Morbidity and mortality in Schaaf-Yang syndrome


Schaaf-Yang syndrome (SYS), first described in 2013, is caused by pathogenic variants in the paternal allele of MAGEL2, one of the protein-coding genes in the Prader-Willi critical region on chromosome 15q11.2. Due to the phenotypical overlap with Prader-Willi syndrome (PWS), the disorder was initially termed “Prader-Willi-like syndrome”. As more patients were discovered, the phenotype caused by truncating pathogenic variants in MAGEL2 became increasingly distinct, and the name was changed to SYS. Today, more than 300 individuals with SYS have been identified. As SYS is a newly discovered neurodevelopmental disorder, the phenotypic spectrum is still being investigated and continues to expand. One of the most prevalent postnatal features of SYS is severe hypotonia, which contributes to respiratory and feeding difficulties. Developmental delay (DD) and intellectual disability (ID) become evident during childhood, with varying levels of severity. Hyperphagia, often seen in PWS, is also described for SYS, but appears to be less prevalent and has a later onset. A typical feature of SYS is autism spectrum disorder (ASD), which has been reported in three quarters of all patients. So far, the literature has focussed on characterizing the clinical phenotype of children and adults with SYS, but little is known about the early symptoms and clinical complications during the neonatal period. Huang et al. now report on a large cohort of neonates, highlighting the specific morbidities and the high mortality of young individuals with SYS.

In Annals of Translational Medicine