What are the IBMFS disorders?
Dyskeratosis Congenita (DC)
DC patients have characteristic abnormal shapes to fingernails and toenails, a lacy rash on the face and chest, and white patches in the mouth. More than half of the patients are males. About half of DC patients
develop bone marrow failure. Onset may be in early childhood, but
diagnoses are often made later, because the findings on physical
examination become more obvious with age and the complications increase with age. Several
have now been identified as causing DC, but there are more still
to be discovered.
- What are the major findings on physical examination?
- Abnormal fingernails and toenails (dyskeratosis)
- Lacy rash on the face, neck, and chest
- White patches in the mouth (leukoplakia)
- What is the age at diagnosis?
- From birth to 60 years of age or older
- The diagnosis is usually made between the ages of 10 to 30
- What is the pattern of bone marrow failure?
anemia is diagnosed when all 3 types of
are abnormally low because the bone marrow is not producing
(low red blood cell count) may develop (often with large red
- Low platelet count (platelets are the cells which help the
blood to clot)
- Low white cell count (white cells help the body fight off
- What specific kinds of
- Solid organ cancer
- Tongue, mouth and throat cancer ("head and neck")
- Cancer of the esophagus, stomach, colon, and rectum ("gastrointestinal")
- Perhaps others (all of the types of solid cancers associated
with DC have not been completely identified)
(cancer of the blood and bone marrow)
- How is DC specifically diagnosed?
- Characteristic findings on physical examination
- Telomere length testing (repeated sections of DNA at the ends of chromosomes are short in patients with DC).
- Mutation analysis (genetic testing)
- Laboratories can now identify the genetic "error"
in some patients.
- The type of DC that is inherited
only by males (X-linked inheritance) is usually due to mutations
in the gene called DKC1.
- The type of DC that is passed from an affected parent to
an affected child (autosomal dominant inheritance) may be due to mutations in other
called TERC, TERT and TINF2.
- Three genes have been identified for the type of DC
in which disease occurs only if a person has two
abnormal genes (autosomal
inheritance), NOP10 (also known as NOLA3), NHP2 (also known as NOLA2), and WRAP53.
- About 40% of patients have no mutations in the known genes; more genes await discovery.
- What are DC subsets?
- Hoyeraal-Hreidarsson (HH) Syndrome: Findings consistent with DC, plus intrauterine growth retardation, developmental delay, microcephaly (small head), cerebellar hypoplasia, immunodeficiency, and bone marrow failure. Some HH patients have mutations in DKC1 or TERT.
- Revesz Syndrome: Findings similar to HH, plus a specific finding in the eye, called “exudative retinopathy”, and calcifications in the head. One patient in our study had a mutation in TINF2.