X-linked dyskeratosis congenita: restrictive pulmonary disease and a novelmutation

Dyskeratosis congenita (DQ is a rare inherited multisystem disorder charact erised by lesions of the skin and appendages. Bone marrow failure occurs in 80% of patients. The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1. Pulmonary manifestations have rarely been r eported. It is not known whether there is a respiratory disease peculiar to these patients and, if so, whether it is associated with a specific geneti c mutation. A 40 year old Egyptian man with pulmonary disease and his sympt om free 35 year old brother both presented with mucocutaneous lesions chara cteristic of DC. Irk the older brother chest imaging revealed generalised i ntralobular interstitial thickening and honeycombing. Pulmonary function te sts showed a restrictive pattern. Open lung biopsy specimens of lung tissue showed various degrees of fibrosis consistent with usual interstitial pneu monia of chronic idiopathic pulmonary fibrosis. The younger brother was fre e of pulmonary lesions. Both had a novel missense mutation 5C -->T in exon 1 of the DKC1 gene. It is concluded that pulmonary disease in DC may be und erestimated, possibly because most patients die at an early age of bone mar row failure. No relationship between genotype and phenotype could be establ ished in the patients studied. The genetic diagnosis of DC is now available , which may enable it to be diagnosed in patients with restrictive pulmonar y disease and minimal cutaneous signs.