved In Dyskeratosis Congenita:

Telomeres are the protective caps at the ends of the chromosomes. In more than half of the people suffering from this syndrome, genes responsible for the structural maintenance of the telomeres such as DKC1, TERT, TINF2 and TERC were mutated (mutation – permanent change in the sequence of DNA).

People who developed this condition without any mutations in these genes might have the involvement of other ‘telomere maintenance’ genes.

Inheritance Pattern:

Before getting an insight into the pattern of inheritance let’s have a look at the types of chromosomes in males and females, and the modes of inheritance.

S.No. Gender Chromosome
1. Male XX
2. Female XY

Autosomal dominant inheritance means one copy of the mutated gene in each cell is enough for the syndrome development.

Autosomal recessive inheritance means both the gene copies in each cell will have to be mutated.

The inheritance pattern depends on the gene that has been mutated.

  • DKC1 gene mutation leads to the inheritance of this syndrome in an X-linked recessive pattern. This gene is located on the X chromosome. Therefore, one modified copy of gene in each cell is enough to cause the condition in males. But, in females the condition develops only when both the gene copies are mutated which is very unlikely to happen. Hence, males are more affected with this type of inheritance pattern when compared to females.
  • A mutation in TERT gene leads to the inheritance of the disorder either in an autosomal recessive or autosomal dominant form.
  • TINF2 or TERC gene mutation leads to the inheritance of the syndrome in an autosomal dominant form.

Telomere length testing and mutational analysis are the 2 key diagnostic tools that confirm the diagnosis of the syndrome.

Research is being done to identify all the genes involved in the development of Dyskeratosis Congenita and other causes that lead to this life-threatening condition.

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