Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Megalocephaly. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
EMeRiT: Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk
Overview
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.
Primary outcome measures
- Characterization of the etiologies of MEGs associated with tumor risk in 200 children with or without NDD, who underwent genome sequencing. [Time frame: Within 6 Months after last patient inclusion]
Secondary outcome measures (4)
- 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 [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 [Time frame: Within 6 Months after last patient inclusion]
- To establish genotype-phenotype correlations in the different etiologies found [Time frame: Within 6 Months after last patient inclusion]
Eligibility criteria
Inclusion criteria
- Patients with macrocephaly ≥ +3 DS due to brain MRI-confirmed MEG with or without NDD
- Patient with a proposal to investigate a genetic etiology by genome sequencing
- No objection by the patient's parents or guardians
- Patients affiliated to a social security scheme
Exclusion criteria
- Patients with an etiological diagnosis of its MEG
- Patients who have previously undergone genetic testing as part of their MEG, with or without a diagnosis
- Patients who have not received the standard-of-care genetic analysis, specifically whole genome sequencing
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- service Génétique clinique Pitié-Salpêtrière / Trousseau — Paris
Identifiers
NCT: NCT07142772 · APHP231309