Abstract
Objective: Weiss-Kruszka syndrome (WSKA; MIM#618,619) is a rare, autosomal dominant disorder associated with zinc finger protein 462 (ZNF462) gene variation or deletion of 9q31.2 involving ZNF462 and various congenital anomalies. Its specific clinical findings are abnormal facial shape, prominent forehead, high arched eyebrow, ptosis, delayed development of motor and language and mild global developmental delay. The prevalence of WSKA is only 25 individuals from literatures. Brain lesions related to WSKA are known as ventriculomegaly and middle line brain abnormalities like corpus callosum hypoplasia in about 25 percent of the patients. However, there have not been reported a patient who has structural malformation of pituitary gland with endocrine dysfunction. Here, we present a Korean boy molecularly confirmed as WSKA, having newly clinical manifestation of primary empty sella syndrome(ESS) associated with growth hormone deficiency(GHD).
Case Presentation: A 16-year-old boy visited to our hospital presented with severe short stature and delayed puberty. He also complained mild hypotonia, congenital both ptosis, mild intellectual disability. In the anterior pituitary combined test, GHD was diagnosed. In the brain magnetic resonance image, ESS was showed. With starting and continuing recombinant human growth hormone replacement therapy, to identify the underlying genetic cause, chromosomal microarray analysis and whole exome sequencing test were conducted. Finally, a heterozygous novel frameshift variant, c.4185del(p.Met1396Ter) in ZNF462 confirmed by Sanger sequencing, which had not been reported was identified
Conclusions: This is the first case of WSKA of an Asian with novel pathogenic variant of ZNF462 and new clinical features including primary ESS associated with GHD. This case could contribute to diagnosis of this syndrome, identify clinical features and provided novel insight into studies for the role of ZNF462 gene.
72 HIGH INCIDENCE OF PRIMARY EMPTY SELLA SYNDROME (PESS) IN CHILDREN WITH GROWTH HORMONE DEFICIENCY (GHD)
