An observational study in Intellectual Disability, Epilepsy and Hypogonadisms, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Recruiting at 1 site in United States. Open to participants aged 1 Week to 100 Years. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Observational
This observational natural history study will follow individuals with MEHMO (Mental disability, Epileptic seizure, Hypopituitarism/Hypogenitalism, Microcephaly, Obesity) syndrome or an eIF2-pathway related disorder, who have symptoms such as intellectual delay, seizures, abnormal hormone and blood sugar levels, and decreased motor skills.
No current treatment for these conditions is available. A major impediment to the testing of potential therapeutic interventions is the lack of well-defined outcome measures. This protocol seeks to identify biochemical and clinical markers to monitor disease progression, and better understand the natural history of these conditions.
Any person diagnosed with MEHMO syndrome or related conditions, who can travel to the NIH Clinical Center can participate in this study.
The study involves:
Study Description: This is a prospective natural history study of individuals who have MEHMO syndrome or eIF2-pathway related conditions, or who are carriers of EIF2S3-related conditions to generate hypotheses for further understanding of disease pathophysiology, diagnosis, prognosis, management, and treatment. The protocol aims to enroll and follow affected or carrier individuals longitudinally to establish a repository of concurrent evaluations and biomaterials, as well as to enroll unaffected individuals for collection of informative comparable data and samples.
Objectives:
Primary Objective:
Characterize the presentation of MEHMO syndrome and eIF2 pathway related conditions.
Secondary Objectives:
Endpoints:
Primary Endpoint:
Frequency and time-to-event of signs and symptoms.
Secondary Endpoints:
387 studies on the registry are indexed under Intellectual Disability; 105 are open to participants now.
This study's planned enrollment of 150 is close to the median of 150 across 125 observational studies indexed under Intellectual Disability.
Browse Intellectual Disability studies →Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 422 studies on the registry; 24 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 11 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria: An individual must be > 1-week of age if affected, or > 1-month of age if unaffected. For Screening: Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND no or inconclusive molecular testing. For Main Study: 1. Have a combination of signs/symptoms suggestive of MEHMO syndrome, AND disease-associated variant(s) or variant(s) of uncertain significance in one of the eIF2-pathway related genes OR 2. Be a first-degree relative of an individual with EIF2S3-related MEHMO syndrome, AND a carrier of the pathogenic or likely pathogenic variant. OR 3. Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition. Exclusion Criteria: Any individual who, in the opinion of the Investigators, is unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
To be eligible to participate in this study, an individual must meet the following criteria:
Be >= 1-week of age if affected, or >=1-month of age if unaffected.
For Screening:
Have a combination of signs/symptoms suggestive of MEHMO syndrome,
AND
no or inconclusive molecular testing.
OR
For Main Study:
Have a combination of signs/symptoms suggestive of MEHMO syndrome,
AND
disease-associated variant(s) or variant(s) of uncertain significance in one of the eIF2-pathway related genes
OR
Be a relative of an individual with MEHMO syndrome/eIF2-related condition, AND a carrier of the pathogenic or likely pathogenic variant.
OR
EXCLUSION CRITERIA:
Any individual who, in the opinion of the Investigators, is unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation will be excluded from participation in this study.
Individuals who have MEHMO syndrome or eIF2-pathway related conditions 1-week of age or older.
EIF2S3-variant carrier individuals 1-month of age or older.
Unaffected individuals 1 month of age or older who are 1st degree relative of an affected individual
Characterize the presentation of MEHMO syndrome and eIF2-pathway related conditions.
Frequency and time-to-event of signs and symptoms. These will allow systematic and potentially quantitative measures of disease presentation that can then be operationalized to develop disease rating scale(s) and correlative measures for candidate biomarkers.
Time frame: Ongoing
Identify disease-reflective fluid biomarkers
Difference and range of candidate fluid biomarkers level in affected vs. carrier vs. unaffected individuals. Sensitive or specific quantitative markers will allow for improved diagnosis, management, and treatment of MEHMO syndrome or eIF2-pathway related disorders.
Time frame: Ongoing
Develop a disease severity rating scale or classification algorithm.
A quantitative rating scale or classification algorithm that reflects other disease aspects will provide a standardized tool for communication amongst all involved in the clinical care and research of MEHMO syndrome or eIF2-pathway related disorders.
Time frame: Ongoing
Assess tolerability and feasibility of study evaluations.
Frequency of completed evaluations and reasons for non-completion will inform design of future trials for MEHMO syndrome or eIF2-pathway related disorders.
Time frame: Ongoing
Characterize EIF2S3-carrier phenotype.
Frequency and time-to-event of signs and symptoms at disease-relevant intervals will provide a systematic evaluation of EIF2S3- carrier phenotype.
Time frame: Ongoing
Establish a repository of participant data and samples for future research.
A repository of concurrently collected participant data and samples for future research will provide resources for future research towards understanding the disease and developing interventions.
Time frame: Ongoing
Plan to share: Undecided — Requests for sharing of relevant IPD for clinical management purpose or directly from the individual participant will be considered on case basis and are not guaranteed to result in sharing of IPD.
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