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.
Keywords: Hypoglycemia; Megalencephaly; Phosphatidylinositol 3-Kinases; Polymicrogyria.
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