MEHMO Natural History and Biomarkers

NCT06019182 | Recruiting

• 2 other identifiers: 10001681001681-CH
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• General health assessment and evaluation
• Imaging studies
• Laboratory tests
• Collection of blood, urine, spinal fluid, skin biopsy.

Conditions

Microcephaly; Nervous System Malformations; Obesity; Epilepsy; Hypogonadisms; Intellectual Disability

Keywords

MEHMO; X-linked MEHMO Syndrome; eIF2-Pathway Related Conditions; EIF2S3

Outcome Measures

Primary Outcomes (1)

• 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.

  Ongoing

Secondary Outcomes (5)

• Identify disease-reflective fluid biomarkers

  Ongoing

• Develop a disease severity rating scale or classification algorithm.

  Ongoing

• Assess tolerability and feasibility of study evaluations.

  Ongoing

• Characterize EIF2S3-carrier phenotype.

  Ongoing

• Establish a repository of participant data and samples for future research.

  Ongoing

Study Arms (3)

Affected

Individuals who have MEHMO syndrome or eIF2-pathway related conditions 1-week of age or older.

Carrier

EIF2S3-variant carrier individuals 1-month of age or older.

Unaffected Non-carrier

Unaffected individuals 1 month of age or older who are 1st degree relative of an affected individual

Eligibility Criteria

• Age: 1 Week - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.
• Be a relative of an individual with MEHMO syndrome/eIF2-related condition and whose genetic may be informative for research.
• 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
• Be a relative of an individual with MEHMO syndrome/eIF2-related condition, AND a carrier of the pathogenic or likely pathogenic variant.
• Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Intellectual Disability; Epilepsy; Microcephaly; Nervous System Malformations; Obesity; MEHMO syndrome

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight

Study Officials

• An N Dang Do, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

An N Dang Do, M.D.

CONTACT

(301) 496-8849; an.dangdo@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: August 31, 2023
• Study Start: October 23, 2023
• Primary Completion (Estimated): September 1, 2053
• Study Completion (Estimated): September 1, 2053
• Last Updated: April 27, 2026

Record last verified: 2026-04-23

Locations

US (1)