A newborn with a pathogenic variant in ASXL2 expanding the phenotype of SHAPNS: a case report and literature review

Abstract

Background: Shashi-Pena syndrome (SHAPNS) is a developmental disorder caused by mutations in additional sex combs-like Protein 2 (ASXL2). Since 2016, only 12 cases from 10 families have been reported. However, neonatal period characteristics remain largely unknown. Herein, we report a case with a pathogenic variant in ASXL2 in a newborn. Case Description: A newborn was diagnosed with a previously unreported de novo truncating mutation in ASXL2 (NM_018263.6) at 21 days and the clinical characteristics of all probands with ASXL2-related SHAPNS was reported in the literature. He had persistent hypoglycemia caused by inappropriate insulin levels and achieved stable glucose levels after octreotide treatment. Magnetic resonance imaging (MRI) revealed a small cerebellum, and fundoscopy showed bilateral retinal paving-stone-like white lesions. The results of trio-based whole exome sequencing (WES) were returned on the 21st day of life, and a heterozygous de novo truncating pathogenic c.1792C