Neurodevelopmental, behavioral, and emotional symptoms in Becker muscular dystrophy

Abstract

Introduction: Becker muscular dystrophy (BMD) results in decreased dystrophin with implications for mental health.Methods: This is a retrospective case series of neurodevelopmental, behavioral, and emotional symptoms and respective pharmacotherapies of 70 patients with BMD.Results: Fifty-four (77.1%) patients exhibited at least one symptom, and 19 (27.1%) patients exhibited four or more symptoms. The most prevalent symptoms were specific learning disabilities or special education needs (31.4%), inattention/hyperactivity (35.7%), language/speech delays (35.7%), and emotional or behavioral dysregulation (38.6%). Fisher's exact tests indicated that anxiety was more prevalent with mutations upstream of exon 30 (P = .049), but the prevalence of other symptoms did not differ with respect to mutation sites. Similarly, the number of symptoms individual patients with BMD exhibited did not differ with respect to mutation sites. Seventeen (24.3%) patients required pharmacotherapy to manage symptoms.Discussion: Neurodevelopmental, behavioral, and emotional symptoms are prevalent in patients with BMD regardless of dystrophin gene mutation site. K E Y W O R D S Becker muscular dystrophy, behavioral, cognitive impairment, dystrophin, emotional, fluoxetine, genetics, learning disabilities, neurodevelopmental, pharmacotherapy 1 | INTRODUCTION Becker muscular dystrophy (BMD), the milder allelic variant of Duchenne muscular dystrophy (DMD), is the result of mutations of the dystrophin gene on the X-chromosome. 1 It falls along a spectrum of dystrophinopathies that range from the severe and fatal DMD, with loss of walking by age 13, to the milder BMD phenotypes, with ambulation into the adult years. 2 Phenotypic variations are well explained by the reading frame hypothesis, which posits that in-frame mutations maintaining the dystrophin gene's reading frame and resulting in partially functioning dystrophin proteins yield phenotypes indicative of BMD, whereas DMD stems from out-offrame mutations distorting the reading frame and resulting in paucity or absence of dystrophin protein. 3 However, exceptions do exist; point mutations and nonsense mutations are typically associated with DMD but may also be found in patients with BMD. 4 As dystrophinopathies exist on a spectrum, so too do discrete diagnoses. Becker MD subtypes include a severe presentation resulting in Abbreviations: BMD, Becker muscular dystrophy; CPK, creatine phosphokinase; DMD, Duchenne muscular dystrophy; GC, glucocorticoid therapy; IRB, institutional review board. would ideally be followed for a number of years to verify that their clinical course paralleled the expected course of BMD. To comment on inheritance of neurodevelopmental, behavioral, and emotional symptoms, it may also have been useful to report the percentage of patients with family histories of mental health symptoms on their maternal side, paternal side, or both. However, these data were not available during the course of this study. Cognitive dysfunction may be a presenting symptom of patients with BMD...

Developmental delay and neuropsychiatric comorbidities associated with Duchenne and Becker muscular dystrophy

“…A limitation of the study is that only 13% of patients had been assessed by a neuropsychologist and 24% by a mental health professional. As such, the majority of diagnoses were inferred from symptoms provided by patient or parental report . Despite this limitation, the frequency of learning disabilities (31% of patients) identified was similar to that of an earlier study .…”

“…Similar to another study, there was no clear relationship between the presence of neuropsychiatric symptoms in BMD and the site of mutations within the dystrophin gene . Given the challenges associated with studying rare diseases, namely relatively small cohorts and phenotypic heterogeneity, it remains unclear whether an association may be seen in a larger cohort of boys and young men with BMD.…”

“…Anxiety and/or obsessive–compulsive disorder features were each seen in about 20% of patients. Many of the patients demonstrated multiple comorbidities with 27% exhibiting at least four features . The authors also present data on the use of stimulant and nonstimulant medications and selective serotonin reupdate inhibitors as a surrogate measure of the neuropsychiatric symptoms being clinically significant and impairing patients' day‐to‐day functioning.…”

“…Consistent with an earlier study, neurodevelopmental abnormalities were common among their patients. Based on parental report or self‐report, with or without formal diagnosis, 77% of patients exhibited at least one neurodevelopmental symptom, including language or speech delays (36%), attention deficit disorder (inattention and hyperactive features, 36%), and/or autistic features (11%) . Anxiety and/or obsessive–compulsive disorder features were each seen in about 20% of patients.…”

The Neurocognitive and Behavioral Profiles of 3 Brothers With Becker Muscular Dystrophy

“…4 Additionally, the neurodevelopmental, behavioral and emotional problems in BMD are suggested to appear regardless of dystrophin gene mutation site. 7 The current case report evaluates the neurocognitive and behavioral profiles of 3 brothers with BMD having a similar dystrophin mutation, to clarify whether a genotype-phenotype relation may exist in BMD. We expect that the profiles of the brothers are similar.…”