How Does Spinal Muscle Atrophy Present?

Patient Presentation
A 4-month-old male came to clinic for his well child examination. His mother’s only concern was when he should be taking solid food. He was smiling, cooing and could roll from front to back when laid prone. The past medical history showed a former 36 week premature infant because of maternal chrorioamnionitis. Initially he had temperature instability for several hours and mild hypotonia. His initial screening and repeated laboratory testing were negative, but he received presumptive antibiotics for 5 days because of the temperature instability and hypotonia.

The pertinent physical exam revealed a smiling infant with growth parameters in the 25-50% with normal vital signs. His examination was normal with normal tone and strength. He still had a small head lag when pulled to sitting from a recumbent position. The diagnosis of a healthy male was made. The pediatrician discussed not to start solid foods currently as the child still had a head lag but explained that this was normal even for a child who was not born prematurely. After the visit the medical student who was following the pediatrician asked several questions about the differential diagnosis of hypotonia. The pediatrician explained that the most common cause at birth was something that could usually be fixed fairly quickly such as an electrolyte problem or presumed sepsis, but that other causes were possible. She asked about some genetic causes and wanted to know when spinal muscle atrophy presented. The pediatrician discussed that it could start quite early and could be very aggressive in its increasing weakness or that it could be much milder. “I’ve only taken care of a few patients and they were infants when they were diagnosed. They had had severe disease and many problems” he explained.

Discussion
Muscle tone is the slight tension that is felt in a muscle when it is voluntarily relaxed. It can be assessed by asking the patient to relax and then taking the muscles through a range of motion such as moving the wrists, forearm and upper arm. Muscle strength is the muscle’s force against active resistance. Impaired strength is called weakness or paresis. There are 5 levels of muscle strength. Hypotonia can occur with or without weakness. Decreased fetal movements in utero, persistent hypotonia and difficulty feeding are more consistent with congenital rather than an acquired hypotonia. Common treatable conditions such as hypothyroidism, electrolyte abnormalities and metabolic problems can often be ruled in or out relatively quickly. A differential diagnosis of hypotonia with and without muscle weakness can be found here. A differential diagnosis of hypotonia in infants can be found here.

Learning Point
Spinal muscle atrophy (SMA) was first described in the 19th century and is an autosomal dominant neuromuscular disease caused by a deletion or mutation in the motor neuron 1 gene on chromosome 5q13. It causes anterior horn cell loss in the spinal column and brain stem with progressive symmetric proximal muscle weakness. Patients also present with respiratory and orthopaedic problems. Hypotonia, decreased or absent deep tendon reflexes, muscle fasciculations and muscle contractions can also occur.

The gene frequency is 1 in 40-70 in the general population but the disease is less common than expected (varies 1:6000 to 1:25,000 births) most likely due to fetal loss or very mild forms that are undiagnosed. SMA1 gene is deleted in 95% of patients so a functional protein is not made. SMA2 is a modifier gene that has protective effects on the protein but is variable in its actions. SMA is detected by genetic testing. DNA assays of dried blood spots are possible making SMA a candidate for newborn screening.

There is no definite cure or specific treatment. Some treatments attempt to upregulate the SMA2 gene or to produce more protein such as valproic acid or hydroxyurea. Neuroprotective medications, such as gabapentin, are being evaluated Gene and cell therapy are also being studied.

Update in September 2021: Currently there are 3 Federal Drug Administration drugs approved to treat SMA. These alter the disease course and life expectancy. Outcomes are better with earlier treatment so early diagnosis is important.