Dyskeratosis congenita Q82.8

Rare, hereditary "progeria-like" genodermatosis with premature ageing, which is characterized by the triad of hypo- or hyperpigmentation, onychodystrophy (beginning before the age of 5) and leukoplakia in addition to severe systemic involvement (neurological, gastrointestinal, dental, ophthalmological, pulmonological and skeletal changes). The incidence of malignancies is increased in these patients.

Autosomal-dominant, autosomal-recessive and X-linked recessive inheritance have been described.

• Autosomal-dominant inheritance is caused by mutations of the human telomerase RNA gene (see TERT gene below).
• Mutations of the dyskerin(DKC1) gene (gene locus Xq28) are inherited X-linked recessively (see also MAGE-A3).

The dysfunction of dyskerin , which determines the disease, can lead to a telomere maintenance defect and resulting proliferation arrest via an interaction with telomerase and the associated telomere shortening. This would explain the inhibition of the highly proliferative tissues skin and bone marrow.

As an early symptom, there may be lacrimation and conjunctivitis. Characteristic is the triad:

• Chronic paronychia with consecutive nail dystrophies up to complete loss of nails(anonychia).
• Whitish thickening ( leukokeratosis) of the oral mucosa, rarely also of the anal, vaginal and urethral mucosa.
• Extensive areas of reticular hyperpigmentation and redness, telangiectasias, diffuse atrophy of the skin, anetoderma-like foci similar to poikiloderma vascularis atrophicans.

In addition, palmo-plantar hyperkeratosis and hyperhidrosis, obstruction of the lacrimal orifices, and frequent blistering of the mouth and skin may be observed.

Concomitant symptoms: Frequent diseases of the hematopoietic system, e.g. neutropenia. See also Fanconi-Zinsser syndrome. Development of poikiloderma, ectropion, lacrimation, conjunctivitis, perlèche, anal fissures, urethral fissures with partial closure of the orifice. Other malformations of the eyes, bones, joints, heart, vessels or intestines are possible.

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