ESPE Abstracts

Schaaf-Yang syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13. SYS is a neurodevelopmental disorder that has clinical overlap with Prader-Willi Syndrome in the initial stages of life, being the intellectual disability, developmental delay, autism spectrum disorder, neonatal hypotonia, infantile feeding problems, and distal joint contractures the most consistently shared features of patients with SYS. Endocrine changes include high levels of ghrelin, low IGF1 and growth hormone deficiency. Here we present 2 siblings, with clinical characteristics of SYS, one of them with a heterozygous MAGEL2 variant.

Case 1: A 6-year-old boy was born within normal weight and height Z score range. Since birth he had facial dysmorphisms, macroglosia, short stature, small hands and short feet, feeding difficulties with requirement of a nasogastric tube; hypotonia, intellectual disability, hypogonadism, temperature instability, obesity and chronic constipation. He then presented behavioral abnormalities. Laboratory results showed a low IGF1 level. A whole-exome sequencing was done in which a heterozygous MAGEL2 variant was detected: c2873G>Ap. (Trp958*) (NM 019066.4).

Case 2: A 4-year-old girl was born within normal weight and height Z-score range. She had the same facial dysmorphisms as her brother, macroglosia, short stature, small hands and short feet, hypotonia and intellectual disability. Laboratory results showed a low IGF1 level.

Conclusion: Our results indicate that testing for MAGEL2 variants should be considered in Prader Willi-like phenotype, as it exists a significant but incomplete overlap between these two syndromes, in order to achieve an early diagnosis of SYS, for genetic counseling, and for early intervention to manage its complex manifestations.