Dados do Trabalho

Título

EXCELLENT EVOLUTION IN CASE OF SEVERE CONGENITAL MYOPATHY

Apresentação do caso único

This case involves an infant, 1 year and 4 months old, the sixth child of a healthy, non-consanguineous couple, admitted to the service at 3 months of life due to acute respiratory failure. He exhibited developmental motor delays, with severe global hypotonia more pronounced at 20 days of life, hypoactive deep tendon reflexes, dysmorphisms, and dysphagia. He underwent prolonged invasive mechanical ventilation, progressing to non-invasive ventilation only during sleep. He receives a diet via gastrostomy and accepts pureed foods orally. With intense early stimulation, he achieved neurodevelopmental milestones by 1 year of age: sitting without support, moving in bed, babbling, and partial improvement of dysphagia. In the initial investigation, spinal muscular atrophy was ruled out, and creatine phosphokinase levels and neuroimaging were normal. Exome sequencing revealed a pathogenic alteration in heterozygous form in the ACTA1 gene (c.557A>G p.(Asp186Gly)), consistent with congenital myopathy type 2C (OMIM* 102610).

Discussão

Pathogenic alterations in the skeletal muscle alpha-actin gene (ACTA1) have been identified in heterogeneous phenotypes of congenital myopathies, most of which follow an autosomal dominant inheritance pattern and occur without a prior family history. Most are de novo mutation, in heterozygous form (90%), and present with the typical form of the disease, which is a milder phenotype with greater survival. The infant in question has a genotype consistent with congenital myopathy 2C, the severe infantile form of the skeletal muscle disorder characterized by severe congenital weakness, usually leading to death from respiratory failure within the first year of life. Clinically, neonates with this condition exhibit global hypotonia, lack of antigravity movements, and difficulties with feeding and/or breathing, often requiring enteral feeding and mechanical ventilation. This patient’s form, which is rare, results in severe motor delays, with reports of survival up to age 10. With recent advances in genetics, diagnostic practice and classification have increasingly relied on molecular results, reducing the need for invasive molecular biopsy procedures.

Comentários finais

Knowledge about the genomic alteration in individuals affected by neuromuscular disorders, now classified according to specific genetic mutations, allows for individualized prognosis, genetic counseling, and programming for potential therapies that are already established and future ones under study.

Referências

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Joureau B, de Winter JM, Conijn S, et al. Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3). Ann Neurol. 2018;83(2):269-282. doi:10.1002/ana.2514

Levesque L, Del Bigio MR, Krawitz S, Mhanni AA. A de novo dominant mutation in ACTA1 causing congenital nemaline myopathy associated with a milder phenotype: expanding the spectrum of dominant ACTA1 mutations. Neuromuscul Disord. 2013;23(3):239-242. doi:10.1016/j.nmd.2012.12.004

National Center for Biotechnology Information. ClinVar; [VCV001467132.3], https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV001467132.3 (accessed Ago. 13, 2024).

Nowak, K. J., Wattanasirichaigoon, D., Goebel, H. H., Wilce, M., Pelin, K., Donner, K., Jacob, R. L., Hubner, C., Oexle, K., Anderson, J. R., Verity, C. M., North, K. N., and 13 others. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nature Genet. 23: 208-212, 1999. [PubMed: 10508519, related citations] [Full Text].

ONLINE MENDELIAN INHERITANCE IN MAN. Actin, ALPHA-1, Skeletal Muscle; ACTA1. OMIM, [s.d.]. Disponível em: https://www.omim.org/entry/102610. Acesso em: 14 ago. 2024.

Palavras Chave

Hypotonia; congenital myopathy; ACTA1