Lethal respiratory course and additional features expand the phenotypic spectrum of PIEZO2‐related distal arthrogryposis type 5. Issue 2 (1st November 2022)

• Record Type: Journal Article
• Authors: Oliwa, Agata; Hendson, Glenda; Longman, Cheryl; Synnes, Anne; Seath, Kim; Barnicoat, Angela; Hall, Judith G.; Patel, Millan S.
• Is Part Of: American journal of medical genetics. Volume 191:Issue 2(2023)
• Page Start: 546
• Page End: 553
• Publication Date: 2022-11-01
• Subjects: arthrogryposis -- lipid myopathy -- mechanosensation -- PIEZO2; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.63019
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: Distal arthrogryposes (DA) are a group of conditions presenting with multiple congenital contractures in the distal joints. The 10 types of DA are distinguished by different extra‐articular manifestations. Heterozygous gain‐of‐function variants in PIEZO2 are known to cause a spectrum of DA conditions including DA type 3, DA type 5, and possibly Marden Walker syndrome, which are usually distinguished by the presence of cleft palate (DA3), ptosis and restriction in eye movements (DA5), and specific facial abnormalities and central nervous system involvement, respectively. We report on a boy with a recurrent de novo heterozygous PIEZO2 variant in exon 20 (NM_022068.3: c.2994G > A, p.(Met998Ile); NM_001378183.1: c.3069G > A, p.(Met1023Ile)), who presented at birth with DA and later developed respiratory insufficiency. His phenotype broadly fits the PIEZO2 phenotypic spectrum and potentially extends it with novel phenotypic features of pretibial linear vertical crease, immobile skin, immobile tongue, and lipid myopathy.