Novel Pathogenic Variant in PIEZO2 in a Korean Patient with Distal Arthrogryposis

Abstract

Alterations in PIEZO2 can result in distal arthrogryposis, which is characterized by non-progressive contracture in two or more areas of the body prior to birth. Here, we present a 29-year-old man born with multiple joint contractures and cleft palate. He showed short stature, low-set ears, macrotia, hearing impairment, micrognathia, a triangular face, blepharophimosis, deep-set eyes, high arched eyebrows, decreased facial expressions, retrognathia, arachnodactyly, absent phalan-geal crease, shortening of the first and fifth toes, short stature, pectus excavatum, epicanthus, bi-lateral ptosis, and ophthalmoplegia. He also complained of dyspnea and severe kyphoscoliosis. Pulmonary function tests showed a severe restrictive pattern. An electrodiagnostic study did not reveal any neurogenic or myogenic features. Next-generation sequencing revealed a novel de novo heterozygous pathogenic variant in PIEZO2 (c.7251G>T; p.Trp2417Cys). Our study is the first report of a pathogenic variant in PIEZO2 in a Korean patient with distal arthrogryposis.