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

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

Author information

1
Department of Neurology, Royal Children's Hospital, Melbourne, Australia; Victorian Clinical Genetics Service, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia. Electronic address: chloe.stutterd@mcri.edu.au.
2
Victorian Clinical Genetics Service, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Royal Women's Hospital, Melbourne, Australia.
3
Victorian Clinical Genetics Service, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia.
4
Murdoch Children's Research Institute, Melbourne, Australia; Department of Endocrinology, Royal Children's Hospital, Melbourne, Australia.
5
Victorian Clinical Genetics Service, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
6
Department of Pediatrics, University of Washington, Seattle, WA, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
7
Department of Neurology, Royal Children's Hospital, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.

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

PMID:
29883676
DOI:
10.1016/j.ejmg.2018.06.002
[Indexed for MEDLINE]

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