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.
Have a combination of signs/symptoms suggestive of MEHMO syndrome,
Be a relative of an individual with MEHMO syndrome/eIF2-related condition and whose genetic may be informative for research.
Have a combination of signs/symptoms suggestive of MEHMO syndrome,
Be a relative of an individual with MEHMO syndrome/eIF2-related condition, AND a carrier of the pathogenic or likely pathogenic variant.
None
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.
Cohort
Other
Not listed
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.
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.
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.
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.
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.
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