Dyskeratosis congenita

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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Dyskeratosis congenita
Synonyms	Zinsser-Cole-Engman syndrome
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Specialty	Hematology, Genetics
Symptoms	Skin pigmentation, nail dystrophy, oral leukoplakia
Complications	Bone marrow failure, cancer, pulmonary fibrosis
Onset	Childhood or adolescence
Duration	Lifelong
Types	N/A
Causes	Genetic mutations (e.g., DKC1, TERT, TERC)
Risks	Family history
Diagnosis	Genetic testing, clinical evaluation
Differential diagnosis	Aplastic anemia, Fanconi anemia, idiopathic pulmonary fibrosis
Prevention	Genetic counseling
Treatment	Hematopoietic stem cell transplantation, androgen therapy, supportive care
Medication	Androgens, growth factors
Prognosis	Variable, depends on severity and complications
Frequency	Rare
Deaths	N/A

Dyskeratosis congenita (DC) is a rare, inherited disorder characterized by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia. It is a form of bone marrow failure syndrome and is associated with an increased risk of cancer and other medical complications.

Genetics

Dyskeratosis congenita can be inherited in an X-linked recessive manner, as well as in autosomal dominant and autosomal recessive patterns. The X-linked form is caused by mutations in the DKC1 gene, which encodes the protein dyskerin. Dyskerin is involved in the maintenance of telomeres, the protective caps at the ends of chromosomes.

Diagram of X-linked recessive inheritance pattern.

Clinical Features

The classic triad of clinical features in dyskeratosis congenita includes:

• Abnormal skin pigmentation: This often presents as reticular (net-like) hyperpigmentation, primarily on the neck and upper chest.
• Nail dystrophy: Patients may have thin, ridged, and brittle nails that may eventually be lost.
• Oral leukoplakia: White patches on the mucous membranes of the mouth that cannot be scraped off.

Additional features may include:

• Bone marrow failure: Leading to anemia, thrombocytopenia, and leukopenia.
• Pulmonary fibrosis
• Liver disease
• Increased risk of malignancies, particularly squamous cell carcinoma

Diagnosis

Diagnosis of dyskeratosis congenita is based on clinical findings, family history, and genetic testing. Telomere length measurement can also aid in the diagnosis, as patients with DC often have very short telomeres.

Management

Management of dyskeratosis congenita involves regular monitoring and supportive care. Treatment may include:

• Hematopoietic stem cell transplantation for bone marrow failure
• Regular dermatological and dental evaluations
• Surveillance for malignancies

See also

• Bone marrow failure syndrome
• Telomere
• X-linked recessive inheritance