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CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(12): s00441792096
DOI: 10.1055/s-0044-1792096
Original Article

A self-reported Brazilian registry of 5q-spinal muscular atrophy: data on natural history, genetic characteristics, and multidisciplinary care

Um cadastro brasileiro autorrelatado de atrofia muscular espinhal 5q: dados de história natural, características genéticas e cuidados multidisciplinares
Rodrigo Holanda Mendonça 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil.
,
Juliane Suellen Arndt de Godoi 
2   Instituto Nacional da Atrofia Muscular Espinhal, São Paulo SP, Brazil.
,
Edmar Zanoteli 
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil.
› Author Affiliations Support The authors declare that they received financial support from Novartis Biociências and Roche Pharmaceuticals to conduct the present study.
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Abstract

Background Spinal muscular atrophy linked to chromosome 5q (SMA-5q) is a neurodegenerative disorder caused by mutations in the SMN1 gene.

Objective To describe the key demographic, clinical and genetic characteristics, as well as natural history data of patients with SMA-5q.

Methods Up to January 2022, 706 patients with confirmed genetic diagnosis of SMA-5q, or their parents, completed a self-reported questionnaire on natural history, genetic characteristics, drug treatments, and multidisciplinary care.

Results Most patients had type 1 SMA-5q (42%); with 33% having type 2, and 23% type 3. There were 667 patients (94.4%) with a homozygous SMN1-exon 7 deletion. Of the total, 131 (18.6%) patients had a previous family history of the disease, and the familial recurrence rate was higher in type 3 (25.6%). Type 1 patients had a mean age of 3 months at the onset of symptoms and a delay of more than 3 months until genetic diagnosis. The median survival of patients with type 1 without invasive ventilation was 27 months. Before 2018, the median age of use of invasive ventilation was 16 months and, after, most patients (71%) were not submitted to invasive ventilation. About 50% of patients with type 3 lost their walking ability by 37 years of age. Further, 384 (54.4%) patients had access to disease-modifying therapy, and 62.3% of type 1 patients were in treatment, compared with only 47.2% of type 2 and 31.9% of type 3 patients.

Conclusion There is still a substantial diagnostic delay, especially in those patients with types 2 and 3 SMA-5q. However, the present study demonstrated prolonged survival, especially in type 1 patients.

Resumo

Antecedentes A atrofia muscular espinhal ligada ao cromossomo 5q (AME-5q) é uma doença neurodegenerativa causada por mutações no gene SMN1.

Objetivo Descrever as principais características demográficas, clínicas e genéticas, assim como dados de história natural de pacientes com AME-5q no nosso meio.

Métodos Até janeiro de 2022, 706 pacientes com diagnóstico genético confirmado de AME-5q, ou seus pais, preencheram questionário sobre dados de história natural, características genéticas, tratamento medicamentoso e cuidados multidisciplinares.

Resultados A maioria dos pacientes tinha AME-5q tipo 1 (42%); 33% tinham tipo 2 e 23% tipo 3. Deleção homozigótica no SMN1 foi notada em 667 pacientes (94,4%). Do total, 131 (18,6%) pacientes tinham história familiar prévia, e a taxa de recorrência familiar foi maior no tipo 3 (25,6%). Os pacientes com tipo 1 tinham idade média de 3 meses no início dos sintomas e atraso de mais de 3 meses até o diagnóstico genético. A sobrevida mediana de pacientes com tipo 1 sem ventilação invasiva foi de 27 meses. Antes de 2018, a idade mediana de uso de ventilação invasiva era de 16 meses e, após, a maioria dos pacientes (71%) não foi submetida a ventilação invasiva. Cerca de 50% dos pacientes com tipo 3 perderam a marcha em média aos 37 anos de idade. Além disso, 384 (54,4%) pacientes tiveram acesso a alguma terapia modificadora da doença; 62,3% dos pacientes tipo 1 estavam sendo tratados, comparados a 47.2% do tipo 2 e 31.9% do tipo 3.

Conclusão Ainda existe um atraso substancial para o diagnóstico, especialmente nos pacientes com AME-5q tipos 2 e 3. Contudo, o presente estudo demonstrou sobrevida prolongada em pacientes tipo 1.

