ESPE Abstracts

Introduction: Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder first identified in 2013, characterized by features overlapping with Prader-Willi syndrome (PWS) but distinguished by unique symptoms, such as joint contractures and high rates of autism spectrum disorder (ASD). SYS is caused by pathogenic heterozygous variants in the paternally-derived MAGEL2 allele. We sought to describe a case series of three SYS patients, highlighting the diverse endocrine manifestations and developmental trajectories associated with this rare disorder.

Case Presentations: Patients 1 & 2: A pair of female fraternal twins presented immediately after birth with dysmorphic features, severe hypotonia, joint contractures, hypernatremia, hypoglycemic episodes, feeding difficulties and additional findings. They were found to harbor a de-novo heterozygous c.1958_1962delCGCCC variant in MAGEL2, confirming the suspected diagnosis of SYS. One twin passed away at the age of 1.7 years due to a pulmonary infection, while the surviving twin, now 4 years old, continued to exhibit severe developmental delay and required tracheostomy for respiratory stability. Patient 3: An infant with a de-novo pathogenic variant in MAGEL2 displayed dysmorphic features, increased muscle tone, and feeding difficulties. Endocrine evaluation revealed glucose instability at this stage without the need for treatment and deceleration in growth despite normal growth hormone (GH) levels. Global developmental delay was observed.

Discussion: SYS is associated with a high incidence of endocrine disorders, including central diabetes insipidus, GH deficiency, and hyperinsulinism. The clinical management of these cases required tailored endocrine interventions, underscoring the necessity for comprehensive monitoring and individualized treatment strategies. These findings reinforce the critical role of the MAGEL2 gene in brain development and endocrine regulation.

Conclusion: The distinct presentations of SYS in the case series illustrate the complexity of care required for infants and children with this unique condition and emphasize the need for heightened awareness among healthcare providers. Early and precise genetic diagnosis, coupled with vigilant endocrine surveillance, is essential for optimizing patient outcomes.