Spinal Muscular Atrophy (SMA)

Diagnosis

The first steps in diagnosis of a neuromuscular disease are usually an in-office physical examination and family history, with some simple tests to distinguish spinal muscular atrophy (SMA) from similar conditions (such as muscular dystrophy). Muscle weakness and hypotonia should be the first signs that raise suspicion for SMA in babies. Other signs can help to confirm the diagnosis, such as a history of motor difficulties, loss of motor skills, proximal muscle weakness, hyporeflexia (absence of reflexes), tongue fasciculations (involuntary twitches), and signs for low motor neuron disease.

A doctor may order a blood test for an enzyme called creatine kinase (CK), which leaks out of muscles that are deteriorating. This is a nonspecific test because CK levels are elevated in many neuromuscular diseases, but it’s often a useful test. High blood CK levels aren’t harmful in and of themselves, but they do indicate that muscle damage has occurred. Usually, CK levels are normal in patients diagnosed with SMA type 1 but can be a slightly elevated in patients diagnosed with other types of SMA, such as types 2 and 3. As a result, SMA types 2 and 3 might be confused with other neuromuscular disease, such as Duchenne muscular dystrophy (DMD).

A doctor probably will recommend genetic testing if SMA is suspected because this is the least invasive and most accurate way to diagnose chromosome 5-related SMA (types 1-4). Genetic testing requires only a blood sample. The primary genetic test for SMA detects the deletion of exon 7 in both copies of the SMN1 gene, the most common cause of the disease. If this test is negative or inconclusive, follow-up DNA sequencing may be performed to identify point mutations that could also lead to SMA. Given the hereditary nature of SMA, genetic testing has broader implications for family members, which should be carefully considered (see Causes/Inheritance).

As of February 2024, all 50 US states and Washington, D.C. have included SMA in their newborn genetic screening programs. However, newborn screening may miss ~2-5% of cases, and older children with SMA who were not screened at birth may remain undiagnosed. Therefore, clinical awareness of diagnostic criteria remains crucial for identifying symptomatic cases.

In rare cases, doctors may order a muscle biopsy, which involves taking a small sample of muscle tissue, usually from the thigh, and looking at it under a microscope.

Other tests sometimes used to diagnose SMA include one that measures nerve conduction velocity — the speed with which signals travel along nerves — and one that measures the electrical activity in muscle, called an electromyogram, or EMG. Nerve conduction velocity tests involve sensations that feel like mild electric shocks, and EMGs require that short needles be inserted in the muscles.

Additional reading

• Schroth M, Deans J, Arya K, Castro D, De Vivo DC, Gibbons MA, Ionita C, Kuntz NL, Lakhotia A, Neil Knierbein E, Scoto M, Sejersen T, Servais L, Tian C, Waldrop MA, Vázquez-Costa JF. Spinal Muscular Atrophy Update in Best Practices: Recommendations for Diagnosis Considerations. Neurol Clin Pract. 2024 Aug;14(4):e200310. doi: 10.1212/CPJ.0000000000200310. Epub 2024 May 24. Erratum in: Neurol Clin Pract. 2025 Feb;15(1):e200386. doi: 10.1212/CPJ.0000000000200386. PMID: 38915908; PMCID: PMC11195435.
• Prior TW, Leach ME, Finanger EL. Spinal Muscular Atrophy. 2000 Feb 24 [Updated 2024 Sep 19]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1352/

Last reviewed by July 2025 by Aravindhan Veerapandiyan, MD