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Research paper

Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism

Pathogenic/likely pathogenic variants in PTEN, PIK3CA, MTOR, and PPP2R5D found in ~10 children selected for macrocephaly + DD/ASD; all PI3K-AKT-mTOR-positive children had megalencephaly on MRI and lower DQ than the rest of the cohort. Two had somatic mosaic PIK3CA variants detectable in blood at low mosaicism.

Indexed context

Yeung KS, Tso WWY, Ip JJK, et al.

pi3k-akt-mtorovergrowthmacrocephalypediatric-epilepsydevelopmental-delay

Markdown path

content/research/papers/2017-yeung-pi3k-akt-mtor-macrocephaly.md

Findings

Pathogenic/likely pathogenic variants in PTEN, PIK3CA, MTOR, and PPP2R5D found in ~10 children selected for macrocephaly + DD/ASD; all PI3K-AKT-mTOR-positive children had megalencephaly on MRI and lower DQ than the rest of the cohort. Two had somatic mosaic PIK3CA variants detectable in blood at low mosaicism.

Why it may matter for Levi

Directly supports ordering trio WES + CMA + methylation in Levi given symmetric overgrowth + DD + DEE-SWAS. The 9/9 megalencephaly-on-MRI rate among PI3K-AKT-mTOR-positive children in this cohort specifically argues for a neuroradiology re-read of Levi's MRI looking for subtle megalencephaly, cortical dysplasia, or bottom-of-sulcus dysplasia before de-emphasizing the pathway.

Paper text

Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism

Yeung KS, Tso WWY, Ip JJK, et al. — Molecular Autism (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5738835/

Findings summary

Pathogenic/likely pathogenic variants in PTEN, PIK3CA, MTOR, and PPP2R5D found in ~10 children selected for macrocephaly + DD/ASD; all PI3K-AKT-mTOR-positive children had megalencephaly on MRI and lower DQ than the rest of the cohort. Two had somatic mosaic PIK3CA variants detectable in blood at low mosaicism.

Relevance to Levi

Directly supports ordering trio WES + CMA + methylation in Levi given symmetric overgrowth + DD + DEE-SWAS. The 9/9 megalencephaly-on-MRI rate among PI3K-AKT-mTOR-positive children in this cohort specifically argues for a neuroradiology re-read of Levi's MRI looking for subtle megalencephaly, cortical dysplasia, or bottom-of-sulcus dysplasia before de-emphasizing the pathway.

Provenance

  • Ingested 2026-04-16 as part of the batch literature pass supporting the Root Cause Theories, diagnostics, and treatments workspaces.
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