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Spinal muscular atrophy (SMA) has gained much attention in the last few years because of the approval of the first intrathecal treatment for this neurodegenerative disease. Latin America needs to develop the demographics of SMA, timely access to diagnosis, and appropriate following of the standards of care recommendations for patients. These are essential steps to guide health policies. Methods: This was a descriptive study of a cohort of SMA patients from all over Chile. We analyzed the clinical, motor functional, and social data, as well as the care status of nutritional, respiratory and skeletal conditions. We also measured the SMN2 copy number in this population. Results: We recruited 92 patients: 50 male; 23 SMA type-1, 36 SMA type-2 and 33 SMA type-3. The median age at genetic diagnosis was 5, 24 and 132 months. We evaluated the SMN2 copy number in 57 patients. The SMA type-1 patients were tracheostomized and fed by gastrostomy in a 69.6 % of cases, 65% of SMA type-2 patients received nocturnal noninvasive ventilation, and 37% of the whole cohort underwent scoliosis surgery. Conclusion: Ventilatory care for SMA type-1 is still based mainly on tracheostomy. This Chilean cohort of SMA patients had timely access to genetic diagnosis, ventilatory assistance, nutritional support, and scoliosis surgery. In this series, SMA type-1 is underrepresented, probably due to restrictions in access to early diagnosis and the high and early mortality rate. RESUMÉNLa Atrofia Muscular Espinal (AME) ha concitado mucha atención en los últimos 2 años debido a la aprobación del primer tratamiento intratecal para esta enfermedad neurodegenerativa. América Latina necesita desarrollar la demografía de AME, un acceso oportuno al diagnóstico y un seguimiento apropiado de los pacientes que incorporen los estándares de atención recomendados por expertos. Estos son pasos esenciales para orientar las futuras políticas de salud en esta enfermedad. Métodos: Este es un estudio descriptivo de una cohorte de pacientes con AME de todo el país. Se analizaron los datos clínicos, motores, funcionales, sociales y el estado nutricional, respiratorio y esquelético de los pacientes. También medimos el número de copias del gen SMN2 en esta población. Resultados: se reclutaron 92 pacientes, 50 varones; 23 AME tipo 1, 36 AME tipo 2 y 33 AME tipo 3. La edad media al diagnóstico genético fue de 5, 24 y 132 meses respectivamente. Evaluamos el número de copias de SMN2 en 57 pacientes. Un 69,6% de los pacientes con AME tipo 1 estaban traqueostomízados y gastrostomizados , un 65% de los pacientes con AME tipo 2 usaban ventilación nocturna no invasiva y el 37% de toda la cohorte presentaba una cirugía de escoliosis. Conclusión: Esta cohorte chilena de pacientes con AME tuvo acceso oportuno al diagnóstico genético, asistencia ventilatoria, apoyo nutricional y cirugía de escoliosis, sin embargo, la atención ventilatoria para AME tipo 1 continúa aun basándose principalmente en la traqueostomía. En esta serie, AME tipo 1 está subrepresentada, probablemente debido a...

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We thank Dr Maeda et al for their careful review and for their contribution of an additional case related to our previous report, "Severe Brain Involvement in 5q Spinal Muscular Atrophy Type 0." 1 We would like to reply to some of the comments in their letter.The case they reported showed severe diffuse atrophy, compromising the supra-and infratentorial central nervous system with seizures. This case represents another example of evolutionary brain atrophy that becomes worse with time in patients with type 0 spinal muscular atrophy (SMA), who survive longer through artificial invasive ventilation. Although the 3 cases that we reported did not show evident cerebellar compromise or seizures, there are previous reports of type 0 SMA with cerebellar involvement and seizures 2 that we commented on in our paper. 1 Maeda et al ascribe the extreme severity of their patient to the presence of 1 SMN2 copy and the absence of the NAIP gene.In addition to the SMN1 gene, 2 other genes located in the 5q13.2 region, NAIP (neuronal apoptosis inhibitory protein, currently BIRC1) and SERF1A (small EDRK-rich factor 1A), have been postulated as possible modifier genes because they are deleted in approximately one-half the patients with severe SMA. 3 However, the roles of these genes have not been unequivocally established, and there is a consensus that the association of these genes with the phenotype may be the result of large-scale rearrangements causing deletion of multiple genes (including the SMNs and other adjacent genes), as previously described by other groups. 4 Thus, true deletions of SMN1 or null alleles are usually associated with the deletion of surrounding genes. NAIP mutations were not specifically studied in our patients. However, 1 of them, who also developed distal necrosis (Patient 3), had 1 allele with the presence of SMN1 and a point pathogenic variant in exon 6, suggesting the presence of surrounding genes, including NAIP. Bernal et al 5 reported that 8 patients with 2 SMN2 copies (usually expected to develop severe type I disease) showed better phenotypes because of the presence of the c.859G>C variant in exon 7 of the SMN2 gene (type II sitter or type III walker). These patients also showed homozygous deletion of NAIP, further supporting the hypothesis that the absence of NAIP is not primarily involved in worsening of the SMA phenotype. References1. Mendonça RH, Rocha AJ, Lozano-Arango A, et al. Severe brain involvement in 5q spinal muscular atrophy type 0. Ann Neurol 2019; 86:458-462. 2. Rudnik-Schöneborn S, Forkert R, Hahnen E, et al. Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings. Neuropediatrics 1996;27:8-15. 3. Medrano S, Monges S, Gravina LP, et al. Genotype-phenotype correlation of SMN locus genes in spinal muscular atrophy children from Argentina. Eur J Paediatr Neurol 2016;20:910-917. 4. Wang CH, Carter TA, Das K, et al. Extensive DNA deletion associated with severe disease alleles on spinal muscular atroph...

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Myopathies secondary to collagen VI mutations (COLVI-M) are the most frequent in the northern hemisphere, affecting the adult and pediatric population. There are no data on its prevalence in Latin America. They are characterized by a great clinical variability, from severe phenotypes, such as Ullrich congenital muscular dystrophy (UCMD), to intermediate and mild ones such as Bethlem myopathy (BM). Its onset is also variable and extends from the neonatal period to adulthood. Given the presence of joint hypermobility, the differential diagnosis should be made with various connective tissue diseases. The classical diagnostic algorithm in many patients has been insufficient to guide the genetic study in an adequate way, and from this the muscular magnetic resonance imaging has emerged as a very useful tool for a better diagnostic approach of this and other muscular pathologies. This ob jective of this review is to study the forms of presentation, clinical characteristics, specific diagnostic study, differential diagnosis and management of one of the most frequent hereditary muscular patho logies, with emphasis on the contribution of muscle magnetic resonance imaging.