Study finds sensory changes are more severe in MECP2 duplication disorder patients than Rett patients


A recent clinical study conducted at Texas Children’s Hospital and Baylor College of Medicine has found patients with two related MECP2 (methyl CpG-binding proteins) disorders exhibit changes in sensory behavior and more importantly, that patients with MECP2 duplication disorder are more severely impacted than those with Rett syndrome. The study led by Dr. Ariel Lyons-Warren, an investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) and instructor in the Section of Pediatric Neurology and Developmental Neuroscience at Texas Children’s Hospital and Baylor College of Medicine, was published in Autism Research journal.

This is the first study to quantitatively analyze sensory changes in patients with MECP2 disorders, caused by changes in gene dosage of the MECP2 gene. Too little MECP2 in neurons causes Rett syndrome, commonly seen in girls whereas too much MECP2 causes MECP2 duplication syndrome, which occurs almost exclusively in males.

“It is difficult to conduct systematic studies to profile the sensory changes in these patients because they have severe intellectual disabilities and are not verbal,” Bernard Suter, MD, assistant professor of Pediatrics-Neurology at Baylor College, a child neurologist at the Blue Bird Rett Center at Texas Children’s Hospital and one of the lead authors of the study, said.

The researchers circumvented this issue by using the Sensory Experiences Questionnaire, a well-established short parent questionnaire. This assessment assigns specific subscores to hypersensory vs hyposensory changes and takes into account changes in various sensory modalities such as tactile, vision, spatial orientation, and hearing.

They assessed the sensory profiles of 50 female Rett individuals and 122 male MECP2 duplication individuals. 

“We found that all patients in both populations had sensory processing abnormalities in hypo- and hyper-sensitive behaviors,” said Davut Pehlivan, MD, assistant professor at Pediatrics-Neurology at Baylor College, a child neurologist at Texas Children’s and Duncan NRI. “Furthermore, we found that the sensory changes were not identical between the patients with these two MECP2 disorders – hypersensitivity to tactile and vestibular sensory processing and for both social and nonsocial stimuli were much more pronounced in children with MECP2 duplication syndrome than in Rett patients.”

“This study provides the first insights into sensory processing abnormalities in a gene dosage disorder. These findings will be invaluable to guide the development and testing of new treatments and interventions to improve outcomes and, hopefully, quality of life in these patients,” Dr. Lyons-Warren added. “Sensory behaviors could be one of the first biomarkers to change with drug treatments in these patients, making them a measurable biomarker to track in future clinical trials for these conditions.”

Other authors and their institutional affiliations can be found here. The study was funded by the International Rett Syndrome Foundation, Rett Syndrome Research Trust, National Institute of Neurological Disorders and Stroke, Doris Duke Charitable Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and MECP2 Duplication Foundation.

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