Polymicrogyria in association with hypoglycemia points to mutation in the PI3K-AKT-mTOR pathway.

We report a 16-month-old male with congenital megalencephaly, polymicrogyria and persistent hypoglycemia caused by a mosaic PIK3CA pathogenic variant. Hypoinsulinaemic, hypoketotic hypoglycaemia is a rare complication of pathogenic variants in the PI3K-AKT-mTOR pathway genes including AKT2, AKT3, CCND2, PIK3R2 and PIK3CA, and has been identified in a PIK3CA mutant mouse model. Our case highlights the importance of considering PI3K-AKT-mTOR pathway variants as a cause for megalencephaly and cortical malformation when the phenotype includes hypoglycaemia. Recognizing the association of hypoglycemia with PI3K-AKT-mTOR pathway variants can provide a clue to the genetic basis of the cortical malformation. Patients with megalencephaly and a cortical malformation may be considered at risk of hypoglycaemia and monitored accordingly, at least until a PI3K-AKT-mTOR pathway variant has been excluded.
PMID: 29883676 [PubMed - as supplied by publisher]

Source: European Journal of Medical Genetics - June 5, 2018 Category: Genetics & Stem Cells Authors: Stutterd C, McGillivray G, Stark Z, Messazo B, Cameron F, White S, Mirzaa G, Leventer R Tags: Eur J Med Genet Source Type: research