Dyskeratosis Congenita

Also known as: Hoyeraal-Hreidarsson syndrome; Zinsser–Engman–Cole syndrome


Dyskeratosis congenita is a genetic condition that can affect the skin, blood, eyes, teeth, bones, gastrointestinal tract (bowel), genitourinary (kidneys, bladder) and respiratory (breathing) systems.


Last updated July 2018 by Professor I Dokal, Professor of Paediatrics, Barts and The London, Queen Mary University, London, UK.

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What are the symptoms?

Children with the condition often have fingernails and toenails that grow poorly or are abnormally shaped. They also often have changes in skin colouring (pigmentation), especially on the neck and chest. White patches inside the mouth (oral leukoplakia) is another well-known characteristic of dyskeratosis congenita.

People with dyskeratosis congenita are especially vulnerable to impairment of bone marrow function (bone marrow failure). As the main function of the bone marrow is to produce new blood cells, affected individuals may develop aplastic anaemia (when the bone marrow does not produce enough new blood cells). They are also at higher than average risk for myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally and which may progress to a form of blood cancer called leukaemia. People with dyskeratosis congenita are also at increased risk of developing leukaemia in the absence of myelodysplastic syndrome. In addition, they have a higher than average risk of developing other cancers, especially cancers of the head, neck, anus or genitals.

People with dyskeratosis congenita may also develop pulmonary fibrosis, a condition that causes scar tissue (fibrosis) to build up in the lungs, decreasing the transport of oxygen into the bloodstream.

What are the causes?

In around 70 per cent of those affected, the condition is caused by mutations in the DKC1, TERC, TERT, NOP10, NHP2, TINF2, USB1, TCAB1, CTC1, RTEL1, ACD (TPP1), PARN and NAF1 genes. Twelve of these genes provide instructions for making proteins that help maintain telomeres, which are structures found at the ends of chromosomes and prevent genetic material being lost from the end of chromosomes. The genetic defects are not known in around 30 per cent of cases.

How is it diagnosed?

The condition will be suspected based on clinical features a person presents with. If the mutation(s) causing the condition is in one of the twelve known genes, then molecular testing (testing of DNA to look for the mutation) will confirm the diagnosis.

How is it treated?

There is no cure for dyskeratosis congenita, treatment will aim to reduce the symptoms. Patients who develop abnormalities in their bone marrow are at risk of life-threatening infections and bleeding. Approximately 70 per cent of patients respond (obtain a good haematological response) to the drugs danazol and oxymetholone. If the bone marrow failure is severe and there is a compatible bone marrow donor, treatment by bone marrow transplantation is possible.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Inheritance can be X-linked recessive (DKC1), autosomal dominant (TERC, TERT, TINF2, RTEL1 and NAF1) and autosomal recessive (NOP10, NHP2, TERT, USB1, TCAB1, CTC1, RTEL1, ACD and PARN). In approximately 30 per cent of patients the genetic basis remains unknown. In some cases the mutation is a new mutation (de novo) and it is not inherited; this is usually the case for TINF2 mutations.

Prenatal diagnosis
Molecular (DNA) testing can be carried out during pregnancy if the mutation in a family is known. It is available in the UK as part of the Dyskeratosis Congenita Registry at Barts and The London School of Medicine and Dentistry, London, UK.

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