Variable Phenotypes of ZC4H2-Associated Rare Disease in Six Patients

PurposeWieacker-Wolff syndrome is a rare disease caused by X-linked zinc finger C4H2-type containing (ZC4H2) mutations. It characterized arthrogryposis multiplex congenita (AMC) and intellectual disability (ID), including impairment of central peripheral synaptic plasticity. Currently, it named “ZC4H2-associated disease” (ZARD) due to various clinical features other than AMC ID. Here, we report six cases ZARD, describe their variable phenotypes.MethodsWe analyzed the detailed genotypes patients diagnosed whole-exome sequencing or chromosomal microarray.ResultsIn four male patients, hemizygous mutations were found (c. 245A>C in two c. 610C>A one patient, c.637C>T patient), all variants identified Sanger sequencing. In female 1.16-Mb deletion Xq11.2, ZC4H2, was microarray. All had heterogeneous phenotypes with severities. Motor delay observed whom could not walk independently. Other neurological included ID, spasticity, seizures. The craniofacial microcephaly, low-set ears, strabismus, ptosis, ocular motor apraxia, U-shaped upper lip vermilion, short neck, microretrognathia. most common musculoskeletal symptoms multiple arthrogryposis: metacarpophalangeal joint contracture, clubfoot, distal muscle weakness, Achilles tendon knee flexion camptodactyly, elbow hip subluxation.ConclusionThe ZARD prominent loss function showed more severe symptoms. Further research needed clarify phenotypic variability this disorder.