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Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in <scp>PI3K‐AKT‐mTOR</scp> signaling pathway
- Source :
- Ultrasound in Obstetrics & Gynecology. 59:532-542
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K-AKT-mTOR signaling pathway.We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K-AKT-mTOR pathway genes by next-generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid.During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K-AKT-mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA-related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K-AKT-mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with PIK3CA variants. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
- Subjects :
- Hemimegalencephaly
Pathology
medicine.medical_specialty
Genetic counseling
Prenatal diagnosis
Germline
AKT3
Phosphatidylinositol 3-Kinases
Humans
Medicine
Radiology, Nuclear Medicine and imaging
Megalencephaly
PI3K/AKT/mTOR pathway
Retrospective Studies
Fetus
Radiological and Ultrasound Technology
business.industry
TOR Serine-Threonine Kinases
Obstetrics and Gynecology
General Medicine
medicine.disease
Reproductive Medicine
Mutation
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 14690705 and 09607692
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Ultrasound in Obstetrics & Gynecology
- Accession number :
- edsair.doi.dedup.....9356d5991ff3fb34585b740606453eb5