MECP2 Variants in Males: More Common than Previously Appreciated.

BACKGROUND

To assess the age and MECP2 variants of recently identified males and set the stage for further study of clinical features in males.

METHODS

Genetic information on the specific MECP2 variant was acquired from the coordinator (K.F.) of the Parent Group for Males. Data were collected indicating whether these variants were de novo or transmitted from the mother and whether males who appeared to meet the diagnostic criteria for Rett syndrome had mosaicism for the MECP2 variant.

RESULTS

Fifty-nine males were identified through the parent group. Their ages ranged from 2 to 28 years, with the median age being 7.0 years and the mean age being 10.8 years. Of these variants, 46 (78.0%) were de novo, nine (15.3%) were maternally inherited, and for four (6.8%) inheritance was not known. Eleven (18.6%) were mosaic, 10 with somatic mosaicism and one with Klinefelter syndrome (47XXY). Together with males reported previously from the US Natural History Study, the total group represents 85 males, of whom 27 are deceased.

CONCLUSIONS

These data on males with MECP2 variants are important to caregivers, physicians, and researchers to begin to characterize their historical and clinical features, improve diagnostic recognition and overall care, and accelerate access to therapeutic studies including gene replacement strategies. Equal access to such therapies for males is critical.

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Ananth was a site PI for Acadia Pharmaceuticals and is the PI of the Center of Excellence Rett Syndrome Clinic at the University of Alabama at Birmingham. Dr. Fu was a site investigator for Acadia Pharmaceuticals and has received research support from the International Rett Syndrome Foundation. Dr. Neul has received research funding from the National Institutes of Health, the International Rett Syndrome Foundation (IRSF), and Rett Syndrome Research Trust (RSRT); offers personal consultancy for Acadia Pharmaceuticals Inc., Analysis Group, AveXis, GW Pharmaceuticals, Hoffmann-La Roche, Myrtelle, Neurogene, Newron Pharmaceuticals, Signant Health, Taysha Gene Therapies, and the preparation of CME activities for PeerView Institute and Medscape; serves on the scientific advisory board of Alcyone Lifesciences; is a scientific cofounder of LizarBio Therapeutics; and was a member of a data safety monitoring board for clinical trials conducted by Ovid Therapeutics. Dr. Benke has received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, Loulou Foundation, the National Institutes of Health, and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, Takeda Pharmaceutical Company Limited, and Taysha Gene Therapies; and clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. Dr. Marsh is site PI for Stoke therapeutics, Zogenix Pharmaceuticals, Acadia Pharmaceuticals, Marinus Pharmaceuticals, Takeda Pharmaceuticals, and Epygenix Pharmaceuticals. He has received research support from NIH, Penn Orphan Disease Center, International Rett Syndrome Foundation, International CDKL5 Research Foundation, and Curaleaf Inc.; is a consultant for Acadia Pharmaceuticals; and has prepared an educational program for Medscape. Dr. Suter has consultancy for Neurogene and Taysha with all remuneration paid to his department. He has been an investigator for clinical trials with Acadia Pharmaceuticals, Marinus, and Newron Pharmaceuticals. Ms. Ferdinandsen, Dr. Skinner, and Ms. Annese have nothing to report. Dr. Percy has received research support from the NIH and has been a site PI for Acadia Pharmaceuticals. He is a consultant for Acadia Pharmaceuticals, Taysha Gene Therapies, and Neurogene. He has prepared educational materials for WebMD, Medscape, Pharmacy Times Continuing Education, Prime Inc., and the CME Institute.