The Schaaf-Yang syndrome (SYS) is an autosomal dominant multi-system genetic disease caused by melanoma antigen L2 (MAGEL2) gene mutations imprinted by mothers and expressed by fathers on the 15q11-15q13 chromosomes in the critical region of Prader-Willi. MAGEL2 is a single exon gene and one of the protein-coding genes of the Prader-Willi domain. MAGEL2 is a matrilineal imprinted gene (i.e., the maternal chromosome is methylated). It is only expressed by unmethylated paternal alleles, and the individual is affected only when the variation occurs on the paternal allele.
We reported a patient with MAGEL2 gene new site mutation who had mild intellectual disability, social fear, small hands and feet, obesity issues, dyskinesia, growth retardation, language lag and sexual development disorder.
Whole-exome sequencing showed a heterozygous variation in the MAGEL2 gene, NM_019066.4:c.1687C > T (p.Q563X) and diagnosed as Schaaf-Yang syndrome.
Patient was advised to reduce weight, control blood lipids, blood glucose through appropriate strengthening of exercise and diet control in the future. At the same time, the family members were advised to provide mental training to the patient to strengthen the contact and communication with the outside world and improve the autistic symptoms. Because of the patient’s bilateral cryptorchidism, it is recommended that the patient should be treated with bilateral cryptorchidism reduction fixation.
After a follow-up of the patient for 2 months, the patient is still walking unsteadily and requires an auxiliary reference material to walk normally. There is no significant change in height compared to before, and the weight has dropped by about 2 kg in the past 2 months. The symptoms of autism have improved slightly. The patient is willing to communicate with outsiders; his intelligence has not improved significantly, and his academic performance in school is still at the middle and lower levels.
The pathogenesis of SYS is complex, involving multiple pathways such as Leptin-POMC, MAGEL2-USP7-TRIM27 complex and oxytocin. Our study has also found that certain fatal phenotypes such as respiratory distress have a high incidence at individual sites, and early detection and timely intervention may prolong the life span of patients. Therefore, for patients in whom SYS is highly suspected, gene detection should be carried out as soon as possible.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.