Spinal Muscular Atrophy I (Werdnig-Hoffman Disease)
The majority of cases of SMA I present within the first two months, with generalized hypotonia and symmetrical weakness. The age of onset of symptoms is less than 4 months in the vast majority of cases.
Weak sucking, dysphagia, labored breathing during feeding, frequent aspiration of food or secretions, and weak cry are frequently noted by history.Examination shows generalized hypotonia and symmetric weakness involving the lower extremities earlier and, to a greater extent, in the upper extremities. Proximal muscles are weaker than distal extremities. In the supine position, the lower extremities may be abducted and externally rotated in a “frog-leg” position. The upper extremities tend to be adducted and externally rotated at the shoulders with a semiflexed elbow. Volitional movements of fingers and hands persist well past the time when the shoulders and elbows cannot be flexed against gravity. The thorax is flattened anteroposteriorly and bell-shaped as a result of intercostal weakness. Pectus excavatum may be variably present. The diaphragm is usually preserved, relative to the intercostal and abdominal musculature. This results in a diaphragmatic breathing pattern during respiration with abdominal protrusion, paradoxical thoracic depression, and intercostal retraction. Neck flexor weakness may result in persistent posterior head lag when the trunk is lifted forward from the supine position. Neck extensor weakness may result in forward head lag when the infant is positioned in the horizontal prone position. With advanced disease, the mouth may remain open as a result of masticatory muscle weakness. Facial weakness may be noted in up to half of patients. The diagnostic criteria for SMA outlined by the International SMA Consortium (97) lists marked facial weakness as an exclusionary criterion for SMA, but this is not an absolute criterion. Tongue fasciculations have been reported in 56% to 61% of patients (113), so the absence of this finding does not necessarily exclude the disease. In one series (113), deep tendon reflexes (DTRs) were absent in all four extremities in 74% of cases. Thus, the preservation of DTRs does not exclude the diagnosis of SMA. Appendicular muscle fasciculations and distal tremor are also associated examination findings. Extraocular muscles are spared, as is the myocardium. Mild to moderate hip flexion, knee flexion, and elbow flexion contractures may be observed in some patients, along with wrist contractures and ulnar drift of the fingers. Severe arthrogryposis is not typically observed.
Diagnosis is confirmed by a consideration of clinical findings, molecular genetic studies, and, occasionally, electrodiagnostic studies. Muscle biopsy is generally not required to confirm the diagnosis.
In a large series from Germany (98), 197 patients classified as type I (never sits alone) had the following survival probabilities: 32% at age 2; 18% at age 4; 8% at age 10; and 0% at age 20.