Polymicrogyria in association with hypoglycemia points to mutation in the mTOR pathway

Eur J Med Genet. 2018 Dec;61(12):738-740. doi: 10.1016/j.ejmg.2018.06.002. Epub 2018 Jun 5.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Animals
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Humans
  • Hypoglycemia / genetics*
  • Hypoglycemia / pathology
  • Infant
  • Male
  • Megalencephaly / genetics*
  • Megalencephaly / pathology
  • Mice
  • Mutation
  • Polymicrogyria / genetics*
  • Polymicrogyria / pathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt