MAGEL2 and Schaaf-Yang Overview

Schaaf-Yang syndrome is a neurologic disorder caused by a disruption in the MAGEL2 gene. The MAGEL2 gene is located on chromosome 15. Each individual receives one copy of the gene from their biological mother and one from their biological father.  The MAGEL2 gene is a “maternally imprinted” gene, which means the copy received from the mother has a mark that turns off the gene. The copy received from the father does not have that mark and is turned on. Under normal circumstances, this is no problem. But if the copy received from the father has a mutation (disruption) in the MAGEL2 gene, it may lead to symptoms of Schaaf-Yang syndrome.

Schaaf-Yang syndrome was formerly called "Prader-Willi-like syndrome," due to the similarities these two syndromes share, which include hypotonia, global developmental delay/intellectual disability, sleep apnea, and feeding difficulties. However, patients with Schaaf-Yang syndrome have a relatively higher prevalence of autism spectrum disorder, joint contractures, and lowered bone density. As of December 2016, there are more than 80 individuals worldwide that have been diagnosed with Schaaf-Yang syndrome. 

Diagnosis of Schaaf-Yang syndrome

Schaaf-Yang syndrome is diagnosed through either whole exome sequencing or through MAGEL2 sequencing. These tests will examine if the mutation came from the maternal allele or through the paternal allele. For Schaaf-Yang syndrome, only the paternal allele is expressed, while the maternal allele is "silenced," so only mutations in the allele of MAGEL2 inherited from the father can lead to a diagnosis. Mutations can either be inherited from the father directly, meaning the father also has a copy of a mutated MAGEL2 allele, or they can be inherited de novoDe novo mutations mean that the father does not have a mutated allele himself, but rather that the mutation occurred as a new event in the sperm when the child was conceived. 

Recommended Tests 

In order to diagnose Schaaf-Yang syndrome, we recommend sequencing of the MAGEL2 gene. Once a mutation in MAGEL2 is found, testing should determine whether the mutation is on the paternal copy of the gene. Only mutations on the paternal copy can cause Schaaf-Yang syndrome. Mutations on the maternal copy are silent. 

The following tests are recommended for all patients with Schaaf-Yang syndrome:

Sleep Apnea Test/Sleep Study: Obstructive and/or central sleep apnea is present in many patients with Schaaf-Yang syndrome. It represents a major risk for the affected patients, especially in the early years of life.

Laboratory Tests:
1.       Fasting Glucose/Glucose Tolerance after 120 mins
2.       IGF-1/IGF-BP3
3.       FSH and LH
4.       TSH and T4
5.       Total Cholesterol
6.       Triglyceride
7.       HDL Chol
8.       LDL Chol
9.       Uric Acid

We also recommend an X-Ray to test for scoliosis and a DEXA scan of both hips and lower spine to test for bone density.

Additional Resources

More information may be found on the Schaaf-Yang Syndrome page of the Genetic and Rare Diseases Information Center website, and on the Schaaf-Yang Syndrome portal of the Foundation for Prader-Willi Research website.