Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type

Abstract

Purpose: The Ehlers-Danlos syndrome (EDS), dermatosparaxis type, is a recessively inherited connective tissue disorder caused by deficient activity of ADAMTS-2, an enzyme that cleaves the amino terminal propeptide domain of types I, II, and III procollagen. Only 10 EDS dermatosparaxis patients have been reported, all presenting a recognizable phenotype with characteristic facial gestalt, extreme skin fragility and. laxity, excessive bruisingand sometimes major complications due to visceral and vascular fragility. Methods: We report on five new EDS dermatosparaxis patients and provide a comprehensive overview of the current knowledge of the natural history of this condition. Results: We identified three novel homozygous loss-of-function Mutations (c.2927\_2928delCT, p.(Pro976Argfs{*}42)c.669\_670dupG, p.(Pro224Argfs{*}24)and c.2751-2A>T) and :one compound heterozygous mutation (c.2T>C, p.? and c.884\_887delTGAA, p.(Met295Thrfs26{*})) in ADAMTS2 in five patients from four unrelated families. Three of these displayed a phenotype that was strikingly milder than that of previously reported patients. Conclusion: This study expands the clinical and molecular spectrum of the dermatosparaxis type of EDS to include a milder phenotypic variant and stresses the importance of good clinical criteria. To address this, we propose an updated set:of criteria that accurately captures the multisystemic nature of the dermatosparaxis type of EDS.