Basilicata-Akhtar syndrome derived from a nullisomy of the MSL3 region in a Japanese boy

Abstract

  Basilicata-Akhtar syndrome is a rare X-linked disorder caused by a heterozygous or hemizygous pathogenic variant in MSL3 that results in global developmental delay apparent from infancy, feeding difficulties, muscular hypotonia. To date, approximately 40 cases have been reported. However, this disease has not been reported in Japan. Here, we report the first case of Basilicata-Akhtar syndrome in Japan. A 7-year-old Japanese boy presented with global developmental delay, hypotonia, and feeding problems. Physical examination revealed dysmorphic features including epicanthal folds, telecanthus, downslanted palpebral fissure, broad nasal bridge, anteverted nares, tented upper lip, lop ears, short hands and feet, tapered finger, genu valgum, pes planus, pectus carinatum, and scoliosis. Array comparative genomic hybridization analysis showed a nullisomy of the Xp22.2 region, including all coding region of MSL3 and only the 5’ region of ARHGAP6. The phenotypic characteristics of this patient were compatible with those previously reported in patients with Basilicata-Akhtar syndrome. His pathology was the deletion of all cording region of MSL3, leading to loss of function. Although there were two female cases of Basilicata-Akhtar syndrome with deletions of the all coding region of MSL3 and only the 5’ region of ARHGAP6, this is the first male case with a nullisomy of the same region. No differences in clinical presentation were observed between these three cases with the deletion and previously reported cases with single nucleotide variants of MSL3. Further cases from diverse ethnic groups with various variants are important to functionally characterize this syndrome.