Dados do Trabalho

Título

CLINICAL AND MOLECULAR PROFILE OF DUCHENNE MUSCULAR DYSTROPHY IN A SINGLE CENTER IN BRAZIL

Introdução

Duchenne muscular dystrophy (DMD), a disease with X-linked recessive inheritance pattern, caused by mutation in DMD gene. Progressive weakness results in loss of ambulation early, and death from respiratory impairment or cardiac dysfunction.

Objetivo

Evaluate the clinical profile of patients with DMD.

Método

This is a cross-sectional and retrospective study carried out at the Muscle Section of a reference center in Brazil, to evaluate the clinical profile of patients with DMD, followed from 2000 to 2024.

Resultados

The medical records of 143 patients were reviewed. Patients had a mean age of 11 (2-23) years old. The average age at onset of signs/symptoms was 3 years of age (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.

Conclusão

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.

Referências

Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021 Feb 18;7(1):13. doi: 10.1038/s41572-021-00248-3. PMID: 33602943; PMCID: PMC10557455.
Venugopal V, Pavlakis S. Duchenne Muscular Dystrophy. 2023 Jul 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29493971.
AARTSMA-RUS, A. et al. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve, v. 34, n. 2, p. 135-44, Aug 2006. ISSN 0148-639X < https://www.ncbi.nlm.nih.gov/pubmed/16770791 >.
MERCURI, E.; BÖNNEMANN, C. G.; MUNTONI, F. Muscular dystrophies. Lancet, v. 394, n. 10213, p. 2025-2038, Nov 30 2019. ISSN 1474-547X< https://www.ncbi.nlm.nih.gov/pubmed/31789220 >.

Palavras Chave

Duchenne muscular dystrophy; disease progression; genotype-phenotype correlations