Spinal Muscular Atrophy Research Articles

Hereditary sensory autonomic neuropathy type VI in the age of genetic testing

AbstractBackgroundHereditary sensory and autonomic neuropathy type VI (HSAN VI) is a rare recessive genetic disorder caused by mutations in the human dystonin (DST) gene. We report a novel homozygous alternate transcript mutation in the DST gene causing a severe neonatal form of HSAN VI.Patient DescriptionThis baby boy was born with severe hypotonia, respiratory distress, dysmorphic features, and bilateral club feet. Imaging, karyotyping, Prader–Willi assay, spinal muscular atrophy genetic panel and myotonic dystrophy genetic panel were all negative. A comprehensive neuropathy panel detected a homozygous pathogenic variant in the DST gene—alternate transcript NM_015546.4:c.1357G>A (p.Trp4525*). Nerve conduction studies revealed mixed axonal and demyelinating sensorimotor neuropathy, suggesting the possibility of motor involvement in severe forms of this rare condition. The infant ultimately developed sepsis and died from cardiorespiratory arrest. Neuropathological findings of focal and mild spinal nerve axonal degeneration were nonspecific.ConclusionCollective analysis of these patients would help to further characterize the spectrum of disease pathology and could provide insight into the neurophysiology and neuropathology of this rare condition.

Orphan diseases in children: experience in the use of oedematous enteral nutrition

Introduction. Increased protein and energy requirements, as well as intoxication symptoms in patients with malignant neoplasms (MN), spinal muscular atrophy (SMA) and cystic fibrosis (CF) determine the need to use specialized protein detoxification nutrition in their diet.Aim. To evaluate the tolerability and clinical efficacy of the domestic specialized food product of dietary therapeutic and dietary preventive nutrition Protein detoxification cocktail NUTRIO (liquid mixture) in children with orphan diseases, over 2 years old. Materials and methods. We observed 18 children with rare diseases, aged from 2 years 11 months to 16 years. 6 children had a confirmed diagnosis of MN, 10 – SMA, 2 – CF. All children received the NUTRIO Detox Protein Cocktail twice a day: children aged 3 to 7 years old – ½ serving (100 ml), and aged 8 to 16 years – 1 serving (200 ml). The observation period was 1 month.Results. It was found that all patients (100% of patients) highly rated the taste of the product. There were no refusals from the product. No allergic, dyspeptic or other side effects were noted during the observation period. All patients showed positive dynamics of nutritional status, an increase in the level of total protein and albumin in the blood, a decrease in markers of intoxication and inflammation, an improvement in the quality of life, increased endurance, physical activity and an improvement in the psycho-emotional background.Discussion. The results we obtained correlate well with the authors’ data on the clinical efficacy, safety and significant economic benefits of using this diet.Conclusions. The use of the domestic specialized food product of dietary therapeutic and dietary preventive nutrition Protein detoxification cocktail NUTRIO in diet therapy of children with malignant neoplasms, SMA and CF is effective for correcting their nutritional status and improving the quality of life.

Central neurodegeneration in Kennedy’s disease accompanies peripheral motor dysfunction

Spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R2 = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R2 = 0.59, p < 0.01), motor (R2 = 0.63, p < 0.01), and somatosensory (R2 = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.

Nusinersen Improves Motor Function in Type 2 and 3 Spinal Muscular Atrophy Patients across Time.

Spinal muscular atrophy (SMA) is a genetic disorder primarily caused by mutations in the SMN1 gene, leading to motor neuron degeneration and muscle atrophy, affecting multiple organ systems. Nusinersen treatment targets gene expression and is expected to enhance the motor function of voluntary muscles in the limbs and trunk. Motor skills can be assessed through specific scales like the Revised Upper Limb Module Scale (RULM) and Hammersmith Functional Motor Scale Expanded (HFMSE). This study aims to evaluate the influence of nusinersen on the motor skills of patients with SMA Type 2 and 3 using real-world data collected over 54 months. A prospective longitudinal study was conducted on 37 SMA patients treated with nusinersen, analyzing data with R statistical software. The outcomes revealed significant improvements in motor functions, particularly in SMA Type 3 patients with higher RULM and HFSME scores. Additionally, GEE analysis identified time, type, age, and exon deletions as essential predictors of motor score improvements. The extended observation period is both a major strength and a limitation of this research, as the dropout rates could present challenges in interpretation. Variability in responses, influenced by genetic background, SMA type, and onset age, highlights the need for personalized treatment approaches.

