Proximal Spinal Muscular Atrophy

External Ids:

Orphanet 59 ORPHA70 ICD10 via Orphanet 34 G12.0 G12.1

SNOMED-CT via HPO 69 234097001 30213001 398151007 398152000 84445001 199612005 22033007 86203003 134291007 5468008 274523007 more UMLS 73 C4024957

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 70Disease definitionProximal 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.EpidemiologyPrevalence is estimated at around 1/30,000.Clinical descriptionFour 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.EtiologyAround 95% of cases of SMA are caused by homozygousdeletions (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 methodsDiagnosis is based on clinical history and examination and can be confirmed by genetic testing. Electromyography and muscle biopsy may also be performed.Differential diagnosisDifferential diagnoses include amyotrophic lateral sclerosis, congenital muscular dystrophies, congenital myopathies, primary lateral sclerosis, myasthenia gravis, and carbohydrate metabolism disorders (see these terms).Antenatal diagnosisAntenatal diagnosis is feasible through molecular analysis of amniocytes or chorionic villus samples.Genetic counselingTransmission 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 treatmentClinical 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.PrognosisThe 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 spinal muscular atrophy, type i and spinal muscular atrophy, type iv. An important gene associated with Proximal Spinal Muscular Atrophy is SMN1 (Survival Of Motor Neuron 1, Telomeric), and among its related pathways/superpathways are Cytoskeletal Signaling and COPI-independent Golgi-to-ER retrograde traffic. The drugs Pyridostigmine Bromide and Cholinergic Agents have been mentioned in the context of this disorder. Affiliated tissues include testes, spinal cord and brain, and related phenotypes are preauricular skin tag and lymphedema

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Negative genetic interaction between BLM-/- and BLM+/+	GR00255-A-1	8.92	APOE BICD2 LMNA SMNDC1

Search NIH Clinical Center for Proximal Spinal Muscular Atrophy

Search GEO for disease gene expression data for Proximal Spinal Muscular Atrophy.