Clinical and molecular profile of Duchenne muscular dystrophy in a single center in Brazil

Background: Duchenne muscular dystrophy (DMD), a disease with X-linked recessive inheritance pattern, is one of the most severe forms of inherited muscular dystrophies, caused by mutation in DMD gene and leading to progressive muscle fiber degeneration and weakness. Progressive weakness results in loss of ambulation early, and death from respiratory impairment or cardiac dysfunction. Objective: To evaluate the clinical profile of patients with DMD, followed from 2000 to 2024. Methods: This is a cross-sectional and retrospective study carried out at the Muscle Section of a reference center in Brazil. Results: The medical records of 143 patients were reviewed. Patients had a mean age of 11 years old (2-23 years old). The average age at onset of signs/symptoms was 3 years of age (ranging from 6 months to 9 years). Patients had their diagnosis confirmed at an average of 6 years of age (ranging from 6-16 years). The mean first baseline serum CPK was 12,936. The main signs/symptoms of initial manifestation were: falls (40%), motor developmental delays (15%) and change in gait (10%). 3% had language developmental delay as first symptoms and 5% had serum enzymes elevation as first manifestation even without symptoms. Regarding the molecular profile, 62% had deletion of 1 or more exons, 14% duplication of 1 or more exons, 10% nonsense variant, 10% frameshift and 4% at the splice site. Regarding corticosteroids, the average starting age was 6.9 years old; 70% were using deflazacort while 25% were using prednisolone/prednisone, and 5% were not using it or did not have data in the medical record. 33% of patients had already lost the ability to walk, with an average age of loss of ambulation of 9.6 years old. 39% of patients had neurodevelopmental disorder: 49 (32%) patients had some degree of intellectual disability, 21 (13%) had Attention Deficit Hyperactivity Disorder (ADHD), 10 (6%) autism spectrum disorder (ASD), 4 (2%) oppositional defiant disorder (ODD). 13% had more than one neurodevelopment disorder. Only two patients had epilepsy, one of which was associated with another genetic variant. Conclusion: The study demonstrated a profile of young patients, with 76% of patients presenting deletion or duplication of one or more exons, a molecular profile similar to that described in the literature. The average age of diagnosis was late compared to other studies, and the period between the onset of symptoms and molecular diagnosis was relatively long, reflecting the difficulty for physicians in recognizing the condition in its earliest stages. Finally, there was a higher prevalence of cognitive/neurodevelopmental disorders in this cohort.