Hematopoietic stem cell transplantation leads to biochemical and functional correction in two mouse models of acid ceramidase deficiency

Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) are ultra-rare lysosomal storage disorders caused by deficient acid ceramidase (ACDase) activity. Although both conditions are caused by mutations in the ASAH1 gene, clinical presentations differ considerably. FD patients usually die in childhood while SMA-PME patients can live until adulthood. There is no treatment for FD or SMA-PME. Hematopoietic stem cell transplantation (HSCT) and gene therapy strategies for the treatment of ACDase deficiency are being investigated. We have previously generated and characterized mouse models of both FD and SMA-PME that recapitulate the symptoms described in patients. Here, we show that HSCT improves lifespan, behavior, hematopoietic system anomalies, plasma cytokine levels, and significantly reduces histiocytic infiltration and ceramide accumulation throughout the tissues investigated, including the CNS, in both models of ACDase deficient mice. HSCT was also successful in preventing lesion development and significant demyelination of the spinal cord seen in SMA-PME mice. Importantly, we note that only early and generally pre-symptomatic treatment was effective and kidney impairment was not improved in either model.

Heterozygous knockout of Synaptotagmin13 phenocopies ALS features and TP53 activation in human motor neurons

Spinal motor neurons (MNs) represent a highly vulnerable cellular population, which is affected in fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we show that the heterozygous loss of SYT13 is sufficient to trigger a neurodegenerative phenotype resembling those observed in ALS and SMA. SYT13+/− hiPSC-derived MNs displayed a progressive manifestation of typical neurodegenerative hallmarks such as loss of synaptic contacts and accumulation of aberrant aggregates. Moreover, analysis of the SYT13+/− transcriptome revealed a significant impairment in biological mechanisms involved in motoneuron specification and spinal cord differentiation. This transcriptional portrait also strikingly correlated with ALS signatures, displaying a significant convergence toward the expression of pro-apoptotic and pro-inflammatory genes, which are controlled by the transcription factor TP53. Our data show for the first time that the heterozygous loss of a single member of the synaptotagmin family, SYT13, is sufficient to trigger a series of abnormal alterations leading to MN sufferance, thus revealing novel insights into the selective vulnerability of this cell population.

Emphasis on the importance of comprehensive clinical and genetic analysis - spinal muscular atrophy combined with phenylketonuria: A case report.

Both spinal muscular atrophy (SMA) and Phenylketonuria (PKU) are caused by biallelic pathogenic mutations. However, there has been no report on case who suffering from both diseases simultaneously. SMA mainly affects the motor function while PKU may have an impact on both the intelligence and motor function. But if only 1 disease is treated while neglecting the other, the treatment effect will be compromised. Here, for the first time, we report a case from China diagnosed with both these diseases and treated properly. A boy was admitted to the Children's Hospital Affiliated to Shandong University (Jinan, China) due to "limb weakness for 19 months" when he was 22 months old. Considering that the child's motor function development is delayed, we made a comprehensive examinations including inherited metabolic diseases and found a significantly increase of phenylalanine concentration in the blood which indicating PKU. Combined with his typical clinical manifestations of SMA, target capture sequencing followed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) technologies were used for genetic confirmation. SMA and PKU was confirmed. The child was treated with risdiplam and low phenylalanine formula immediately when he was diagnosed with both SMA and PKU. The child showed remarkable improvement in motor function and significant decrease of blood phenylalanine concentration after treatment. To our knowledge, this is the first reported case of SMA combined with PKU. This case expands our understanding of diagnosis for synchronous SMA and PKU and highlights the importance of comprehensive examinations and the utilizing of various genetic testing methods to make an accurate diagnosis of genetic diseases, which may help avoiding the progressive damage caused by certain genetic disease with insidious clinical symptoms.

