ESPE Abstracts

Objective: To highlight the clinical characteristics and early genetic diagnosis of Schaaf-Yang syndrome (SYS).

Methods: Three cases were reported and related literature were reviewed.

Results: All the three patients were diagnosed with Schaaf-Yang syndrome attributing to the variation of MAGEL2 gene. Two of the patients predominantly presented as "language dysplasia", who was one 2 years and 6 months old boy (reported recently by us) and one 8 months old girl respectively. Another case was a newborn who was delivered by cesarean section because of fetal intrauterine distress. The Apgar score was 5 at the first minute. Her ears were relatively larger than normal infants without auricular, and her nasal root was higher. The newborn's fingers were overlapping and presented with clenched fists. Genetically, a de novo heterozygous c.1640-1641delTT mutation in MAGEL2 was detected on the boy, which was origin from his father. Bioinformatics analysis showed that a proline-to-arginine amino acid substitution in position 547 of the protein and early presented the stop codon at amino acid 165 behind the variation (p.Pro547Argfs*165). The 8 months old girl had a de novo heterozygous c.3745 C>T mutation in MAGEL2. Interestingly, her monther carried the same mutation but her father was not detected the specific genetic variations. Bioinformatics analysis showed that a arginine-to-cysteine amino acid substitution in position 1249 of the protein (p.Arg1249Cys). To our knowledge, both of the above variations have not been reported previously. For the newborn, a heterozygous c.1996dupC mutation in MAGEL2 was detected, and a frameshift mutation was found in the amino acid (p.Q666Pfs*47). Up to now, a total of 45 individuals suffered from SYS have been reported. Among these patients and our cases, the c.1996dupC mutation was the most common type which accounts for 40.4% (19/47), followed by c.1996delC and c.1912C>T, accounting for 10.6% (5/47) and 8.5% (4/47), respectively. It seems that the c.1996delC mutation has more severe clinical manifestations.

Conclusions: The c.1996dupC mutation was the most common type while the heterozygous c.1640-1641delTT mutation and c.3745 C>T mutation in MAGEL2 are novel variations which have not been described. For children with developmental delay, intellectual disability, neonatal hypotonia, feeding difficulties, joint contracture, and autism spectrum disorder, SYS should be considered after the exclusion of PWS. Gene analysis in MAGEL2 should be performed, which is of great significance for early diagnosis of SYS.