Signs and Symptoms

Signs and Symptoms

One of the pathological hallmarks of spinal muscular atrophy (SMA) is the degeneration of anterior horn cells in the spinal cord and motor nuclei in the lower brainstem.1 Alpha motor neurons are preferentially affected, so the disease is limited to the motor system rather than the sensory system.2 With this progressive loss of motor neuron function, affected individuals exhibit proximal voluntary muscle weakness of the legs, arms, and trunk.3 Despite being a motor neuron disease, some of the clinical features of SMA appear to be more consistent with myopathy.2,4 The distribution of muscle atrophy/weakness follows a pattern, but it is unevenly distributed throughout the body. Specifically, proximal muscles tend to be more significantly involved than distal muscles.4 Likewise, there is generally greater weakness in the legs than the arms, and greater weakness in the arms than the face and the pulmonary diaphragm.4 

Despite the fact that SMA is caused by a progressive motor neuron loss, the severity of muscle weakness correlates with the age at which symptoms first present—muscle strength can remain stable for months or years after diagnosis.2,4 Stated another way, for all types other than SMA type 0, there is a pre-symptomatic stage followed by a period of rapid deterioration in muscle function followed in turn by static stability of symptoms.5

Neonates with SMA type 0 are typically born with hypotonia and exhibit severe muscular weakness.6,7 One usually cannot elicit spinal reflexes, and the facial muscles may be paralyzed bilaterally (i.e. facial diplegia). Clinicians caring for an infant with SMA type 0 may notice multiple joint contractures, a condition called arthrogryposis. Indeed, joint contractures may be evident on prenatal ultrasound.8 Affected children generally require almost immediate external ventilation after parturition.

Individuals with SMA type 1 will exhibit signs and symptoms of the disease between zero and six months of age. Children never acquire the ability to sit upright without assistance and are sometimes referred to as “non-sitters.” Children with SMA type 1 will exhibit severe muscle weakness bilaterally and hypotonia. Over time progressive muscle weakness will affect bulbar musculature and intercostal muscles, interfering with the ability to chew/swallow and breathe. Poor head control is a rather common sign of SMA type 1.5 Clinicians may note in “frog leg” posture as children lie flat on their backs, which indicates lower extremity weakness.6

Individuals with SMA type 2 generally exhibit signs and symptoms of the disease between six and 18 months of age. A portion of children with SMA type 2 are able to sit up without assistance, while others are able to sit unattended after being placed in a sitting position.2,9 Importantly, children with this type of SMA will not stand or ambulate without assistance. This group is sometimes referred to as “sitters” but this is not always accurate—some children will be able to sit up, others will not, and many will eventually lose this ability late in the disease. Thus, the sitters nomenclature, which is important for directing treatment, is based on the child’s current level of function rather than strict SMA type.

Muscle weakness is a prominent feature in children with SMA type 2, primarily affecting the legs. Chewing and swallowing difficulties may lead to slowed weight gain. Weakness in respiratory muscles may result in a weakened cough and breathing trouble, which places these patients at greater risk for respiratory problems caused by aspiration and the inability to clear secretions. Virtually all patients in this group will develop some form of progressive scoliosis. Respiratory muscle weakness and scoliosis may combine to result in restrictive lung disease pattern.10

Patients with SMA type 3 exhibit similar symptoms as those with type 2 disease, though generally to a lesser degree. Proximal muscle weakness predominantly affects the legs. While there may be difficulty swallowing and scoliosis, it is less common and less severe than in children with lower numbered types of SMA. Unlike SMA type 2, children with SMA type 3 eventually gain the ability to walk independently (and are sometimes called “walkers”), yet may lose this ability at later stages in the disease progression. “Walkers” may develop a foot eversion abnormality.11 This sign and a coarse tremor may be clues to the diagnosis.11

The signs and symptoms of SMA type 4 are relatively mild. Patients can walk, swallow, and breath normally.2,4


1. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and Management of Spinal Muscular Atrophy: Part 1: Recommendations for Diagnosis, Rehabilitation, Orthopedic and Nutritional Care. Neuromuscul Disord. 2018;28(2):103-115. doi:10.1016/j.nmd.2017.11.005 

2. Baioni MT, Ambiel CR. Spinal Muscular Atrophy: Diagnosis, Treatment and Future Prospects. J Pediatr (Rio J). 2010;86(4):261-270. doi:doi:10.2223/JPED.1988 

3. Wang CH, Finkel RS, Bertini ES, et al. Consensus Statement for Standard of Care in Spinal Muscular Atrophy. Journal of Child Neurology. 2007;22(8):1027-1049. doi:10.1177/0883073807305788 

4. Sumner CJ. Molecular Mechanisms of Spinal Muscular Atrophy. J Child Neurol. 2007;22(8):979-989. doi:10.1177/0883073807305787 

5. Arnold WD, Kassar D, Kissel JT. Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era. Muscle Nerve. 2015;51(2):157-167. doi:10.1002/mus.24497 

6. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurol Clin. 2015;33(4):831-846. doi:10.1016/j.ncl.2015.07.004 

7. MacLeod MJ, Taylor JE, Lunt PW, Mathew CG, Robb SA. Prenatal Onset Spinal Muscular Atrophy. Eur J Paediatr Neurol. 1999;3(2):65-72. doi:10.1053/ejpn.1999.0184 

8. Grotto S, Cuisset JM, Marret S, et al. Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients. J Neuromuscul Dis. 2016;3(4):487-495. doi:10.3233/JND-160177 

9. Russman BS. Spinal Muscular Atrophy: Clinical Classification and Disease Heterogeneity. J Child Neurol. 2007;22(8):946-951. doi:10.1177/0883073807305673 

10. Iannaccone ST. Modern Management of Spinal Muscular Atrophy. J Child Neurol. 2007;22(8):974-978. doi:10.1177/0883073807305670 

11. Moosa A, Dubowitz V. Spinal Muscular Atrophy in Childhood. Two Clues to Clinical Diagnosis. Arch Dis Child. 1973;48(5):386-388.