Nusinersen in the treatment of 4 children with presymptomatic spinal muscular atrophy

Nusinersen in the treatment of 4 children with presymptomatic spinal muscular atrophy

Complex SMN Hybrids Detected in a Cohort of 31 Patients With Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder caused by the loss or presence of point pathogenic variants in the SMN1 gene. The main positive modifier of the SMA phenotype is the number of copies of the SMN2 gene, a paralog of SMN1, which only produces around 10%-15% of functional SMN protein. The SMN2 copy number is inversely correlated with phenotype severity; however, discrepancies between the SMA type and the SMN2 copy number have been reported. The presence of SMN2-SMN1 hybrids has been proposed as a possible modifier of SMA disease. We studied 31 patients with SMA, followed at a single center and molecularly diagnosed by Multiplex Ligand-Dependent Probe Amplification (MLPA), with a specific next-generation sequencing protocol to investigate their SMN2 genes in depth. Hybrid characterization also included bioinformatics haplotype phasing and specific PCRs to resolve each SMN2-SMN1 hybrid structure. We detected SMN2-SMN1 hybrid genes in 45.2% of the patients (14/31), the highest rate reported to date. This represents a total of 25 hybrid alleles, with 9 different structures, of which only 4 are detectable by MLPA. Of particular interest were 2 patients who presented 4 SMN2-SMN1 hybrid copies each and no pure SMN2 copies, an event reported here for the first time. No clear trend between the presence of hybrids and a milder phenotype was observed, although 5 of the patients with hybrid copies showed a better-than-expected phenotype. The higher hybrid detection rate in our cohort may be due to both the methodology applied, which allows an in-depth characterization of the SMN genes and the ethnicity of the patients, mainly of African origin. Although hybrid genes have been proposed to be beneficial for patients with SMA, our work revealed great complexity and variability between hybrid structures; therefore, each hybrid structure should be studied independently to determine its contribution to the SMA phenotype. Large-scale studies are needed to gain a better understanding of the function and implications of SMN2-SMN1 hybrid copies, improving genotype-phenotype correlations and prediction of the evolution of patients with SMA.

The Impact of Nusinersen and Risdiplam on Motor Function for Spinal Muscular Atrophy Type 2 and 3: A Meta-Analysis.

Spinal muscular atrophy (SMA) is a prevalent paediatric neuromuscular disorder characterised by muscle weakness and atrophy resulting from degeneration of spinal cord anterior horn α motor neurons. Gene therapy formulations exhibit varying benefits and limitations, driving the need for patient-friendly treatment options tailored to specific populations. The objective of this meta-analysis was to assess the effectiveness of gene therapy for motor function in children with SMA. The analysis encompassed a total of 719 participants from six randomised controlled trials (RCTs) conducted between 2017 and 2023. Among the studies, one demonstrated a significant and large standardised effect size (Cohen's d) favouring nusinersen in terms of Hammersmith Functional Motor Scale - Expanded (HFMSE) (d = 0.97) and revised upper limb module (RULM) (d = 0.96). Additionally, another study showed a moderate standardised effect size (Cohen's d) in favour of nusinersen concerning Hammersmith Infant Neurological Examination-Section 2 (HINE-2) (d = 0.48). However, it is important to note that further research with a longer duration of observation is required to strengthen the evidence. Key Words: Spinal muscular atrophy, Nusinersen, Risdiplam, Motor function, Cohen's d.

Spinal muscular atrophy in an upper-middle-income nation before the advent of reimbursed disease-modifying therapies

ObjectiveTo elucidate the clinical characteristics and standard of care (SoC) of spinal muscular atrophy (SMA) patients in Thailand, focusing on primary endpoints: age at death and a composite of death...

Rehabilitation Strategies for Patients With Spinal Muscular Atrophy in the Era of Disease-Modifying Therapy.

