Molecular characteristics

Schaaf-Yang syndrome is caused by a mutation in the MAGEL2 gene.  If you think about our DNA as the letters in the alphabet, the mutation is typically a change of a single letter.  This single letter change causes a misspelling of the “words” made up by the alphabet.   In this case, the words making up “MAGEL2” is now disrupted and not readable.

The MAGEL2 gene is a maternally imprinted, paternally expressed gene.  Most people will get a copy of the gene from their mother and a copy from their father.  However, the copy we receive from our mother has marks on it that turn it off (silence it).  The copy we receive from our father is turned on. If that copy contains a mutation, there are no more good copies of the MAGEL2 gene.  This is the case for those with Schaaf-Yang syndrome.

In many cases, the MAGEL2 mutation that is found in the affected child is neither present in the father, nor the mother. This is considered a “de novo” mutation. In that case, the chances for future children to be affected with Schaaf-Yang syndrome is approximately 2-3%.
However, in some cases, the father of the affected child is found to carry the MAGEL2 mutation. He will be clinically unaffected if the mutation is present on his maternal copy (the gene copy he received from his mother). In this case, the chance of recurrence is then 50% for each future child. Prenatal genetic counselling is recommended.