Spinal Muscular Atrophy (SMA)

What causes SMA

Most SMA (5q SMA) is caused by a deletion or mutation of both copies of the SMN1 gene, which makes survival motor neuron (SMN) protein. Motor neurons need this protein to survive.

A nearby backup gene, SMN2, makes a small amount of working SMN protein. The number of SMN2 copies varies between people: more copies generally mean milder disease. This is why SMA severity varies so much.

SMA is autosomal recessive. When both parents are carriers, each child has a 25 percent chance of SMA.

Types of SMA

With early treatment, many children now achieve milestones beyond their predicted type.

Symptoms

• muscle weakness affecting the legs more than the arms, and muscles closest to the trunk most
• floppiness (hypotonia) in infants, "frog-leg" posture
• weak cry and cough, difficulty feeding and swallowing
• bell-shaped chest and belly breathing from weak chest muscles
• tongue twitching (fasciculations)
• delayed or lost motor milestones
• tremor of the hands
• scoliosis and joint contractures
• normal intelligence and sensation

Diagnosis

• newborn screening: SMA is on the US Recommended Uniform Screening Panel, and nearly all states screen at birth using a blood spot
• genetic testing: confirms absence of SMN1 and counts SMN2 copies
• carrier testing for parents and relatives
• EMG and muscle biopsy are rarely needed now

Treatment

Disease-modifying therapies

All three increase SMN protein and work best when started early, ideally before symptoms:

• nusinersen (Spinraza): an antisense drug injected into the spinal fluid every 4 months after initial loading doses; for all ages
• risdiplam (Evrysdi): a daily oral liquid or tablet that boosts SMN2 production; for all ages
• onasemnogene abeparvovec (Zolgensma): a one-time IV gene therapy delivering a working SMN1 gene, for children under 2 in the US

Supportive and multidisciplinary care

• breathing: cough assist devices, airway clearance, noninvasive ventilation (BiPAP), vaccinations
• nutrition: swallowing assessment, feeding tubes when needed
• orthopedics: physical therapy, braces, wheelchairs, scoliosis surgery
• therapies: occupational and speech therapy
• care coordination at a neuromuscular center

Outlook

Before treatments, most children with type 1 did not survive beyond age 2. Now, children treated before symptoms often sit, stand and walk, and many treated after symptom onset gain milestones and live longer. Long-term outcomes are still being studied. Types 3 and 4 have normal or near-normal life expectancy.

SMA differs from muscular dystrophy, which damages the muscles themselves, and from ALS, which affects both upper and lower motor neurons in adults.

Frequently asked questions

What is spinal muscular atrophy?

SMA is a genetic disease in which nerve cells in the spinal cord that control muscles die, causing progressive muscle weakness and wasting. It affects movement, breathing and swallowing. Severity ranges from life-threatening in infancy to mild in adulthood.

What are the first signs of SMA in babies?

Early signs include floppiness, weak arm and leg movements, poor head control, a weak cry and cough, feeding difficulty and belly breathing. Many babies are now identified by newborn screening before signs appear.

Is there a cure for SMA?

There is no complete cure, but three treatments (nusinersen, risdiplam and onasemnogene gene therapy) can halt or slow the disease and improve motor function, especially when started early. Gene therapy is a one-time treatment.

How is SMA inherited?

SMA is usually autosomal recessive. Both parents are typically healthy carriers, and each child has a 25 percent chance of having SMA. About 1 in 50 people is a carrier, and carrier testing is available.

What is the life expectancy with SMA?

It depends on the type and treatment. Untreated type 1 is often fatal by age 2, but treated children are living much longer with better function. People with types 3 and 4 usually have a normal life expectancy.