The impact of disease-modifying therapy ranges from cure to no impact with a wide range of intermediates. In cases where the intermediate group reaches a plateau after the acquisition of some muscle strength, it is necessary to set a functional level appropriate for increased motor power and establish a long-term exercise plan to maintain it. As the disease status stabilizes and the life span increases, early nonsurgical interventions are required, such as using a standing frame to prevent joint contracture, applying a spinal brace at the early stage of scoliosis, and maintaining sitting postures that exaggerate lumbar lordosis. In cases where scoliosis and hip displacement occur and progress even after conservative managements are implemented, early referral to surgery should be considered. Oromotor activity and swallowing function are influenced not only by the effects of disease-modifying drugs, but also by post-birth experience and training. Therefore, although the feeding tube cannot be removed, it is necessary to make efforts to simulate the infant feeding development while maintaining partial oral feeding. Since the application period of non-invasive ventilators has increased, it has become more important to prevent long-term complications such as facial abrasion, skin allergy, orthodontic deformities, and maxillary flattening caused by the interface. Dual ventilator mode or interface can also be utilized.

Complex neural tube and skeletal malformations, resembling Chiari malformations, in two calves.

Two 1-day-old full-term female calves from different farms located in the Brazilian state of Rio Grande do Sul were unable to stand due to paresis of the pelvic limbs. Both calves had spina bifida on the spinal lumbar segment and were submitted to euthanasia due to poor prognosis. Postmortem examination revealed cerebellar herniation, caudal displacement of the brainstem, rostral deviation of the cranial nerves, caudal extension of occipital lobes, absence of dorsal lamina of lumbar vertebrae with exposed spinal cord, myelodysplasia, kyphosis, segmental spinal agenesis, renal fusion, muscular atrophy, and arthrogryposis. Histology highlighted myelodysplasia (syringomyelia and diplomyelia) and muscular atrophy. The reverse transcription-polymerase chain reactions for ruminant pestivirus were negative. Based on these lesions, the diagnosis of complex neural tube and skeletal malformations was made. A review of previous publications on calves diagnosed with these malformations, originally called Chiari or Arnold-Chiari malformations, revealed a wide range of nervous system and skeletal lesions. These variations amplified the uncertainty regarding whether all cases represent the same disorder and reinforced the importance of reconfiguring the terminology.

Spinal Muscular Atrophy Update in Best Practices: Recommendations for Diagnosis Considerations.

Spinal muscular atrophy (SMA) is an autosomal recessive progressive neurodegenerative primary motor neuron disorder caused by biallelic variants of the survival motor neuron 1 (SMN1) gene. The most recent SMA best practice recommendations were published in 2018 shortly after the approval of the first SMN-enhancing treatment. The availability of disease-modifying therapies for 5q SMA and implementation of SMA newborn screening (NBS) has led to urgency to update the SMA best practice recommendations for diagnosis and to reevaluate the current classification of SMA. In addition, the availability of disease-modifying therapies has opened the door to explore improved diagnosis of adult-onset SMA. A systematic literature review was conducted on SMA NBS. An SMA working group of American and European health care providers developed recommendations through a modified Delphi technique with serial surveys and virtual meeting feedback on SMA diagnosis to fill information gaps for topics with limited evidence. A community working group of an individual with SMA and caregivers provided insight and perspective on SMA diagnosis and support through a virtual meeting to guide recommendations. The health care provider working group achieved consensus that SMA NBS is essential to include in the updated best practice for SMA diagnosis (100%). Recommendations for the following are described: characterizing NBS-identified infants before treatment; minimum recommendations for starting or offering SMA NBS in a state or country; recommendations for activities and services to be provided by an SMA specialty care center accepting SMA NBS referrals; and recommendations for partnership with individuals with SMA and caregivers to support NBS-identified infants and their caregivers. Limited data are available to advance efficient diagnosis of adult-onset SMA. Updating best practice recommendations for SMA diagnosis to include SMA NBS implementation is essential to advancing care for individuals with SMA. In addition to testing, processes for the efficient management of positive newborn screen with access to knowledgeable and skilled health care providers and access to treatment options is critical to successful early diagnosis. Additional evidence is required to improve adult-onset SMA diagnosis.

The molecular mechanisms that underlie IGHMBP2-related diseases.

