Proximal Spinal Muscular Atrophy (SMA)

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ICD10 via Orphanet 33 G12.0 G12.1 Orphanet 58 ORPHA70

SNOMED-CT via HPO 68 134291007 199612005 22033007 234097001 274523007 30213001 398151007 398152000 5468008 84445001 86203003 more UMLS 71 C4024957

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 70 Definition Proximal spinal muscular atrophies are a group of neuromuscular disorders characterized by progressive muscle weakness resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei. Epidemiology Prevalence is estimated at around 1/30,000. Clinical description Four subtypes have been defined according to the age of onset and severity of the disease: type 1 (SMA1), the most severe form, with onset before six months of age; type 2 (SMA2), with onset between 6 and 18 months of age, type 3 (SMA3), with onset between childhood and adolescence, and type 4 (SMA4), the least severe form, with adult onset (see these terms). All types are characterized by muscle weakness and atrophy of varying severity, particularly affecting the lower limbs and respiratory muscles. The weakness is almost always symmetric and progressive. Scoliosis , muscle retractions, and joint contractures may occur. Constipation and gastroesophageal reflux are frequent. Etiology Around 95% of cases of SMA are caused by homozygous deletions (either of exon 7, or of exons 7 and 8) in the SMN1 gene (5q12.2-q13.3) encoding the SMN (survival motor neuron) protein . A second SMN gene (SMN2 ; 5q13.2) has also been identified and contributes to the production of only 10% of the full-length SMN protein. However, although there is some variation, disease severity in SMA is inversely correlated with the number of copies of the SMN2 gene, with patients with three or four copies more frequently manifesting SMA3/4, rather than SMA1. Deletions of the NAIP (5q13.1) gene have also been identified and may play a role in modifying disease severity. Diagnostic methods Diagnosis is based on clinical history and examination and can be confirmed by genetic testing . Electromyography and muscle biopsy may also be performed. Differential diagnosis Differential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms). Antenatal diagnosis Antenatal diagnosis is feasible through molecular analysis of amniocytes or chorionic villus samples. Genetic counseling Transmission of SMN1 and NAIP deletions is autosomal recessive . Around 2% of cases are caused by de novo mutations . Genetic counseling should be offered to patients and their families. Management and treatment Clinical trials are ongoing to identify potential drug treatments for SMA, mainly targeted towards increasing the levels of the full length SMN protein. However, at present, management remains symptomatic, involving a multidisciplinary approach that aims to improve quality of life. Physiotherapy and occupational and respiratory therapies are necessary. Noninvasive ventilation and gastrostomy may be required. Antibiotic therapy is used in case of pulmonary infection. The scoliosis and joint manifestations may require surgical correction. Patients may require a wheelchair, or use a corset/back brace for support. Prognosis The prognosis depends on the severity of the disease, which generally correlates with the age of onset: earlier-onset forms are generally associated with a poor prognosis, whereas life expectancy may be close to normal in later-onset forms. Death may occur due to respiratory insufficiency and infections. Visit the Orphanet disease page for more resources.

MalaCards based summary : Proximal Spinal Muscular Atrophy, also known as sma, is related to autosomal dominant proximal spinal muscular atrophy and spinal muscular atrophy with progressive myoclonic epilepsy. An important gene associated with Proximal Spinal Muscular Atrophy is SPG7 (SPG7 Matrix AAA Peptidase Subunit, Paraplegin), and among its related pathways/superpathways are Golgi-to-ER retrograde transport and Cytoskeletal Signaling. The drugs Cholinergic Agents and Pyridostigmine Bromide have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and spinal cord, and related phenotypes are muscular hypotonia and emg abnormality

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