Spinal Muscular Atrophy I (Werdnig-Hoffmann 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 (166) list 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 (180), so the absence of this finding does not necessarily exclude the disease. In one series (180), 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 are 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 (167), 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.
Spinal Muscular Atrophy II
Spinal muscular atrophy II disease onset is usually more insidious than that of SMA I. The findings of generalized hypotonia, symmetrical weakness, and delayed motor milestones are hallmarks of SMA II. Weakness also involves proximal muscles more than distal muscles, and lower extremity more than upper extremity. A fine tremor of the fingers and hands occurs in a minority of patients. This "polyminimyoclonus" may be attributed to spontaneous, repetitive rhythmical discharges by the motor neurons that innervate a large territory of muscle. Wasting tends to be more conspicuous in SMA II versus SMA I. DTRs are depressed and usually absent in the lower extremities. Appendicular or thoracic muscle wall fasciculations may be observed. Tongue fasciculations have been observed in 30% to 70% of SMA II patients (166,180,181). Progressive kyphoscoliosis and neuromuscular restrictive lung disease are almost invariably seen in the late first decade. Contractures of the hip flexors, tensor fasciae latae, hamstrings, triceps surae, and elbow and finger flexors are quite common. Hypotonic hip dislocations have been noted commonly in SMA II patients. Sensory examination is completely normal and extraocular muscles and the myocardium are spared. In a large series from Germany (167), of 104 cases classified as SMA II (sits alone, never walks), 98% survived to the age of 10 and 77% to the age of 20. Thus, a longer life span is possible with adequate supportive care.
SMA II is a slowly progressive condition affecting proximal musculature more than distal. The calculated grade of progression for SMA may be less than one-half manual muscle testing units decline per decade (86). Longitudinal series of 12 to 39 months' duration have shown essentially stable strength measurements but slow loss of function (182,183).
Pathologic changes on muscle biopsy have been consistent with hypotrophic change in fetal muscle development. Other changes are consistent with a more active denervating process. Thus, SMA includes a component of myofiber atrophy, comparable to that seen in other denervating diseases and is not a pure hypotrophic process occurring during early fetal development.