Immunoglobulin Mu-binding protein 2 (IGHMBP2) pathogenic variants result in the fatal, neurodegenerative disease spinal muscular atrophy with respiratory distress type 1 (SMARD1) and the milder, Charcot-Marie-Tooth (CMT) type 2S (CMT2S) neuropathy. More than 20 years after the link between IGHMBP2 and SMARD1 was revealed, and 10 years after the discovery of the association between IGHMBP2 and CMT2S, the pathogenic mechanism of these diseases is still not well defined. The discovery that IGHMBP2 functions as an RNA/DNA helicase was an important step, but it did not reveal the pathogenic mechanism. Helicases are enzymes that use ATP hydrolysis to catalyse the separation of nucleic acid strands. They are involved in numerous cellular processes, including DNA repair and transcription; RNA splicing, transport, editing and degradation; ribosome biogenesis; translation; telomere maintenance; and homologous recombination. IGHMBP2 appears to be a multifunctional factor involved in several cellular processes that regulate gene expression. It is difficult to determine which processes, when dysregulated, lead to pathology. Here, we summarise our current knowledge of the clinical presentation of IGHMBP2-related diseases. We also overview the available models, including yeast, mice and cells, which are used to study the function of IGHMBP2 and the pathogenesis of the related diseases. Further, we discuss the structure of the IGHMBP2 protein and its postulated roles in cellular functioning. Finally, we present potential anomalies that may result in the neurodegeneration observed in IGHMBP2-related disease and highlight the most prominent ones.

Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin.

The most prevalent rare genetic disease affecting young individuals is spinal muscular atrophy (SMA), which is caused by a loss-of-function mutation in the telomeric gene survival motor neuron (SMN) 1. The high heterogeneity of the SMA pathophysiology is determined by the number of copies of SMN2, a separate centromeric gene that can transcribe for the same protein, although it is expressed at a slower rate. SMA affects motor neurons. However, a variety of different tissues and organs may also be affected depending on the severity of the condition. Novel pharmacological treatments, such as Spinraza, Onasemnogene abeparvovec-xioi, and Evrysdi, are considered to be disease modifiers because their use can change the phenotypes of the patients. Since oxidative stress has been reported in SMA-affected cells, we studied the impact of antioxidant therapy on neural stem cells (NSCs) that have the potential to differentiate into motor neurons. Antioxidants can act through various pathways; for example, some of them exert their function through nuclear factor (erythroid-derived 2)-like 2 (NRF2). We found that curcumin is able to induce positive effects in healthy and SMA-affected NSCs by activating the nuclear translocation of NRF2, which may use a different mechanism than canonical redox regulation through the antioxidant-response elements and the production of antioxidant molecules.

The prevalence of SMN gene deletion/duplication in spinal muscular atrophy families referred to neuro-genetic centers of Mashhad, Iran

BackgroundSpinal muscular atrophy (SMA) is a group of motor neuron diseases. In 95% of SMA patients, the telomeric copy of the SMN gene (SMN1) is homozygously deleted. Due to the autosomal recessive pattern of SMA inheritance, individuals with a family history of SMA are at risk of being carriers. A total of 622 individuals from SMA families, including parents, siblings, and first, second, and third-degree relatives, were recruited to the neuro-genetic clinic of Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. SMA cases and suspected carriers were referred to the genetic laboratory. Pregnant women underwent amniocentesis and chorionic villi sampling at 12–14 gestational weeks. RFLP-PCR and real-time PCR were performed for symptomatic and asymptomatic individuals (possible carriers), respectively. RFLP and real-time PCR were performed for amniotic fluid and chorionic villi samples.ResultsThe study enrolled 622 subjects from SMA-affected families, including 159 fetuses and 463 non-fetuses. Two samples were missing. A total of 268 individuals (43.2%) were healthy (wild type), 187 individuals (30.1%) were heterozygous for exon deletion of SMN1, and 143 individuals (23%) were homozygous for exon deletion of SMN1. Four individuals (0.6%) showed three copies of the SMN1 gene.ConclusionThe frequency of carriers with two SMN1 copies on a single chromosome (cis) was estimated at 2.9% (18/622), and the total rate of carriers was approximately 21.8%. Considering the high rate of SMA carriers in this study, genetic counseling and definitive prenatal diagnosis are of utmost importance for reducing the psychosocial burden of the SMA disease among Iranian families.

Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges.