Keywords

Muscular Atrophy, Spinal - Survival of Motor Neuron 1 Protein - Natural History - Registries

Palavras-chave

Atrofia Muscular Espinal - Proteína 1 de Sobrevivência do Neurônio Motor - História Natural - Sistema de Registros

Authors' Contributions

RHM: data acquisition, study conception and design, and review and approval of the final version of the manuscript; JSAG: data acquisition and study conception; EZ: study design and review and approval of the final version of the manuscript.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Paulo José Lorenzoni.




Publication History

Received: 09 May 2024

Accepted: 11 August 2024

Article published online:
20 December 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Rodrigo Holanda Mendonça, Juliane Suellen Arndt de Godoi, Edmar Zanoteli. A self-reported Brazilian registry of 5q-spinal muscular atrophy: data on natural history, genetic characteristics, and multidisciplinary care. Arq Neuropsiquiatr 2024; 82: s00441792096.
DOI: 10.1055/s-0044-1792096
 

  • References

  • 1 Munsat TL, Davies KE. International SMA consortium meeting. (26–28 June 1992, Bonn, Germany). Neuromuscul Disord 1992; 2 (5–6): 423-428
    CrossrefPubMedSearch in Google Scholar
  • 2 Lefebvre S, Bürglen L, Reboullet S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995; 80 (01) 155-165
    CrossrefPubMedSearch in Google Scholar
  • 3 Finkel RS, McDermott MP, Kaufmann P. et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 2014; 83 (09) 810-817
    CrossrefPubMedSearch in Google Scholar
  • 4 Piepers S, van den Berg LH, Brugman F. et al. A natural history study of late onset spinal muscular atrophy types 3b and 4. J Neurol 2008; 255 (09) 1400-1404
    CrossrefPubMedSearch in Google Scholar
  • 5 Sugarman EA, Nagan N, Zhu H. et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet 2012; 20 (01) 27-32
    CrossrefPubMedSearch in Google Scholar
  • 6 TREAT-NMD SMA Registries Core Dataset version 1. TREAT-NMD. 2018 . Aug 31. https://treat-nmd.org/wp-content/uploads/2019/06/SMA-Full_Expanded_SMA_Core_Dataset.pdf . Accessed 20 Jun 2021
    Search in Google Scholar
  • 7 Monges S, Rosa AL. Management of neuromuscular diseases and spinal muscular atrophy in Latin America. Gene Ther 2017; 24 (09) 578-580
    CrossrefPubMedSearch in Google Scholar
  • 8 Bladen CL, Thompson R, Jackson JM. et al. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol 2014; 261 (01) 152-163
    CrossrefPubMedSearch in Google Scholar
  • 9 Wenninger S, Stahl K, Montagnese F, Schoser B. Utility and Results from a Patient-Reported Online Survey in Myotonic Dystrophies Types 1 and 2. Eur Neurol 2020; 83 (05) 523-533
    CrossrefPubMedSearch in Google Scholar
  • 10 Ruiter AM, Strijbos E, de Meel RHP. et al. Accuracy of patient-reported data for an online patient registry of autoimmune myasthenia gravis and Lambert-Eaton myasthenic syndrome. Neuromuscul Disord 2021; 31 (07) 622-632
    CrossrefPubMedSearch in Google Scholar
  • 11 Sanson B, Stalens C, Guien C. et al; French FSHD registry collaboration group. Convergence of patient- and physician-reported outcomes in the French National Registry of Facioscapulohumeral Dystrophy. Orphanet J Rare Dis 2022; 17 (01) 96
    CrossrefPubMedSearch in Google Scholar
  • 12 Verhaart IEC, Robertson A, Leary R. et al. A multi-source approach to determine SMA incidence and research ready population. J Neurol 2017; 264 (07) 1465-1473
    CrossrefPubMedSearch in Google Scholar
  • 13 Coratti G, Ricci M, Capasso A. et al; ITASMAC working group. Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey. Neurology 2023; 100 (11) 522-528
