Spinal muscular atrophy (SMA) is a disorder of the neuromuscular system that manifests as weakness and hypotonia.1 There are some identifiable factors that influence the severity of weakness or hypotonia in SMA patients. Homozygous deletion of the gene SMN1 with a concurrent deletion of NAIP, for instance, is associated with severe hypotonia, as well as earlier onset and worse outcomes in SMA patients.3
The severity of weakness and hypotonia seen in SMA also varies according to the type of SMA a patient has. SMA type 0 patients have profound hypotonia that includes fewer fetal movements in utero.4 Similarly, X-linked infantile SMA (XL-SMA) involves severe congenital hypotonia.5 XL-SMA patients have areflexia and often suffer congenital contractures that result from prenatal weakness and associated lack of movement. The weakness seen in these patients in progressive.
In SMA type 1, hypotonia tends to present in early childhood.6 Like those with SMA type 0 and XL-SMA, the hypotonia in SMA type 1 patients is also profound.7 It presents with symmetrical flaccid paralysis and is often associated with zero ability to move the head.
Innovation in neuroscience and genetics has enabled new diagnostic possibilities, including rapid molecular diagnosis of SMA and several other muscular disorders.8 Nonetheless, the hypotonia and weakness that is characteristic of SMA can also facilitate differential diagnosis. For instance, experts have suggested that SMA type 0 should be considered during the differential diagnosis of neonates with severe generalized hypotonia that is unexplained and accompanied by severe respiratory stress at birth, particularly when the patients appear alert.4,9 In SMA, the weakness tends to be symmetrical, observed more in the lower limbs than in the upper limbs, and seen more proximally than distally.7
In infants, weakness and hypotonia can signal a variety of conditions.10 In addition to neuromuscular disorders, weakness and hypotonia can be symptoms of a connective tissue disorder, metabolic disease, or just premature birth. SMA type 1 may be suspected in these infants if hypotonia is coupled with tongue fasciculations. In XL-SMA too, tongue fasciculations are present in infancy.5 However, unlike in SMA type 1, XL-SMA involves facial, ocular, and bulbar abnormalities. Thus, severe hypotonia coupled with dysmorphic features may suggest an XL-SMA diagnosis.11
In addition to physical examination and molecular diagnosis, electrodiagnostic studies can also help to identify SMA in those with infantile hypotonia.2 For instance, when needle eletromyography shows signs of denervation, infantile SMA is likely. Given the medical tools available, it should now be possible to identify SMA through a variety of means, but weakness and hypotonia are potentially the initial indications that one should consider an SMA diagnosis.
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