Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1. Issue 3 (17th January 2018)

• Record Type: Journal Article
• Authors: Piard, Juliette; Lespinasse, James; Vlckova, Marketa; Mensah, Martin A.; Iurian, Sorin; Simandlova, Martina; Malikova, Marcela; Bartsch, Oliver; Rossi, Massimiliano; Lenoir, Marion; Nugues, Frédérique; Mundlos, Stefan; Kornak, Uwe; Stanier, Philip; Sousa, Sérgio B.; Van Maldergem, Lionel
• Is Part Of: American journal of medical genetics. Volume 176:Issue 3(2018)
• Page Start: 668
• Page End: 675
• Publication Date: 2018-01-17
• Subjects: cutis laxa -- hyperostotic skeletal dysplasia -- Lenz–Majewski syndrome -- PTDSS1; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.38604
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz–Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly.