SMA is a genetic neuromuscular disorder characterised by progressive muscle weakness and wasting, due to the degeneration of motor neurons.^1,4 Untreated, it is the most common genetic cause of infant mortality and an important cause of motor delay or regression in children that should not be missed.¹

SMA is an autosomal recessive condition caused by a deficiency in SMN protein due to a mutated or deleted SMN1 gene.² This protein is required for the survival of motor neurons. Without the SMN protein, motor neuron loss in the brainstem and spinal cord occurs, leading to subsequent denervation and atrophy of muscles.^1,3

SMA affects one in 10,000 live births and the carrier frequency for SMN1 mutations is estimated to be between one in 38 and one in 70.^1,4 Unlike other genetic conditions, SMA affects individuals of all ethnic groups.⁸

While there is no cure for SMA, treatments are now available on the Pharmaceutical Benefits Scheme (PBS). Nusinersin and risdiplam increase production of functional SMN protein (ongoing treatment is required), while single-dose gene therapy with onasemnogene abeparvovec delivers a functional copy of the SMN1 gene to motor neurons. These treatments are most effective when administered early, preferably presymptomatically.^9–11

Beyond the prompt initiation of drug treatment, timely diagnosis also aids early intervention and support measures, including the set-up of a multidisciplinary care team for the child and family. This ensures adequate support structures are in place prior to disease progression or the onset of complications, which can help to ease the family’s burden.¹²

An infant presenting with motor weakness and delay in the setting of normal cognition should raise a high index of suspicion for SMA. This suspicion should be maintained regardless of whether the infant appears superficially normal, as infants with SMA often look bright and alert with normal facial expression.^5,6

Parents may additionally report that their child seems floppy like a rag doll, struggles to lift their head up or do ‘tummy time’, isn’t on par with other kids of the same age, or simply that something is not quite right – all of which should augment suspicion.^7,13,14 It is important to take the report of parents seriously, as studies indicate that parental concern is a fairly accurate predictor of developmental problems.^15,16

Other characteristic red flags to be aware of include:^5,6

• muscle weakness (with or without atrophy)
• hypotonia (relaxed tone, ‘floppy’)
• poor head control (eg head lag when pulled to sit, if age >5 months)
• tongue fasciculations
• ‘frog leg’ posture when lying
• reduced or absent tendon reflexes.

Given the importance of early diagnosis, children suspected of having SMA or other neuromuscular disease should be urgently referred for specialist assessment – hypotonia and motor weakness in a child aged <2 years always requires urgent investigation, especially if accompanied by delay.

Ideally, you should refer the patient to a paediatric neurologist or tertiary paediatric neuromuscular clinic, indicating the urgency of your referral. If access to subspecialty care is limited, refer urgently to a general paediatrician for further assessment, stating that you are concerned about a possible SMA diagnosis.

Carrier screening (ie genetic testing) can identify individuals and couples at increased risk of having a child with SMA.⁸ Currently, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommends that information about carrier screening – including the three-panel screen for SMA, fragile X syndrome and cystic fibrosis – be provided to all women and couples planning a pregnancy or in their first trimester.

Learn more about carrier screening for rare hereditary diseases.