Spinal muscular atrophy (SMA) is a rare neuromuscular disease, which is characterized by the degeneration of motor neurons, leading to symmetrical muscle weakness and atrophy. Description of two novel SMN1 mutations (patient1: c.683T > A, p.Leu228Ter; patient2: c.347 T > C, p.Ile116 Thr). We reported two patients with SMN1 mutations with the clinical features, and provided a literature review of the previously reported 22 cases. Two SMA patients showed progressive proximal lower limb weakness and milder clinical symptom. In a total of 22 cases, the most commonly observed SMN1 gene alteration was missense mutation (55%), followed by splicing defect (27%), nonsense (9%) and frameshift (9%). We discuss the possible decisive role of these intragenic mutations in the phenotypic results, which enriched the SMN 1 fine mutation database.

Spinal Muscular Atrophy (SMA), a neurodegenerative disorder, extends its impact beyond the nervous system. The central protein implicated in SMA, Survival Motor Neuron (SMN) protein, is ubiquitously expressed and functions in fundamental processes such as alternative splicing, translation, cytoskeletal dynamics and signaling. These processes are relevant for all cellular systems, including cells of the immune system such as macrophages. Macrophages are capable of modulating their splicing, cytoskeleton and expression profile in order to fulfil their role in tissue homeostasis and defense. However, less is known about impairment or dysfunction of macrophages lacking SMN and the subsequent impact on the immune system of SMA patients. We aimed to review the potential overlaps between SMN functions and macrophage mechanisms highlighting the need for future research, as well as the current state of research addressing the role of macrophages in SMA.

Spinal muscular atrophy (SMA) indicates a set of inherited autosomal recessive genetic disorders, where, specifically, the anterior horn cell motor neurons in the brain and spinal cord are affected, leading to a severe form of hypotonia and muscle weakness. The incidence is exceptionally rare, commonly manifesting as slowly progressive muscular weakness and atrophy of lower limbs. As per our existing knowledge, this is the first case of SMA associated with hyperlordosis in a patient. Hyperlordosis is a deformity in spinal curvature characterized by an excessive forward spinal curve in the region of the lower back, forming the characteristic C-shape curvature in the lumbar region, just above the buttocks. Parents brought an 11-year-old male child with complaints of inability to get up from a sitting position along with difficulty in walking for the past six months. Upon physical examination, deep tendon reflexes were absent; there was severe hyperlordosis, proximal limb weakness, and notable hypotonia. In our study, we aim to understand the clinical presentation, impact, and association of hyperlordosis in a child diagnosed with SMA. This case report describes the complaints and successful diagnosis of a patient of survivor motor neuron (SMN) gene-related SMA along with severe hyperlordosis backed by evidences of electrophysiology and neuropathology. However, a complete cure and normal lifestyle are not possible due to the lack of affordable and easily accessible therapies.

Spinal muscular atrophy (SMA) is an inherited disorder characterized by degeneration of motor neurons and symmetrical muscle weakness and atrophy. Moyamoya syndrome (MMS) or moyamoya disease (MMD) is radiologically defined by chronic cerebrovascular occlusion with abnormal vascular network formation in the skull base. We report herein a 21-year-old female patient with limb weakness and muscular atrophy for 17 years. Electromyography revealed extensive motor neuron damage. Cranial MRA showed occlusion of bilateral anterior and middle cerebral arteries, with increased peripheral blood vessels and collateral circulation. She was diagnosed as SMA type IIIb combined with MMS following genetic testing, in which homozygous deletion of exons 7 and 8 of survival motor neuron (SMN)1 gene and 3 copies of exons 7 and 8 of SMN2 gene were detected. After treatment, the patient\'s symptoms improved. Our study found that the rare SMA and MMS co-exist. We speculated that the moyamoya phenomenon may be related to the abnormal regulation of intracranial vascular endothelial cells and smooth muscle cells in proliferation and differentiation caused by functional defects of SMN protein. The relationship between the two diseases needs to be further elucidated in future clinical work.

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Findings from mice that had their Smn gene deleted and some copies of the human SMN2 gene introduced to produce SMN protein are summarized. Symptoms due to this manipulation can be corrected only by restoring the SMN protein expression in neurones and not in muscle. The changes in muscle and neuromuscular junction (NMJ) in these mutant mice are probably due to the malfunction of the neuronal component of the NMJ i.e. the nerve terminal. The reduction of transmitter release by nerve terminals in animals with reduced SMN protein supports this notion. There is a critical period during which the presence of the SMN protein is mandatory for the survival of the motor unit and the individual. This period coincides with the most important events involved in the development of the motor unit. Results from normal genetically unaffected rats and mice show that during a critical period of development the function of the nerve terminal and the release of transmitter play a crucial role in the development of the motor neurone and muscle. The possibility that targeting the function of the nerve terminal to overcome its inability to release transmitter could benefit patients with the deletion of the SMN gene.

BACKGROUND: prenatal diagnosis in families at risk for spinal muscular atrophy (SMA) mainly of type 1 is often applied due to the high incidence, most severe and newborn outcome of the disease.
METHODS: we present our clinical experience for 36 families with history of having at least one child with homozygous deletions of the SMN1 gene between. Seventeen families requested for prenatal prediction and of these cases, 8 fetuses were diagnosed to be at risk of developing the disease and the parents decided to terminate the pregnancy. Nine fetuses were detected with no homozygous deletion of the SMN1 and reached to full term delivery. Follow-up of live born children and abortion products never led to false or negative result.
CONCLUSIONS: therefore, application of SMN1 deletion detection by simple PCR assay in families with homozygous deletion of the SMN1 gene could be suggested for prenatal prediction in such families.