PTOTSLPNarrative ReviewDevelopmental medicine and child neurology2025

MAGEL2 (patho-)physiology and Schaaf-Yang syndrome.

Tim Schubert, Christian P Schaaf

PMID 38950199

WHAT IT FOUND

Schaaf-Yang syndrome is diagnosed by a paternally inherited MAGEL2 variant and can cause hypotonia, feeding and breathing problems, joint contractures, developmental delay, autism, and endocrine dysfunction.

Treatment evidence is limited.

Key findings

01Schaaf-Yang syndrome is usually diagnosed by molecular genetic testing that finds a pathogenic variant in the paternally derived copy of MAGEL2.

02Reported features include hypotonia, respiratory distress, feeding difficulty, failure to thrive, and joint contractures in infancy, and developmental delay, intellectual disability, seizures, autism, and behavioural problems in childhood and adolescence.

03Symptomatic therapies listed for patients include speech therapy, psychotherapy and psychiatric treatment, physical therapy, gastrointestinal medications, gastric or nasogastric tube feeding, tonsillectomy or adenoidectomy, and continuous positive airway pressure, but they do not ease the overall impact of SYS.

STILL TO COME

How it was doneWhat they foundWhat it means for PTsWhat it means for OTsWhat it means for SLPs

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What it does not show

This is a review, not a new clinical study, so it does not test a therapy or provide original outcome data. Many mechanistic claims come from mice, rats, cells, or PWS comparisons rather than from people with SYS. The proposed gain-of-function effect of truncated MAGEL2 is not proven, because the truncated protein has not been investigated in patient tissue. Phenotype descriptions vary widely, so a feature described in the review may not appear in every patient. Treatment statements are limited: growth hormone is reported but needs prospective trials, and oxytocin and other strategies are not established for SYS.

Declared interests

The authors report no funding and no conflicts of interest.

The easy way to misread this

Do not read the listed therapies or growth hormone findings as proven treatment effects. This is a review of clinical descriptions, animal models, and proposed mechanisms. It is not a trial that shows that any therapy works.

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