Two siblings with Schaaf-Yang syndrome treated with growth hormone

Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder with overlapping features with Prader-Willi syndrome (PWS). We report two Japanese siblings with SYS harboring a rare MAGEL2 variant (NM_019066.5:c.1621C>T, p.(Q541*)). Both patients had GH deficiency and received GH therapy. The older sibling presented with neonatal hypotonia, joint contractures, and severe autism, while the younger sibling showed milder features but developed obesity and behavioral problems. GH therapy led to only modest improvement in their growth. The limited effect may have been related to the late initiation of treatment, marked non-adherence to therapy, and GH doses. This report highlights the phenotypic variability of SYS and demonstrates difficulties and potential issues of GH treatment as well as clinical response to GH treatment in this rare disorder.