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.
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.
Study Type
OBSERVATIONAL
Enrollment
200
service Génétique clinique Pitié-Salpêtrière / Trousseau
Paris, France
Characterization of the etiologies of MEGs associated with tumor risk in 200 children with or without NDD, who underwent genome sequencing.
The investigator will study the diagnostic performance, i.e. the proportion in the sample of class 4 (probably pathogenic) or 5 (pathogenic) variants according to the American College of Medical Genetics (ACMG) classification
Time frame: Within 6 Months after last patient inclusion
To compare the diagnostic returns of the 2 patient groups
Time frame: Within 6 Months after last patient inclusion
To establish a ranking of the yields of the 9 known MEG genes associated with tumor risk
The investigator will do a descriptive analysis of the number of variants, their relative and absolute frequency.risk
Time frame: Within 6 Months after last patient inclusion
To identify the nature and frequency of other genetic causes of MEG, apart from the 9 targeted genes
The investigator will do a descriptive analysis of the number of variants, their relative and absolute frequency.risk
Time frame: Within 6 Months after last patient inclusion
To establish genotype-phenotype correlations in the different etiologies found
A descriptive analysis will be performed without statistical assumptions.
Time frame: Within 6 Months after last patient inclusion
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