SYNE1 deficiency is an autosomal recessive disorder with a broad phenotypic spectrum, most commonly presenting as adult-onset cerebellar ataxia with or without motor neuron dysfunction. We aimed to expand this spectrum by describing the clinical and genetic findings in 2 unrelated families with early-onset motor neuron disease and virtually no cerebellar signs over time. We performed detailed clinical, neurophysiologic, and genetic studies of 2 unrelated families with juvenile amyotrophic lateral sclerosis (ALS) and biallelic variants in SYNE1. The phenotypes of both families showed onset of symptoms in childhood or adolescence, with signs of upper and lower motor neuron dysfunction in multiple territories suggestive of juvenile ALS. Patients developed progressive muscle weakness, eventually leading to respiratory distress and bulbar signs. Whole-exome sequencing identified SYNE1 biallelic truncating variants in both families: a homozygous nonsense variant, c.23131C>T (p.Gln7711*), in Family 1, and a novel homozygous splice-site variant, c.17851-1G>A, in Family 2. Notably, mild or no cerebellar manifestations were observed during the follow-up. This report highlights a novel phenotype of SYNE1 deficiency characterized by early-onset motor neuron disease and virtually no cerebellar manifestations, broadening the phenotypic spectrum of this complex neurodegenerative disease. These findings support investigating SYNE1 variants in juvenile ALS and including SYNE1 in motor neuron disease gene panels.

Spinal Muscular Atrophy (SMA) is a rare autosomal recessive genetic disorder characterized by degeneration of motor neurons in the spinal cord, resulting in progressive limb muscle weakness, atrophy, and severe scoliosis. Clinically, it is divided into four types according to age at onset and severity. There are few cases reported in the literature presently, especially type II cases, and no expert consensus or guideline for the anesthetic management of spinal muscular atrophy (SMA) with scoliosis. This article discusses anesthesia management and intraoperative considerations for this patient, as well as how to help the patient reduce perioperative complications. To the best of our knowledge, this is the first case of continuous thoracolumbar dorsal ramus nerve block for pain relief after scoliosis surgery in a patient with spinal muscular atrophy type II. We described a 17-year-old patient with spinal muscular atrophy scoliosis (SMA type II) who underwent posterior scoliosis osteotomy and orthopedic laminectomy and fusion under general anesthesia without muscle relaxants, A series of optimized anesthesia management measures were successfully implemented, aiming to reduce perioperative related complications. After the operation, continuous thoracolumbar dorsal ramus nerve block was carried out and achieved a good analgesic effect. The patient was discharged 33 days after hospitalization. It is indicated that anesthesia management for patients with SMA is a real challenge for all anesthesia providers. For patients with SMA undergoing scoliosis surgery, total intravenous anesthesia without muscle relaxants and continuous thoracolumbar dorsal ramus nerve block after surgery have been proven to be both efficient and safe. It is also crucial to implement preoperative multidisciplinary consultation, lung-protective ventilation strategy, appropriate anesthetic drugs, reasonable blood transfusion scheme, as well as strengthened postoperative monitoring and multimodal analgesia.

Spinal muscular atrophy is a severe, progressive autosomal recessive neuromuscular disorder associated with neuromuscular scoliosis. When bracing is not sufficient to control the deformity, early spinal surgery is required. To the best of our knowledge, no work in the literature have assessed modifications in spinal and thigh muscles of subjects with type 2 spinal muscular atrophy (SMA2) following spinal surgery. This study aimed to better understand modifications in the spinal and thigh muscles of subjects with SMA2 and early onset scoliosis, before and after minimally invasive fusionless surgery. 20 SMA2 patients with confirmed scoliosis on bi-planar low-dose X-ray were included: 10 preoperative and 10 postoperative patients with a minimal follow-up of 5 years after surgery. The surgery consisted of a bilateral sliding rod construct extended from T1 to the sacrum, through a minimally invasive approach. All subjects had fat/water separation muscle magnetic resonance imaging from the spine to the thigh. The percentage of fat degeneration was compared before and after surgery. A quality-of-life survey was performed. Fat infiltration was diffuse and symmetric in both groups of patients, and on average six times more compared to control subjects previously published at thigh level. Adductors, sartorius, and gracilis were less affected with respectively, 51%, 56%, and 57% of fat fraction before surgery. Comparing the preoperative and postoperative groups, fat infiltration was higher in sartorius and multifidus after surgery (p < 0.05). No significant difference was found for the other muscles studied. These results did not affect quality of life. This is the first study to compare fat infiltration of spinal and thigh muscles of SMA2 patients before and after minimally invasive surgery. Our results demonstrate that muscles were globally preserved apart from multifidus and sartorius which were more affected.

Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. We reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed. Delayed motor milestones were defined as being unable to hold the head up by four months, sitting unassisted by nine months, and walking independently by 17 months. If there were no delayed motor milestones, age at disease onset was determined by leg stiffness, frequent falls, or unsteady gait. Genetic testing was performed based on delayed motor milestones, progressive leg spasticity, and gait difficulty. The variant classification was determined based on the American College of Medical Genetics standard guidelines for variant interpretation. Variants of uncertain significance (VUS) were considered disease-associated when clinical findings were consistent with the previously described disease phenotypes for pathogenic variants. In addition, in the absence of another pathogenic, likely pathogenic, or VUS variant that could explain the phenotype of our cases, we concluded that the disease is associated with VUS in the HSP-causing gene. Segregation analysis was also performed on the parents of some patients to demonstrate the inheritance model. There were a total of 18 patients from 17 families. The median age of symptom onset was 18 months (2 to 84 months). The mean delay between symptom onset and genetic diagnosis was 5.8 years (5 months to 17 years). All patients had gait difficulty caused by progressive leg spasticity and weakness. Independent walking was not achieved at 17 months for 67% of patients (n = 12). In our cohort, there were two subjects each with SPG11, SPG46, and SPG 50 followed by single subject each with SPG3A, SPG4, SPG7, SPG8, SPG30, SPG35, SPG43, SPG44, SPG57, SPG62, infantile-onset ascending spastic paralysis (IAHSP), and spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Eight novel variants in nine patients were described. Two affected siblings had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44), ERLIN1 (SPG62), ALS2 (IAHSP), and HACE1 (SPPRS). Among the novel variants, the variant in the SPG11 was pathogenic and the variants in the KIF1A, GJC2, and HACE1 were likely pathogenic. The variants in the GBA2, ALS2, ERLIN1, and WASHC5 were classified as VUS. There was a significant delay between symptom onset and genetic diagnosis of HSP. An early diagnosis may be possible by examining patients with delayed motor milestones, progressive spasticity, gait difficulties, and neuromuscular weakness in the context of HSP. Eight novel variants in nine patients were described, clinically similar to the previously described disease phenotype associated with pathogenic variants. This study contributes to expanding the genetic spectrum of some rare subtypes of HSP.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease characterized by the loss of motor neurons in the spinal cord and brainstem, leading to muscle atrophy and weakness. To understand the diagnostic process of Korean patients with SMA, we analyzed their clinical characteristics and challenges. We conducted a retrospective study of 38 patients with SMA (9 type II and 29 type III) between January 2000 and September 2023. Clinical, laboratory, and genetic data were reviewed. The median ages at symptom onset and diagnosis were 3.0 years [interquartile range (IQR): 1.0-7.3 years] and 25.0 years (IQR: 10.5-37.3 years), respectively. The median diagnostic delay was 19.6 years (IQR: 6.4-31.0 years). A significantly longer delay was observed in SMA type III patients (median: 21.0 years, IQR: 11.0-31.0 years) compared to SMA type II patients (median: 3.0 years, IQR: 0.9-21.0 years) (p=0.021). No significant difference was observed in the number of clinic visits before diagnosis between patients with SMA type II (median: 2.0, IQR: 1.0-4.5) and those with type III (median: 2.0, IQR: 2.0-6.0, p=0.282). The number of clinic visits before diagnosis showed no significant association with the age at symptom onset and diagnosis (p=0.998 and 0.291, respectively). Our investigation is the first examination of the diagnostic journey of Korean patients with SMA. As treatments for SMA progress, the significance of an accurate diagnosis has increased, highlighting the importance of reviewing the diagnostic advancements made thus far.