Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study

Abstract

BackgroundRett syndrome is a severe neurodevelopmental disorder associated with mutations in the MECP2 gene. Irregular breathing patterns and abdominal bloating are prominent but poorly understood features. Our aims were to characterize the abnormal breathing patterns and abdominal bloating, investigate the distribution of these by age and mutation type and examine their impact and management from a caregiver perspective.MethodsWe invited previously recruited families from the International Rett Syndrome Study to complete a web-based questionnaire concerning their family member with Rett syndrome aged between 2 and 57 years. We used logistic regression to investigate presence, frequency and impact of breath-holding, hyperventilation, or abdominal bloating by age group and mutation type. Age of onset for both breathing abnormalities was investigated using time-to-onset analysis, and the Kaplan–Meier method was used to estimate the failure function for the study sample. Descriptive statistics were used to characterize the management of irregular breathing.ResultsQuestionnaires were returned by 413/482 (85.7%) families. Breath-holding was reported for 68.8%, hyperventilation for 46.4% and abdominal bloating for 42.4%. Hyperventilation was more prevalent and frequent in those younger than 7 years of age and abdominal bloating in those aged over 20 years. Onset of breathing irregularities usually occurred during early childhood. Caregivers perceived that daily life was considerably impacted for almost half (44.1%) of those with abdominal bloating and in just over than a third of those with breath-holding (35.8%) or hyperventilation (35.1%). Although perceived impact was broadly comparable between age and mutation groups for breath-holding, hyperventilation and abdominal bloating, girls and women with a p.Arg294* mutation were considered to be more affected by all three conditions. Only 31 individuals had received medically prescribed treatments including 12 different medications, added oxygen, rebreathing apparatus or non-invasive ventilation.ConclusionsAutonomic disturbances are prevalent and burdensome in Rett syndrome. This information may guide the design of inclusion criteria and outcome measures for clinical intervention trials targeting autonomic abnormalities. Further investigation of available treatments is necessary to delineate evidence-based management pathways.

Placebo‐controlled crossover assessment of mecasermin for the treatment of Rett syndrome

“…It is characterized by normal early development followed by regression, leading to loss of spoken language and/or purposeful hand use, gait abnormalities, and development of stereotypic hand movements. Other common features include growth retardation, seizures, breathing abnormalities, vasomotor disturbances, and abnormal behavior 1, 2, 3, 5, 6, 7, 8. The current standard of care is symptomatic management, with no available treatments aimed at ameliorating the cardinal symptoms of the disorder 9, 10, 11…”

“…Other common features include growth retardation, seizures, breathing abnormalities, vasomotor disturbances, and abnormal behavior. [1][2][3][5][6][7][8] The current standard of care is symptomatic management, with no available treatments aimed at ameliorating the cardinal symptoms of the disorder. [9][10][11] Our initial understanding of the neurobiological bases of the disorder, primarily from tissue sample studies of children affected by RTT, served as the foundation for early drug trials.…”

Respiratory morbidity in Rett syndrome: an observational study

“…In the same study, lung histology was investigated in a mouse model, and diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was identified in two of four MECP2 ‐mutant mice . These findings indicate structural lung pathology in addition to autonomic effects on breathing dysfunction …”

“…Study methodology has been previously described. 9 In brief, English-speaking families with a child with a confirmed clinical diagnosis 2 and a pathogenic MECP2 mutation were recruited from InterRett and invited to complete a questionnaire. 15 The questionnaire was administered using the Research Electronic Data Capture (REDCap) tool, with a paper format or telephone interview also available.…”

“…8 These findings indicate structural lung pathology in addition to autonomic effects on breathing dysfunction. 9 Comorbidities associated with Rett syndrome could each be associated with respiratory infections. Scoliosis, a prevalent comorbidity affecting three-quarters of individuals with Rett syndrome by 15 years of age, 10 can impair posture and mobility as well as digestive and respiratory functioning.…”