Spinal muscular atrophy (SMA) is a severe genetic disorder characterized by the loss of motor neurons, leading to progressive muscle weakness, loss of mobility, and respiratory complications. In its most severe forms, SMA can result in death within the first two years of life if untreated. The condition arises from mutations in the SMN1 (survival of motor neuron 1) gene, causing a deficiency in the survival motor neuron (SMN) protein. Humans possess a near-identical gene, SMN2, which modifies disease severity and is a primary target for therapies. Recent therapeutic advancements include antisense oligonucleotides (ASOs), small molecules targeting SMN2, and virus-mediated gene replacement therapy delivering a functional copy of SMN1. Additionally, recognizing SMA's broader phenotype involving multiple organs has led to the development of SMN-independent therapies. Evidence now indicates that SMA affects multiple organ systems, suggesting the need for SMN-independent treatments along with SMN-targeting therapies. No single therapy can cure SMA; thus, combination therapies may be essential for comprehensive treatment. This review addresses the SMA etiology, the role of SMN, and provides an overview of the rapidly evolving therapeutic landscape, highlighting current achievements and future directions.

SMN1 c.5C>G (p.Ala2Gly) missense variant, a challenging molecular SMA diagnosis associated with mild disease, preserves SMN nuclear gems in patient-specific fibroblasts.

Spinal muscular atrophy (SMA) is caused by homozygous loss of the SMN1 gene with SMN2 gene copy number correlating with disease severity. Rarely SMA is caused by a deletion on one allele and a pathogenic variant on the other. The pathogenic missense variant c.5C>G (p.Ala2Gly) correlates with a mild disease phenotype that does not correlate with SMN2 copy number. In a mouse model the c.5C>G transgene produces SMN that is thought to form partially functional SMN complexes, but levels in humans have not yet been investigated. We identified two patients with mild SMA caused by a heterozygous deletion of SMN1 and the heterozygous variant, c.5C>G. Molecular findings were confirmed with deletion/duplication analysis and Sanger sequencing. Skin fibroblasts were collected and cultured, and SMN expression was analyzed using immunofluorescence. Two patients with slowly progressing mild weakness were confirmed to have heterozygous pathogenic missense variant c.5C>G and a heterozygous deletion of SMN1. Their clinical presentation revealed much milder disease progression than patients with matched SMN2 copy number. Analysis of the patients' fibroblasts revealed much higher numbers of SMN nuclear complexes than a patient with a homozygous SMN1 deletion and matched SMN2 copy number. These case reports reinforce that the rare c.5C>G variant causes mild disease. Furthermore, the analysis of SMA nuclear gems in patient samples supports the theory that the p.Ala2Gly SMN can form partially functional SMN complexes that may carry out essential cellular functions and result in mild disease.

The Spectrum of Childhood-Onset Lower Motor Neuron Disease of Spinal Muscular Atrophy Phenotype Associated with Survival Motor Neuron-2 Gene Deletion

AbstractPediatric lower motor neuron disease is clinically and genetically heterogeneous. We characterized disease progression among children with the spinal muscular atrophy (SMA) phenotype having 2:0 (group A) and 2:1 (group B) of the survival motor neuron 1/2 (SMN1:SMN2) genotype over 1 year. We included children aged 0 to 12 with the SMA phenotype between January 2018 and December 2021. Their demographic, clinical (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP-INTEND] scores), electrophysiological, radiological, and genetic data were collected from past medical records. The sequential CHOP-INTEND scores and the compound muscle action potential (CMAP) amplitudes were compared using an analysis of covariance test, controlling for age and sex. A linear regression was run to determine the association between the ages of the patients and the CHOP-INTEND scores. Among nine children in group A and six in group B, the decline of the mean (standard deviation) CHOP-INTEND score from the initial value to the 12th-month follow-up value was significant only in group A. CHOP-INTEND scores did not significantly differ between the two groups at the first admission but were significantly lower in group A at the subsequent visits. Group A patients had significantly lower CMAP amplitudes than patients in group B. There was a moderate, negative association between the age of patients and the CHOP-INTEND scores in group A. Group A patients had a significantly higher age-dependent decline in CHOP-INTEND scores and CMAP values than group B, although their age and the severity of weakness did not significantly differ at presentation.