DUCHENNE MUSCULAR DYSTROPHY - GENETICS: P.220A neuropsychological and neuroimaging study of female carriers of DMD mutations

Abstract

Dystrophinopathies are caused by DMD mutations and include Duchenne/Becker dystrophies. Men are typically affected, but subtle clinical signs have been increasingly reported in female carriers of DMD mutations (fcDMD) as well. Cognitive and cerebral abnormalities are major findings in affected men, but have not yet been assessed in fcDMD. Objectives: To investigate cognitive and neuroanatomical abnormalities in fcDMD. Fourteen fcDMD were submitted to neurological and neuropsychological examination, employing either the Addenbrooke's Cognitive Examination – Revised (ACE-R) test or the Montreal Cognitive Assessment (MoCA). For each subject, volumetric T1 cerebral sequences were obtained in a 3T MRI scanner. A control group of 14 age-matched healthy women was used for comparison. We computed cortical thickness measurements using the FreeSurfer software. Between-group comparisons were performed with GLM taking total intracranial volumes as covariates. Pearson coefficients explored associations between cognitive tests and MRI results. P values <0.05 were considered significant. Mean age and education of the fcDMD were 37.3±6.4 years and 8.5±3.6 years, respectively. None of the fcDMD presented muscular weakness or ECG abnormalities. Mean ACE-R and MOCA scores were 73.7±9.6 and 24.5±2.1. Half of patients (n=7) scored below the expected Brazilian and schooling-adjusted reference levels. Abnormal domains included attention/temporal orientation, language and visuospatial skills. MRI analyses revealed right inferior temporal cortical thinning in fcDMD, but it did not correlate with cognitive scores. fcDMD have cognitive and neuroanatomical abnormalities. Temporal regions look particularly vulnerable, but further studies are needed to fully characterize the structural pattern of damage in fcDMD.