Clinical manifestations of Werdnig-Hoffmann disease (SMA 1) The most frequent form of these spinal muscular atrophies, the severe infantile type, is a common disease, occurring once in every 20,000 live births. After cystic fibrosis, it is also the most frequent cause of death from a recessively inherited disease. Characteristically the infant, usually born normally, is noted from birth to be unnaturally weak and limp (“floppy”). Some mothers report that fetal movement in utero had been less than expected or lacking altogether. In severe cases, arthrogryposis at the ankles and wrists or dislocation of the hips is noted at birth (arthrogryposis and its differential diagnosis is discussed in Chap. 45 in the section on the congenital neuromuscular disorders). The muscle weakness in these children is generalized from the beginning, and death comes early, usually within the first year. Other infants seem to develop normally for several months before the weakness becomes apparent. In these, the trunk, pelvic, and shoulder-girdle muscles are at first disproportionately affected, while the fingers and hands, toes and feet, and cranial muscles retain mobility. Hypotonia accompanies the weakness, and because passive displacement of articulated parts in testing muscle tone is easier to judge than power of contraction at this early age, it may be singled out as the dominant clinical characteristic. As a rule, the tendon reflexes are unobtainable. Volume of muscle is diminished but is difficult to evaluate in the infant because of the coverings of adipose tissue. Fasciculations are seldom visible except sometimes in the tongue. Perception of tactile and painful stimuli is undiminished, and emotional and social development measures up to age.
As the months pass, the weakness and hypotonia progress gradually and spread to all the skeletal muscles except the ocular ones. Intercostal paralysis with a degree of collapse of the chest is the rule. Respiratory movements become paradoxical (abdominal protrusion with chest retraction). The cry becomes feeble, and sucking and swallowing are less efficient. Such infants are unable to sit unless propped, and they cannot hold up their heads without support and cannot roll over or support their weight when placed on their feet. Their posture is characteristic: arms abducted and flexed at the elbow, legs in the “frog position” with external rotation and abduction at hips and flexion at hips and knees. If the effects of gravity are removed, all muscles continue to contract; that is there is paresis, not paralysis. Until late in the illness, these children appear bright-eyed, alert, and responsive.
Infants in whom the disease becomes apparent only after several months of life have a less-rapid decline than those affected in utero or at birth. Some of the former become able to sit and creep and even to walk with support; those with later onset may survive for several years and even into adolescence or early adult life, as already mentioned.
Laboratory data of confirmatory value are few. Muscle enzymes in the serum are usually normal or rarely elevated. The EMG, if performed at a late enough stage of development, displays fibrillations, proving the denervative basis of the weakness. Motor unit potentials are diminished in number and, in the more slowly evolving cases, some are larger than normal (giant or polyphasic potentials reflecting reinnervation). Motor nerve conduction velocities are normal or fall in the low-normal range (these are normally slower in infants than in adults). Electrophysiologic studies performed in the first few months of life may give ambiguous results.