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The emerging spectrum of neurodevelopmental comorbidities in early-onset Spinal Muscular Atrophy

2023; Elsevier BV; Volume: 48; Linguagem: Inglês

10.1016/j.ejpn.2023.11.006

1532-2130

Giovanni Baranello, Susana Quijano Roy, Laurent Servais, Francina Munell, Mireia Alvarez Molinero, Daniel Natera‐de Benito, A. Nascimento, David Gómez‐Andrés, Laura Costa-Comellas, Jessica Exposito, Eduardo F. Tizzano, Inge Cuppen, Ludo van der Pol, Alberto Alemán, Hanns Lochmüller, Hugh J. McMillan, Janbernd Kirschner, C. Müller, Maryam Oskoui, Riccardo Masson, Claudio Bruno, Hernán Gonorazky, Carolina Tesi Rocha, Amanda Yaworski, Edmar Zanoteli, Rodrigo Holanda Mendonça, Adele D’Amico, Francesca Cumbo, Michele Tosi, Marika Pane, Eugenio Mercuri, Flávia Nardes, A. Prufer, Brenda Klemm Arci, Samuel Ignacio Pascual Pascual, Aviva Fattal‐Valevski, Liesbeth De Waele, Nicolas Deconinck, Michelle A. Farrar, Jana Haberlová, Marta Gómez‐García de la Banda, Anne‐Marie Childs, Cristina Martos, Elizabeth Wraige, Vasantha Gowda, Marjorie Illingworth, Min Ong, Anirban Majundar, Imelda Hughes, Krupa Torne, Tracey Willis, Sithara Ramdas, Christian de Goede, Yasemin Erbaş, Chiara Brusa, Mariacristina Scoto, Francesco Muntoni,

RNA Research and Splicing

Spinal muscular atrophy (SMA) type 1, or early-onset SMA, is the most common and severe form of SMA 5q, an autosomal recessive neuromuscular disorder caused by bi-allelic deletions or pathogenic variants in the SMN1 gene. The resulting deficiency of the survival motor neuron (SMN) protein leads to degeneration of motor neurons in brainstem and spinal cord [ [1] Wirth B. Karakaya M. Kye M.J. Mendoza-Ferreira N. Twenty-five years of spinal muscular atrophy research: from phenotype to genotype to therapy, and what comes next. Annu. Rev. Genom. Hum. Genet. 2020; 21: 231-261 Crossref Scopus (104) Google Scholar ]. The median age of death is ∼12 months and most children do not survive into the second year of life if not on supportive care. In the last few years, three approved SMN-enhancing medications have dramatically improved the natural history of the disease, with most treated SMA 1 babies now surviving longer and a proportion achieving unprecedented motor milestones like sitting, standing, and walking with support [ [2] Antonaci L. Pera M.C. Mercuri E. New therapies for spinal muscular atrophy: where we stand and what is next. Eur. J. Pediatr. 2023 Apr 17; https://doi.org/10.1007/s00431-023-04883-8 Crossref Scopus (4) Google Scholar ]. However, much less is known about the neurodevelopment of these treated children. Recent reports on small cohorts of treated SMA 1 children, like that from Tosi et al. [ [3] Tosi M. Cumbo F. Catteruccia M. et al. Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers. Eur. J. Paediatr. Neurol. 2023 3; 43: 36-43 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ], have shown that most patients who underwent formal testing scored below average on cognitive and communication scales [ [3] Tosi M. Cumbo F. Catteruccia M. et al. Neurocognitive profile of a cohort of SMA type 1 pediatric patients and emotional aspects, resilience and coping strategies of their caregivers. Eur. J. Paediatr. Neurol. 2023 3; 43: 36-43 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar , [4] Ngawa M. Dal Farra F. Marinescu A.D. Servais L. Longitudinal developmental profile of newborns and toddlers treated for spinal muscular atrophy. Ther Adv Neurol Disord. 2023 Feb 20; 1617562864231154335https://doi.org/10.1177/17562864231154335 Crossref Scopus (0) Google Scholar ], although this was in some cases related to low gross motor function scores While the observation of cognitive and communication defects contrasts with previous assumptions that SMA is a pure motor neuronopathy, this is in line with what many clinicians are observing now that most of these children are on treatment and therefore survive longer and can be followed in their overall development.