Extract
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].
Abstract
PAVMs are underrecognised in telomere biology disorders and present diagnostic and therapeutic challenges http://ow.ly/2lPc304eu0t
Acknowledgements
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.
Footnotes
Support statement: This work was supported by the intramural research programme of the National Cancer Institute (Rockville, MD, USA), National Institutes of Health (NIH; Bethesda, MD, USA), the National Heart, Lung and Blood Institute, NIH and the Translational Research Program at Boston Children's Hospital (Boston, MA, USA). Funding information for this article has been deposited with Open Funder Registry.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received May 19, 2016.
- Accepted September 7, 2016.
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