MegalocephalyEMeRiTNCT07142772
Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk
An observational study of Megalocephaly, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Megalocephaly
- How many people
- 200 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2025to Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Child, Adult, Older adult
Study population: Children having macrocephaly ≥+3 SD due to brain MRI-confirmed MEG, with or without neurodevelopmental disorders, who have undergone genome sequencing
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
service Génétique clinique Pitié-Salpêtrière / Trousseau
Paris, 75013
Solveig HEIDE, Doctor, 01 42 16 14 69, solveig.heide@aphp.fr
Cyril MIGNOT, Doctor, 01 42 16 13 47, cyril.mignot@aphp.fr
About this study
Official title: EMeRiT: Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk
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.
Read the 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
- Keywords
- Megalencephaly, tumor, Etiology
- Medical subject headings
- Megalencephaly, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Children having macrocephaly with or without neurodevelopmental disorders | Children having macrocephaly ≥+3 SD due to brain MRI-confirmed MEG, with or without neurodevelopmental disorders, who have undergone genome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 6 Months after last patient inclusion
Secondary outcomes (4)
To compare the diagnostic returns of the 2 patient groups
Measured: 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
Measured: 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
Measured: 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.
Measured: Within 6 Months after last patient inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2025
- Study startSep 2025 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MegalocephalyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Solveig HEIDE, medical doctor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07142772
- Sponsor's protocol ID
- APHP231309
- Acronym
- EMeRiT
- Status last verified
- Aug 2025
- First submitted
- 23 Apr 2025
- Last updated
- 27 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EMeRiT: Quantitative Assessment of the Etiologies of Megalencephaly Associated With a Detectable Tumor Risk
- ClinicalTrials.gov ID
- NCT07142772
- Acronym / sponsor ID
- EMeRiT / APHP231309
- Conditions
- Megalocephaly
- Keywords
- Megalencephaly, tumor, Etiology
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2025 (estimated)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 27 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children having macrocephaly with or without neurodevelopmental disorders | – | –Children having macrocephaly ≥+3 SD due to brain MRI-confirmed MEG, with or without neurodevelopmental disorders, who have undergone genome sequencing |
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- Children having macrocephaly ≥+3 SD due to brain MRI-confirmed MEG, with or without neurodevelopmental disorders, who have undergone genome sequencing
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
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
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Solveig HEIDE, medical doctor principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Megalocephaly, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Solveig HEIDE, medical doctor (01 42 16 14 69, solveig.heide@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025; AzTrials last refreshed its copy on 8 Nov 2026.