    CrossrefPubMedSearch in Google Scholar
  • 14 Parsons DW, McAndrew PE, Iannaccone ST, Mendell JR, Burghes AH, Prior TW. Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number. Am J Hum Genet 1998; 63 (06) 1712-1723
    CrossrefPubMedSearch in Google Scholar
  • 15 Mendonça RH, Matsui Jr C, Polido GJ. et al. Intragenic variants in the SMN1 gene determine the clinical phenotype in 5q spinal muscular atrophy. Neurol Genet 2020; 6 (05) e505
    CrossrefPubMedSearch in Google Scholar
  • 16 Lin CW, Kalb SJ, Yeh WS. Delay in Diagnosis of Spinal Muscular Atrophy: A Systematic Literature Review. Pediatr Neurol 2015; 53 (04) 293-300
    CrossrefPubMedSearch in Google Scholar
  • 17 Pera MC, Coratti G, Berti B. et al. Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?. PLoS One 2020; 15 (03) e0230677
    CrossrefPubMedSearch in Google Scholar
  • 18 Mansouri V, Heidari M, Bemanalizadeh M. et al. The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy. J Neuromuscul Dis 2023; 10 (02) 211-225
    CrossrefPubMedSearch in Google Scholar
  • 19 Bueno KC, Gouvea SP, Genari AB. et al. Detection of spinal muscular atrophy carriers in a sample of the Brazilian population. Neuroepidemiology 2011; 36 (02) 105-108
    CrossrefPubMedSearch in Google Scholar
  • 20 Mercuri E, Finkel RS, Muntoni F. et al; SMA Care Group. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord 2018; 28 (02) 103-115
    CrossrefPubMedSearch in Google Scholar
  • 21 Finkel RS, Mercuri E, Meyer OH. et al; SMA Care group. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 2018; 28 (03) 197-207
    CrossrefPubMedSearch in Google Scholar
  • 22 Slayter J, Casey L, O'Connell C. Patient Reported Outcome Measures in Adult Spinal Muscular Atrophy: A Scoping Review and Graphical Visualization of the Evidence. J Neuromuscul Dis 2023; 10 (02) 239-250
    CrossrefPubMedSearch in Google Scholar
  • 23 Mongiovi P, Dilek N, Garland C. et al. Patient Reported Impact of Symptoms in Spinal Muscular Atrophy (PRISM-SMA). Neurology 2018; 91 (13) e1206-e1214
    CrossrefPubMedSearch in Google Scholar
  • 24 Kolb SJ, Coffey CS, Yankey JW. et al; NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol 2017; 82 (06) 883-891
    CrossrefPubMedSearch in Google Scholar
  • 25 Lusakowska A, Jedrzejowska M, Kaminska A. et al. Observation of the natural course of type 3 spinal muscular atrophy: data from the polish registry of spinal muscular atrophy. Orphanet J Rare Dis 2021; 16 (01) 150
    CrossrefPubMedSearch in Google Scholar
  • 26 Wadman RI, Wijngaarde CA, Stam M. et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. Eur J Neurol 2018; 25 (03) 512-518
    CrossrefPubMedSearch in Google Scholar
  • 27 Brasil. Ministério da Saúde. Secretaria de Ciência T e IE. Aprova o Protocolo Clínico e Diretriz Terapêutica da Atrofia Muscular Espinhal 5q tipos 1 e 2. 2022 ; Available from: https://www.gov.br/conitec/pt-br/midias/relatorios/2022/20220201_relatorio_691_pcdt_atrofia_muscular_espinhal_5q_tipo-ieii.pdf Accessed 01 Feb 2023
    Search in Google Scholar
  • 28 Zanoteli E, Araujo APQC, Becker MM. et al. Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy. Arq Neuropsiquiatr 2024; 82 (01) 1-18
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Mendonça RH, Polido GJ, Matsui C. et al. Real-World Data from Nusinersen Treatment for Patients with Later-Onset Spinal Muscular Atrophy: A Single Center Experience. J Neuromuscul Dis 2021; 8 (01) 101-108
    CrossrefPubMedSearch in Google Scholar