Schaaf-Yang syndrome is a rare genetic disorder affecting children that is caused by changes in the MAGEL2 gene but only if the change occurs in the version of the gene inherited from the father. Genetic diagnosis is often challenging because most MAGEL2 changes are new in the child (de novo), making it unclear which parental copy of the gene the change is on.
This study identified two unrelated infants with de novo MAGEL2 variants who had features of Schaaf-Yang syndrome and congenital hyperinsulinism, a condition causing low blood sugar from excess insulin. In both cases, long-read DNA sequencing confirmed the variants were on the copy of the gene inherited from the father. This established the diagnosis of Schaaf-Yang syndrome, demonstrating this method can be used to confirm diagnoses. It highlighted hyperinsulinism as an important, previously underrecognised feature of the condition. (https://jmg.bmj.com/content/early/2026/03/31/jmg-2025-111282)