Dyskeratosis Congenita

Background and History: 

This is a group of conditions that have their onset at birth or shortly thereafter.  Signs and symptoms are found throughout the body, many of which are life threatening.  All are caused by rare gene mutations that impact the structure of chromosomes of a type often associated with aging.

Clinical Correlations: 

Evidence of this condition can be seen throughout the body, both internally and externally.  However, there is considerable variability from patient to patient.  Some children have evidence of the disease but the more serious manifestations are seen by young adulthood.  Most individuals have signs of premature aging such as grey hair and hair loss at a young age.  Far more serious, however, is the occurrence of bone marrow failure, scarring of the liver and lungs, and susceptibility to cancer, especially leukemia.   The nails and teeth may fail to develop normally.  There may be a lacy pattern to the normal pigmentation of the skin.  The oral tissues often develop white plaques.  The eyelids may become scarred and distorted and the cornea (windshield of the eye) likewise can become scarred and sometimes infected.  The eyelashes can be sparse and often the lashes drag across the cornea causing severe discomfort and additional scarring.  Most patients have normal intelligence but cognitive and developmental delays are present in a few individuals.

Genetics: 

Mutations in at least 7 genes can cause dyskeratosis congenita.  It is inherited in three major patterns: autosomal dominant (in which the condition is passed from an affected parent to each child with a 50% risk), autosomal recessive (both parents carry a single copy of the mutation and their children have a risk of 25% that each child will inherit the condition), and sex-linked recessive (only mothers transmit the disorder to their sons and females do not inherit it).

Diagnosis and Prognosis: 

The diagnosis is usually made by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, dentists, and many other specialists.  Lifespan is limited but highly variable depending upon the organs involved.  Among the life-threatening disabilities, failure of the bone marrow is the most responsible for premature death.

Patients with this condition require lifelong surveillance for cancer, eye disease, liver scarring and lung function.  Stem cell bone marrow transplantation can be lifesaving but its effectiveness is sometimes limited to a finite period of time.

Additional Information
Inheritance/Pedigree: 
Autosomal dominant
Autosomal recessive
X-linked recessive, father affected
X-linked recessive, carrier mother