Phenotypic spectrum and genetic analysis in the fatal cases of Schaaf-Yang syndrome Two case reports and literature review

Rationale: Schaaf-Yang syndrome, a rare imprinted hereditary disease caused byMAGEL2variants, manifests as developmental delay/intellectual disability, neonatal hypotonia, feeding difficulties, contractures, and autism spectrum disorder. Patient concerns: Patient 1 and 2 were infant girls presenting facial dysmorphisms, contractures of interphalangeal joints, neonatal hypotonia, feeding difficulties, congenital heart diseases, and respiratory complications. Besides, Patient 2 presented with delayed psychomotor development. Diagnosis: Whole-exome sequencing was performed and heterozygous mutations of theMAGEL2gene were detected in the patients. They were diagnosed as Schaaf-Yang syndrome. Interventions: The patients received supportive treatment including mechanical ventilation, parenteral nutrition and gastric tube feeding. Outcomes: Whole-exome sequencing revealed de novo heterozygous c.1996dupC pathogenic mutations in theMAGEL2gene in the 2 patients. They died due to respiratory failure at the age of 20 days and 98 days, respectively. Lessons: Our results indicate thatMAGEL2variants can cause congenital heart disease and fatal respiratory complications, broadening the phenotypic spectrum and adding to the fatal cases of Schaaf-Yang syndrome. We highly suggest that theMAGEL2gene should be added to gene-panels or gene-filters in next-generation sequencing-based diagnostics, which is of great significance for early diagnosis and early intervention of Schaaf-Yang syndrome patients.