Clinical case of Wieacker–Wolff syndrome in a 5-year girl

Abstract

Wieacker–Wolff syndrome (WWS) (OMIM 314580, 301041) is rare, slowly progressive, X-linked hereditary disorder. It is characterized by fetal akinesia, which results in congenital multiplex arthrogryposis, spasticity, and development delay. WWS is caused by the point mutations or extended deletions in the ZC4H2 gene, located on the long arm of the X chromosome (Xq11.2). Currently, about 100 cases have been described. We present the case of WWS 5-year girl. DNA diagnostic was performed using full exome sequencing and confirmed by Sanger sequencing. Determination of non-random X-chromosome inactivation was performed by methyl-sensitive PCR of GAAA-repeat RP2 gene.  The main clinical symptoms in our case are stiffness of large and small joints, specific facial phenotype, spasticity and lack of independent walking. We revealed heterozygous mutation с.22_23delAT (p.Met8fs) in ZC4H2 gene. Non-random inactivation of the X chromosome was detected (XCI = 96.1%). Conclusions. Clinical symptoms of the disease, the nature of the detected mutation and the literature data indicate to the presence of an X-linked dominant pattern of inheritance of WWS in our patient. We described the case referred to the group of ZC4H2-associated rare disorders.