SMA | RACGP – Beware the Rare

Untreated, SMA is the most common genetic cause of infant mortality, affecting one in 10,000 live births.¹

What causes SMA?

SMA is an autosomal recessive condition caused by a deficiency in SMN protein due to a mutated or deleted SMN1 gene.² A lack of SMN protein leads to motor neuron loss in the brainstem and spinal cord (‘infant motor neuron disease’).^1,3
SMA autosomal recessive inheritance pattern²

Carrier frequency for SMN1 mutations is estimated to be between one in 38 and one in 70.^1,4
What’s the clinical imperative?

While there is no cure for SMA, treatments are now available.

Delays in referral may delay drug treatment, leading to further loss of motor neurons and, in turn, motor function.
Red flags in a floppy, weak child^1,5,6
- Progressive proximal muscle weakness and atrophy
- Hypotonia (eg ‘frog leg’ posture when lying)
- Poor head control (eg head lag when pulled to sit, if age >5 months)
- Reduced or absent tendon reflexes
- Bright and alert (unaffected cognition).
Infants with SMA are not dysmorphic. This may lead clinicians to dismiss the significance of other signs such as relaxed tone and delayed motor milestones.
An infant or child presenting with motor weakness and delay in the setting of normal cognition should be referred urgently for specialist input, regardless of whether they appear superficially normal.

A common cause of diagnostic delay is initial referral to a paediatric allied health service, physiotherapist or general paediatrician rather than to a paediatric neurologist.⁷
In most cases, patients experience superior outcomes with timely diagnosis and early intervention.

Do not take a ‘wait and see’ approach with a concerning clinical impression. Do take a ‘let’s play it safe and refer early’ approach.

Accredited education and learning

Click the link to complete an online education module on what healthcare professionals need to know about recognising the red flags for spinal muscular atrophy and when to refer to a specialist. This learning module is an RACGP-approved CPD activity under the RACGP CPD Program and is suitable for general practitioners, practice nurses, obstetricians, fertility specialists, general paediatricians and maternal child health nurses.

Know the signs

Clinical resources

Click to view or download any of these resources.

Patient resources

The following resource was developed for patients by SMA Australia.

SMA patient handout

Download PDF

Click through to the above websites for further information and support for families and carers

Frequently asked questions

What is SMA?

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

What causes SMA?

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

How common is SMA?

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

Why is early referral and diagnosis important?

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

How does SMA present?

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.

When should you refer?

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.

Who should you refer the child to?

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.

Can SMA be prevented?

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.

References

Darras B. Spinal muscular atrophies. Pediatr Clin N Am 2015;62(3):743–66.
Kolb S, Kissel J. Spinal muscular atrophy. Arch Neurol 2011;68(8):979–84.
FriesenW, Massenet S, Paushkin S, Wyce A, Dreyfuss G. SMN, the product of the spinal muscular atrophy gene, binds preferentially to dimethylarginine-containing protein targets. Mol Cell 2001;7(5):1111–17.
Farrar M, Park SB, Vucic S, et al. Emerging therapies and challenges in spinal muscular atrophy. Ann Neurol 2017;81(3):355–68.
Kolb S, Kissel J. Spinal muscular atrophy. Neurol Clin 2015;33(4):831–46.
D’Amico A, Mercuri E, Tiziano F, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis 2011;6:71.
Lawton S, Hickerton C, Archibald A, McClaren B, Metcalfe S. A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy. Eur J Hum Genet 2015;23(5):575–80.
Sugarman E, Nagan N, Zhu H, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of >72400 specimens. Eur J Hum Genet 2012;20(1):27–32.
Australian Government Services Australia. Spinal Muscular Atrophy. Canberra; Services Australia, 2022. Available at www.servicesaustralia.gov.au/spinal-muscular-atrophy?context=23021 [Accessed 24 January 2023].
Butterfield RJ. Spinal Muscular Atrophy Treatments, Newborn Screening, and the Creation of a Neurogenetics Urgency. Semin Pediatr Neurol 2021;38:100899.
Newson AJ, Dive L, Cini J, et al. Ethical aspects of the changing landscape for spinal muscular atrophy management in Australia. Aust J Gen Pract 2022 Mar;51(3):131–35.
Lin C, Kalb S, Yeh W. Delay in diagnosis of spinal muscular atrophy: A systematic literature review. Pediatr Neurol 2015;53:293–300.
Lurio J, Peay H, Mathews K. Recognition and management of motor delay and muscle weakness in children. Am Fam Physician 2015;91(1):38–45.
National Task Force for Early Identification of Childhood Neuromuscular Disorders. Signs of weakness by parent report. US: National Task Force for Early Identification of Childhood Neuromuscular Disorders, 2020. Available at www.childmuscleweakness.org/know-the-signs/signs-of-weakness-by-parent-report [Accessed 24 January 2023].
Oberklaid F, Drever K. Is my child normal? Milestones and red flags for referral. Aust Fam Physician 2011;40(9):666–70.
Glascoe F. Evidence-based approach to developmental and behavioural surveillance using parents’ concerns. Child Care Health Dev 2000;26(2):137–49.

Acknowledgements

The RACGP gratefully acknowledges the contributions from the SMA and carrier screening expert advisory group in developing this education material:

Professor Jon Emery, GP, Herman Professor of Primary Care Cancer Research, University of Melbourne
Professor Martin Delatycki, Clinical Director, Victorian Clinical Genetics Services
Dr James Best, GP, Chair, Child and Young Person’s Health Network, RACGP
Associate Professor Michelle Farrar, paediatric neurologist, UNSW Sydney
Ms Julie Cini, CEO, SMA Australia
Professor Steve Robson, past president, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists