mehmo natural history and biomarkers

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

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.

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: 1. identify disease-reflective fluid biomarkers 2. develop a disease severity rating scale or classification algorithm 3. assess tolerability and feasibility of study evaluations 4. establish a repository of participant data and samples for future research endpoints: primary endpoint: frequency and time-to-event of signs and symptoms. secondary endpoints: 1. mean difference of candidate fluid biomarkers level in affected versus carrier versus unaffected individuals 2. correlation of rating scale or classification algorithm to age, genotype, or other variables 3. frequency of completed evaluations and reasons for noncompletion study population: 25 affected individuals 1-week of age or older 25 eif2s3-variant carrier individuals 1-month of age or older 50 unaffected individuals 1 month of age or older of any sex, race, ethnicity, geographic location who can participate without increased risk to personal health.

Eligibility criteria:
* inclusion criteria: 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: 1. have a combination of signs/symptoms suggestive of mehmo syndrome, and no or inconclusive molecular testing. or 2. be a relative of an individual with mehmo syndrome/eif2-related condition and whose genetic may be informative for research. 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 relative of an individual with mehmo syndrome/eif2-related condition, 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 will be excluded from participation in this study.

Keywords: mehmo x-linked mehmo syndrome eif2-pathway related conditions eif2s3