China
Africa
Explore chapters and articles related to this topic
Diaphragm Ultrasound in Patients with Neuromuscular Disorders
Published in Massimo Zambon, Ultrasound of the Diaphragm and the Respiratory Muscles, 2022
Spinal muscular atrophies (SMA) are neuromuscular disorders in relation to defect in the survival motor neuron (SMN1) gene. The disease is characterized by a progressive degeneration of spinal cord motor neurons and patients disclose weakness and atrophy of skeletal muscles (23). The most severe form is the type 1 SMA that is characterized by weakness, severe hypotonia, swallowing disorders and respiratory failure over the first year of life (24). Ultrasound can be used to assess patients in this disease particularly, SMA patients with acute respiratory distress (25).
Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
SMA is an autosomal recessive condition caused by a deletion of a segment of DNA in exon 7 and exon 8 in the SMN1 (survival motor neuron) gene located on chromosome 5. Rarely, SMA is caused by a point mutation in the SMN1 gene. There does not appear to be a correlation between the type of SMN1 pathogenic variant and disease severity. SMN2 generates small amounts of SMN protein. The number of copies of SMN2 does correlate with SMA phenotype. Individuals with fewer copies of SMN2 typically have more severe forms of SMA (type I or II). See Table 6.10.
Chronic Denervation Myopathy
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
Spinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular disease characterized by degeneration of spinal cord motor neurons. It is caused by homozygous mutations of survival motor neuron 1 (SMN1) gene on both copies of chromosome 5q. The presence of a human unique SMN2 as a backup gene provides partially functional SMN protein and affects the severity of the phenotype. SMA was originally described in two infant brothers by Guido Werdnig in 1891 and in seven additional cases by Johan Hoffmann from 1893 to 1900. The International Consortium on SPA sponsored by the Muscular Dystrophy Association in 1991 suggested phenotype classification of SMA based on the highest level of motor function and age of onset (Table 21.2). Subsequent modifications added a type I for adult-onset cases and included a type 0 for patients with prenatal onset and death within weeks.
Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective
Published in Expert Review of Neurotherapeutics, 2023
Lakshmi Balaji, Michelle A Farrar, Arlene M D’Silva, Didu S Kariyawasam
Spinal muscular atrophy (SMA) is a genetic neuromuscular disease, associated with a high morbidity and mortality related to muscle weakness. Historically, the classification of SMA has been described by age of onset of muscle weakness and maximal motor milestone attained. Symptom onset ranges from fetal (Type 0), to before 7 months (Type 1, non-sitter), between 7 and 18 months (Type 2, sitter), after 18 months (Type 3, walker) and during adulthood (Type 4). Biallelic pathogenic variants in the survival motor neuron 1 (SMN1) gene cause loss of functional SMN protein [1], the latter appearing critical for spinal motor neuron development, function, and maintenance [2]. The paralogous SMN2 gene produces low but insufficient levels of the functional SMN protein [3]. The number of SMN2 genes varies between individuals and correlates inversely with disease severity. Whilst not absolute, SMN2 is considered an important modifier of SMA phenotype [4].
Risdiplam: an investigational survival motor neuron 2 (SMN2) splicing modifier for spinal muscular atrophy (SMA)
Published in Expert Opinion on Investigational Drugs, 2022
Theodora Markati, Gemma Fisher, Sithara Ramdas, Laurent Servais
Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that is characterised by progressive loss of motor neurons leading to progressive muscle weakness, atrophy, and motor and respiratory impairment. The most common form, called 5q-SMA, is caused by a homozygous deletion or loss-of-function mutations in the survival of motor neuron 1 (SMN1) gene on locus 5q13 of chromosome 5, which codes for the homonymous survival motor neuron (SMN) protein [1,2]. 5q-SMA, henceforth called SMA, occurs in 1 in 10,000 live births and it is one of the leading genetic causes of childhood mortality. SMA is characterised by progressive initially proximal and axial muscle weakness, decreased or absent deep tendon reflexes, muscle atrophy, and – in the most severe forms without intervention – bulbar dysfunction and progressive respiratory failure as the cause of early death [3].
An evaluation of onasemnogene abeparvovec for spinal muscular atrophy (SMN1)
Published in Expert Opinion on Orphan Drugs, 2021
Megan A. Waldrop, Anne M. Connolly, Jerry R. Mendell
SMA is a progressive neurodegenerative disease affecting the motor neurons in the brain stem and spinal cord with an incidence of approximately 1 in 10,000 [2]. SMA is caused by homozygous loss-of-function mutations in the SMN1 gene located on chromosome 5q13. SMN1 produces the survival motor neuron (SMN) protein, which is essential for health and function of motor neurons. The absence of SMN is not compatible with life. Individuals with SMA have varying copies of a back-up gene, SMN2, which has a single-nucleotide change in exon 7 resulting in altered splicing and production of a nonfunctional SMN protein (Figure 1). However, a small amount of nonspliced transcript (~10%), and thus a fully functional SMN protein, is made from each SMN2 copy [3]. SMA is categorized into five types based on disease severity, with Type 0 being the most severe and Type 4 the least severe. As expected, more copies of SMN2 leads to more functional SMN protein and a milder phenotype [Table 1[4,5]]. When untreated, most children with type 1 SMA (the most common form; typically, with two copies of SMN2) die by age 2 [6,7].