Case Report: A de novo NSD2 multiple exon deletion variant in a child with Rauch-Steindl syndrome

Rauch-Steindl syndrome (RAUST) is a very rare genetic syndrome caused by pathogenic variants in the NSD2 gene on chromosome 4p16.3. Its clinical phenotype resembles that of Wolf-Hirschhorn syndrome (WHS) but is generally milder. Using whole-exome sequencing (WES), we identified a novel de novo deletion spanning exons 6-22 of the NSD2 gene in a 6-year-old Chinese boy diagnosed with RAUST. The patient presented with facial dysmorphisms, language retardation, global developmental delay, autism, and hypotonia. These findings further support the notion that haploinsufficiency of NSD2 is a key mechanism in WHS and that molecular genetic testing provides a more accurate diagnosis for such patients. The novel variant reported here expands the known mutational spectrum of NSD2.