Spinal Muscular Atrophy and Spinal Bulbar Muscular Atrophy

Spinal Muscular Atrophy Type I (Werdnig-Hoffmann Disease). In the healthy newborn infant, the purposeless movements of the extremities are associated with a well-defined muscular tone, despite the lack of coordinated motor function. In addition, the fullterm newborn has a well-developed suck and swallow. Most infants with SMA type I demonstrate normal muscular tone, motor function, and bulbar function at birth. However, within the first few weeks to months postbirth, they develop generalized hypotonia and weakness. In addition, they manifest a respiratory pattern characterized by paradoxic chest and abdomen movement that results from the selective weakness of intercostal muscles in the setting of preserved diaphragm function. Without supportive treatment, infants subsequently develop the characteristic bellshaped deformity of the thorax. In addition, they manifest a hypotonic posture characterized by abducted hips and internal rotation of the forearms (frog-legged and jug-handle habitus). Progressive bulbar and respiratory insufficiency results in a vulnerability to both aspiration and infectious pneumonias. Extraocular movements and facial movement are preserved until late. Careful evaluation of the tongue reveals evident tongue fasciculations. In contrast to adults, fasciculations in limbs are difficult to appreciate due to excessive subcutaneous fat in infants. In milder cases, normal motor milestones, such as head control and ability to roll and sit, are simply not acquired as expected during the first few months. Ultimately, however, SMA type I is defined clinically by the inability of all such infants to achieve independent sitting. In a subset of the most severe cases, reduced fetal movement occurs before birth, and the infant is born with generalized hypotonia, neuromuscular weakness, respiratory insufficiency, bulbar dysfunction, and proximal joint contractures.

Spinal muscular atrophy is a hereditary illness, most often of autosomal recessive inheritance, although other variant forms exist, including X-linked and dominant forms. The most common form of SMA is the proximal recessive type, which includes a broad range of subtypes ranging from the severe infantile variant (depicted here) to ambulatory forms with adult-onset.

Electromyography as a primary diagnostic tool has been largely replaced by genetic testing in most cases because more than 95% of such infants have a homozygous deletion/mutation of exon 7 of the survival motor neuron 1 gene (SMN1 gene). Once significant weakness is manifest, the EMG findings are distinct in type I, demonstrating diffuse fibrillations in virtually all muscles in association with markedly reduced recruitment of small motor units in the absence of the typical large complex motor units characteristic of reinnervation in milder, more chronic forms of the disorder. Muscle biopsy shows findings typical of neurogenic atrophy. Other lesions in the motor unit can mimic Werdnig-Hoffmann disease but, as a rule, can be differentiated by clinical and electromyographic findings and examination of muscle biopsy specimens if genetic and/or neurophysiologic testing is not definitive. Differential diagnosis for presentation in infancy includes spinal muscular atrophy with respiratory distress (SMARD), which is distinguished by early respiratory failure due to diaphragm involvement, especially in association with more distal presentation of limb weakness. X-linked SMA manifests as a severe infantile SMA variant predominantly affecting males. Diseases of the neuromuscular junction, such as transient neonatal myasthenia gravis and infantile botulism, and rare recessive inherited peripheral neuropathy variants, such as congenital hypomyelinating neuropathy, should be considered in the differential diagnosis. Treatment for Werdnig-Hoffmann disease remains largely supportive. The prognosis is generally poor, with onset is in the neonatal period. Many of these infants do not survive until their first birthday. However, even in the absence of extensive supportive care, historically, up to 30% of infants with SMA type I survive beyond 2 years of age, some into adolescence or beyond.

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