Open AccessClinical and genetic profile of Brazilian patients with dysferlinopathies – A retrospective study
Author(s) -
Igor Braga Farias,
Bruno de Mattos Lombardi Badia,
Gustavo Carvalho Costa,
Roberta Ismael Lacerda Machado,
Carolina Maria Marin,
Wladimir Bocca Vieira de Rezende Pinto,
Paulo Victor Sgobbi de Souza,
Acary Souza Bullé Oliveira
Publication year - 2021
Language(s) - English
Resource type - Conference proceedings
DOI - 10.5327/1516-3180.054
Subject(s) - dysferlin , asymptomatic , muscle biopsy , limb girdle muscular dystrophy , medicine , retrospective cohort study , muscular dystrophy , phenotype , asymptomatic carrier , pediatrics , pathology , genetics , biopsy , biology , gene
Dysferlinopathies are a group of conditions that are caused by mutations in the dysferlin gene. Objectives: To characterize the clinical phenotypes and genotypic spectrum of dysferlinopathies patients and to estimate the progression of functional and motor decline. Design and setting: Retrospective analysis of the medical records of patients followed up at our institution between 1995 and 2020. Methods: Patients were selected based on the following inclusion criteria:(i) Identification of a mutation defined as pathogenic in homozygosis or compound heterozygosis in the Dysf gene;or (ii)compatible clinical manifestations and decreased expression of dysferlin in immunohistochemistry on muscle biopsy. Classification of the phenotype was based on the first symptoms. Functionality was defined by the Gardner–Medwin & Walton(GMW) scale modified for dysferlinopathy. Results: 23 patients were included in the study. 16 were classified as limb-girdle muscular dystrophy autosomal recessive 2 (LGMDR2), 4 as Miyoshi muscular dystrophy, 2 as proximo-distal onset and 1 as asymptomatic hyperCKemia. Thighs adduction was the most affected movement in the first evaluation (mean strength=3). Plantar flexion was the movement with the greatest decline in strength(mean=-0.10 points on MRC/year;pT, Arg2042Cys and c.2643+1G>A, p.?(splicing), found 3 times each. There was no statistical difference in muscle strength in the first evaluation, motor and functional decline between the phenotypes. Conclusion: While LGMDR2 was the most common phenotype at onset, with the exception of asymptomatic hyperCKemia, there were not a clear difference in the pattern of progression between them.