Targeted syndrome under study:
Genes of the core component pathway with postzygotic or germline variants (with or without postzygotic loss-of-function mutations in the second allele):
PIK3CA (MIM*171834): MCAP (MIM#602501) and CLOVES (MIM#612918)
PIK3R2 (MIM*603157): MPPH (MIM#603387)
AKT3 (MIM*611223): MPPH (MIM#615937)
CCND2 (MIM*123833): MPPH (MIM#615938)
AKT1 (MIM*164730): Proteus syndrome (MIM#176920)
MTOR (MIM*601231): Smith-Kingsmore syndrome (MIM#616638) and FCD (MIM#607341)
PTEN (MIM*601728): Macrocephaly/autism syndrome (MIM#605309) and Cowden (MIM#158350)
Gene recently associated with segmental/focal overgrowth :
DEPDC5 (MIM * 614191): Epilepsy, familial focal (MIM#604364)
NPRL2 (MIM*607072): Epilepsy, familial focal (MIM#617116)
NPRL3 (MIM*600928): Epilepsy, familial focal (MIM#617118)
KPTN (MIM*615620): Intellectual developmental disorder (MIM#615637)
RPS6 (MIM*180460)
KICS2 (MIM*617420)
TBC1D7 (MIM*612655): Macrocephaly/megalencephaly syndrome (MIM#248000)
STRADA (MIM*608626): Polyhydramnios, megalencephaly, and symptomatic epilepsy (MIM#611087)
RHEB (MIM*601293)
Abstract
We recently reported on a French cohort of fetuses with segmental or focal overgrowth linked to variants in the PI3K/AKT/MTOR pathway.
To broaden our understanding, we aim to expand this cohort by including more cases of prenatally diagnosed segmental/focal overgrowth syndromes associated with constitutional or postzygotic variants in genes of the mTOR pathway, including PIK3CA, PIK3R2, CCND2, AKT1, AKT3, MTOR, PTEN, as well as recently identified genes such as GATOR (DEPDC5, NPRL2/3), KICSTOR, RPS6, STRADA, RHEB.
Our objectives are:
• To document prenatal, postnatal, and postmortem clinical data
• To explore clinico-biological correlations
• To collect fetal tissue samples for collaborative functional analyses.
We invite collaboration to enrich our cohort and advance research in this area.
Coordinating clinician
Nicolas BOURGON – nicolas.bourgon@aphp.fr
Institution
Fetal Medicine Unit, Necker University Hospital, Paris, France
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: No
2- Resampling of patients: Yes
3- Linked to a translational/basic research project: Yes