Investigations of Individuals With MEHMO Syndrome or eIF2-Pathway Related Conditions
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.
⁃ 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
• 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
• OR
• Be a relative of an individual with MEHMO syndrome/eIF2-related condition, AND a carrier of the pathogenic or likely pathogenic variant.
• OR
• Be a non-affected, non-carrier family member of an individual with MEHMO syndrome or an eIF2-pathway related condition.