Dr. Steve Skinner and Dr. Steve Kaminsky have written the following paper  to bring awareness to Males with MECP2 mutations.  It is intended to empower and educate parents of boys and make others aware of their special community within the field of Rett syndrome and MECP2 mutations.  Please read excerpts from the paper below or click HERE to view the entire paper. 

Males with MECP2 Mutations

(Can males have Rett syndrome?)


Overview of Rett Syndrome

Initially, Rett syndrome was recognized only in females.  It was hypothesized that Rett syndrome was lethal in males.  This suggested that Rett syndrome was a sex-linked genetic disorder with the gene being localized on the X chromosome.   READ MORE

Understanding the MECP2 gene

Males only have one X chromosome and, only one MECP2 gene.  Thus, a male with a mutation in the MECP2 gene has that mutation present in their only copy of the MECP2 gene.  Therefore, the function of MECP2 is affected adversely in all cells in the male.  This is why males with MECP2 mutations present differently than females with MECP2 mutations.  Males that have a mutation that is similar to the typical mutation seen in females with Rett syndrome present with early onset and more severe clinical problems than females with classic Rett syndrome.  READ MORE

Explanations for males with MECP2-related disorders

Males with Rett syndrome and Klinefelter syndrome:  There have been rare males reported with the typical history of classic Rett syndrome.

Mosaicism as a cause of Rett syndrome in males:  Mosaicism basically is a term defining a mixture of two different populations of cells. 

MECP2-related severe neonatal encephalopathy:  Males that have one of the mutations that are typically seen in Rett syndrome usually present with earlier onset and more severe symptoms than females.

Males with MECP2 mutations and milder presentations (MECP2-related disorders):  With increased sequencing of the MECP2 gene, males are being identified with mutations in the MECP2 gene outside of the regions of the gene that are usually associated with classic Rett syndrome in females.  READ MORE

Life expectancy of males with MECP2 mutations

The life expectancy and the medical complications in males with MECP2 mutations depends a lot on the underlying mutation and/or other associated genetic problems.  READ MORE

Understanding clinical trials in males with MECP2 mutations

Currently there are active clinical trials for Rett syndrome and plans for new trials in the future.  At this time, all the clinical trials have been designed with eligibility criteria that are inclusive for females and have excluded males with MECP2 mutations from participating.  This has generally occurred as part of the study design in attempt to have a uniform genetic background that will allow investigators to determine the safety and effectiveness of the medication for Rett syndrome.  READ MORE

Challenges in including males in clinical trials

Males with Rett syndrome or MECP2-related disorders are very rare.  Recruiting sufficient numbers of males for clinical trials is a challenge.

Males with typical MECP2 mutations present earlier with more severe symptoms and a different clinical course than females with Rett syndrome.

Trial design and eligibility criteria typically exclude males with MECP2 mutations from the early clinical trials in Rett syndrome.  This is partly due to the challenges of having essentially two different patient populations within the same clinical trial.  READ MORE

Future for males with MECP2 mutations

Any success of the treatment trials for girls with Rett syndrome may be applicable to males with MECP2 mutations. Any approved therapy for Rett syndrome could be considered for compassionate use in males with MECP2 mutations.  Rettsyndrome.org is committed to continue to fund research that will impact quality of life for both boys and girls living with MECP2 mutations.  READ MORE


Special thanks to Dr. Steve Skinner, Dr. Steve Kaminsky and Mrs. Jenna Manz for their collaborative effort on this important paper.




 The following video was created by Ana Rosa at the Woodlands, TX 2016 Strollathon