All you need to know about: Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disorder characterised by the progressive loss of lower motor neurons — specialised nerve cells in the spinal cord and brainstem that control voluntary muscle movement. As these nerve cells degenerate, muscles gradually become weak and waste away (atrophy), affecting activities such as sitting, standing, walking, swallowing and, in severe cases, breathing.

SMA is estimated to affect one to two people per 1,00,000 population, with a birth incidence of one in 6,000 to one in 10,000 live births, making it one of the most common inherited neuromuscular disorders in infancy. The estimated incidence among Asian Indians is one in 9,655 live births, while the carrier frequency is one in 71 people.

Most cases are caused by changes in the SMN1 (survival motor neuron 1) gene, which produces the protein essential for motor neuron survival. Around 95% of people with the common form of SMA (5q SMA) have a homozygous deletion involving exon 7 of the SMN1 gene. The severity of the disease is influenced by the number of copies of the SMN2 gene, which produces small amounts of the same protein. Doctors classify SMA into Types 0, 1, 2, 3 and 4 based on the age at symptom onset and the highest motor milestone achieved. Type 1 is the most common form, accounting for about half of all cases.

While access to diagnosis and treatment for spinal muscular atrophy remains a challenge for many countries, including India, timely intervention can improve survival, motor function and quality of life, especially when treatment begins before symptoms appear.

What are the signs and symptoms?

The signs and symptoms vary depending on the type and severity of SMA. Infants with severe forms may have poor muscle tone, difficulty holding up the head, feeding and swallowing problems, and breathing difficulties. Children and adults with milder forms may experience delayed motor milestones, difficulty standing or walking, frequent falls, fatigue and progressive muscle weakness. Weakness usually affects muscles closest to the centre of the body before those in the hands and feet. Sensation and cognitive function are generally unaffected.

Doctors usually suspect SMA based on symptoms, developmental history and neurological examination. The diagnosis is confirmed through molecular genetic testing that identifies disease-causing changes in the SMN1 gene. Several countries have introduced newborn screening programmes because treatment is most effective before symptoms develop and before irreversible motor neuron loss occurs.

Who is most at risk?

SMA is inherited in an autosomal recessive pattern, meaning a child develops the condition only if they inherit an altered SMN1 gene from both parents. Parents who carry a single altered copy of the gene usually do not have symptoms and may be unaware they are carriers. When both parents are carriers, each pregnancy carries a 25% chance of the child having SMA, a 50% chance of the child being an unaffected carrier and a 25% chance of inheriting two unaffected copies of the gene.

While SMA can affect people of any sex or ethnic background, infants with fewer copies of the SMN2 gene are more likely to develop severe, early-onset disease, whereas those with more copies generally have milder forms with symptoms appearing later in childhood or adulthood.

What are the treatment options?

There is currently no cure for SMA. However, disease-modifying therapies introduced over the past decade have transformed treatment by either replacing the faulty SMN1 gene or increasing production of the survival motor neuron protein from the SMN2 gene. Clinical studies have shown that outcomes are best when treatment is started as early as possible, particularly before symptoms appear.

Supportive care remains an essential part of management and includes respiratory support, nutritional care, physiotherapy, occupational therapy, rehabilitation and orthopaedic care. Care is typically provided by a multidisciplinary team. Although disease-modifying therapies are available, experts continue to call for wider access to genetic testing, earlier diagnosis and comprehensive multidisciplinary care to improve outcomes for people living with SMA.