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The average prevalence at birth of proximal spinal muscular atrophy (SMA) is estimated at 1/12,000 of which approximately 1% are type 4.

Disease onset is typically in the second or third decade of life. The muscle weakness predominantly affects the legs and hip muscles and then progresses to the shoulders and arms. Waddling gait is common. Finger trembling, fasciculation and calf hypertrophy may occur. The clinical picture is similar to that seen in SMA type 3 but the motor weakness is less severe. Cognition is unaffected.

The disease is a result of degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei. Causal homozygous mutations/deletions in the SMN1 gene (5q12.2-q13.3) are responsible. SMN1 encodes the survival motor neuron protein (SMN) which is known to participate in critical pathways related to RNA processing and transport, and it is believed that motor neurons are particularly vulnerable to impairments in these processes. The disease is modified by the gene SMN2 (5q13.2), a homologous centromeric copy of SMN1 (5q13.1), the copy number of which is inversely correlated to disease severity.

The diagnosis is based on clinical history and examination. In patients with SMN1 anomalies, the diagnosis may be confirmed by genetic testing. Electromyography and muscle biopsy may be necessary.

Differential diagnoses include the amyotrophic lateral sclerosis, primary lateral sclerosis, Kennedy disease, myasthenia gravis, and carbohydrate metabolism disorders.

Prenatal diagnosis is possible for families in which the mutations in the SMN1 gene have been identified.

The SMN1 gene deletions are transmitted in an autosomal recessive manner. Genetic counseling should be provided.

Management is symptomatic, involves a multidisciplinary approach, and aims to improve quality of life. Physiotherapy and occupational therapies are recommended. Walking aids may be required as the disease progresses. Documenting functional status in SMA is important, since all patients show limitations in daily functioning. Nusinersen, an antisense oligonucleotide, is now approved for treatment of SMA in Europe and the USA. There is no data currently available concerning treatment in SMA type 4; however, it is believed that nusinersen may be most effective when started as soon as possible after diagnosis. Other clinical trials are ongoing to identify other potential treatments.

Affected individuals have a normal life expectancy. The greatest morbidity is on quality of life, with impairment of daily activities. Some patients may lose the ability to walk.