Case Report: Schaaf-Yang Syndrome Milder Phenotype Due to Potential Pathogenic Novel Missense Variant as an Unusual Cause of Obesity in a Pediatric Patient.

Abstract

According to OMIM and Orphanet databases, Schaaf-Yang syndrome (SYS) (OMIM: 615547, ORPHA: 398069) is a rare genetic disorder that shares certain clinical features with Prader-Willi syndrome (PWS), including hypotonia, developmental delay, and early-onset obesity. However, SYS often exhibits a more complex and variable phenotype. Missense variants in MAGEL2 have been reported only rarely, and their phenotypic spectrum appears milder and more variable than that of truncating mutations. Data on early-onset obesity as a dominant feature in such patients are limited. In this case report, we describe a child with mild phenotype (SYS) carrying the novel missense variant MAGEL2(NM_019066.5):c.1265C>T (p.Pro422Leu) presenting with severe early-onset obesity and a comparatively neurodevelopmental phenotype. We present a case of a boy with neonatal hypotonia, diagnosed with (SYS) at age 9 years, with follow-up to age 11 years. The boy was born at 34+3 weeks of gestation with hypotonia, feeding difficulties, and a persistent ductus arteriosus that required surgical ligation in early infancy. In the following years, he developed severe early-onset obesity, already evident by age 2 despite multidisciplinary care. Genetic testing performed at age 9 years identified a novel missense variant (NM_019066.5)c.1265C>T in the MAGEL2 gene, which was not inherited from his mother, thereby confirming the diagnosis of (SYS). At the time of the most recent evaluation, at age 11 years, he remained under long-term follow-up. Clinical management over this period included endocrine therapy, cardiac surgery, physical rehabilitation, and dietary interventions, and despite the complexity of his condition, long-term stabilization of his BMI percentile was achieved with consistent non-pharmacological interventions. This case highlights the importance of early multidisciplinary investigation and intervention in SYS, particularly when obesity is the dominant feature. Effective long-term weight stabilization is possible through structured lifestyle management.