Spinal muscular atrophy

Spinal muscular atrophy
Other names	Autosomal recessive proximal spinal muscular atrophy, 5q spinal muscular atrophy
Location of neurons affected by spinal muscular atrophy in the spinal cord
Specialty	Neurology
Symptoms	Progressive muscle weakness[1]
Complications	Scoliosis, joint contractures, pneumonia[2]
Usual onset	Mutation is congenital, symptoms start varies by type
Duration	Lifelong
Types	Type 0 to type 4[2]
Causes	Mutation in SMN1[2]
Diagnostic method	Genetic testing[1]
Differential diagnosis	Congenital muscular dystrophy, Duchenne muscular dystrophy, Prader-Willi syndrome[2]
Treatment	Supportive care, medications[1]
Medication	Nusinersen, onasemnogene abeparvovec, Risdiplam
Prognosis	Varies by type[2]
Frequency	1 in 10,000 people[2]

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting.^[3][4][5] It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death.^[6] It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first.^[7][8] Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures.^[2][8]

The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types.^[4]

Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene^[1][2] which encodes SMN, a protein necessary for survival of motor neurons.^[8] Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles.^[8] Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing.^[9][1]

Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo).^[1][10] The incidence of spinal muscular atrophy worldwide varies from about 1 in 4,000 births to around 1 in 16,000 births,^[11] with 1 in 7,000 and 1 in 10,000 commonly quoted for Europe and the US respectively.^[2]

Outcomes in the natural course of the disease vary from death within a few weeks after birth in the most acute cases to normal life expectancy in the protracted SMA forms.^[8] The introduction of causative treatments in 2016 has significantly improved the outcomes. Medications that target the genetic cause of the disease include nusinersen, risdiplam,^[12] and the gene therapy medication onasemnogene abeparvovec. Supportive care includes physical therapy, occupational therapy, respiratory support, nutritional support, orthopaedic interventions, and mobility support.^[1]