Work

Pulmonary arteriovenous malformations: an uncharacterised phenotype of dyskeratosis congenita and related telomere biology disorders

Year: 2016

Type: article

Abstract: The telomere biology disorder (TBD) dyskeratosis congenita (DC) is a multisystem inherited bone marrow failure syndrome and cancer predisposition syndrome caused by germline mutations in telomere biology genes ( DKC1 , TINF2 , TERC , TERT , NOP10 , NHP2 , CTC1 , WRAP53 , ACD , RTEL1 and PARN ). The classic triad of reticular skin pigmentation, dysplastic nails and oral leukoplakia is diagnostic of DC [1, 2]. Leukocyte telomere lengths less than the first percentile for age measured by flow cytometry with fluorescence in situ hybridisation are consistent with DC in the presence of other phenotypic features [3]. Pulmonary fibrosis, a known complication of DC/TBD, occurs in ≥20% of patients [1]. Pulmonary arteriovenous malformations (PAVMs) in DC have been previously described in case reports or small case series in the context of hepatopulmonary syndrome (HPS) [4–9]. Presenting features of PAVMs may overlap with those of pulmonary fibrosis, including dyspnoea, orthopnoea, platypnoea, cyanosis and digital clubbing. HPS is described as pulmonary vascular dilatation due to liver disease of any cause (cirrhotic/noncirrhotic with/without portal hypertension), leading to deficient arterial oxygenation [10]. PAVMs are underrecognised in telomere biology disorders and present diagnostic and therapeutic challenges <http://ow.ly/2lPc304eu0t> This case series is the first completed research effort of the Clinical Care Consortium for Telomere Associated Ailments (CCCTAA), formed in 2013. We thank the patients, their families and the referring clinicians for their valuable contributions to this study.

Source: European Respiratory Journal

DOI: 10.1183/13993003.01640-2016