NCT07142772

Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk

EMeRiT: Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: —

Summary

This study will show the value of early genetic diagnosis in the case of MEG in a child and may lead to recommendations aimed at preventing tumor risk based on a simple and easily accessible clinical criterion (the measurement of head circumference). Ultimately, this study may improve cancer prognosis in the population of children with MEG.

Detailed description

During paediatric follow-up, head circumference (CP) measurement can detect severe macrocephaly (CP ≥ +3 SD) in 1% of the population, in individuals with or without neurodevelopmental disorder (NDD). After prescribing brain imaging showing excess brain growth or megalencephaly (MEG), pediatricians can refer patients to expert centers (Rare Disease Reference Centers) for an etiologic search for MEG. Genome sequencing is then prescribed by pediatric neurologists or geneticists as part of the "cerebral malformations" pre-indication (Plan France Genomic Medicine 2025). In the literature, more than 70 genetic causes of MEG have been identified, 9 of which are responsible for pathologies associated with a sufficiently high tumor risk (\>5%) to justify recommendations for regular screening, specific to each pathology ((Cowden, Simpson-Golabi-Behmel syndrome, Gorlin syndrome, neurofibromatosis type 1, variant in the DICER1 gene). These genetic diseases are inconsistently associated with NDD (about 50%) and require specific follow-up to improve the oncological prognosis. The absence of an etiological diagnosis in these patients is potentially damaging and represents a theoretical loss of opportunity with regard to tumor risk. There are no large studies investigating the etiologies of MEGs, so the incidence of pathologies with tumor risk in this population remains unknown, with the exception of PTEN gene mutations, identified in 10% of patients with TND and MEG. This study will indicate the incidence of mutations in genes with tumor risk, which may eventually justify modifying current paediatric practice by recommending early etiological testing for MEGs.

Conditions

• Megalocephaly

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-09-01
• Completion: 2027-09-01
• First posted: 2025-08-27
• Last updated: 2025-08-27

Locations

1 site across 1 country: France