Werdnig-Hoffmann disease is the most severe type of spinal muscular atrophy (SMA). Known as "infantile SMA," Werdnig-Hoffmann is a rare, inherited, autosomal recessive neuromuscular disease. Both parents unknowingly carry the gene for the disorder, and when the child inherits the defective gene from both parents, the disease develops. Approximately 1 in 50 people or 1 in 2,500 couples in the United States are carriers. When both parents carry the gene, the likelihood of the child inheriting the disease is one in four or a 25% chance with each pregnancy. Since the 1990s, prenatal and carrier testing have been made available to families.
Werdnig-Hoffmann is a disease of the anterior horn cells. These neurons, located in the spinal cord, are the main motor nerves that transmit nerve impulses from the spinal cord or brain to muscular or glandular tissue. Molecular genetic testing has shown that all types of autosomal recessive SMA are caused by mutations in the survival motor neuron (SMN) gene on chromosome 5. Deletion of the neuronal apoptosis inhibitory protein (NAIP) gene close to the SMN gene also is associated with SMA. More patients with Werdnig-Hoffmann disease than other type of SMA have NAIP deletions. Spinal muscular atrophy destroys nerves controlling voluntary muscle movement, affecting crawling, walking, head, neck control, and swallowing.
Classification of SMA subdivisions is based on age at symptoms onset rather than the genetic profile. There are five more common categories of SMA:
* SMA type 1, also called Werdnig-Hoffmann disease, is evident before birth or within the first 6 months of life. There may be reduced fetal movement in the final months of pregnancy. Symptoms include floppiness of the limbs and trunk, feeble movements of the arms and legs, swallowing and feeding difficulties, and impaired breathing. Infants with the gravest prognosis have problems sucking or swallowing. A twitching of the tongue often is seen. This is the most common and severe type of SMA. Affected children never sit or stand and usually die before the age of 2 years.
* SMA type 2 symptoms usually begin at the age of 7 to 18 months. Children may have respiratory problems, floppy limbs, decreased or absent deep tendon reflexes, and twitching of the arm, leg, or tongue muscles. These children may learn to sit but will never be able to stand or walk. Life expectancy varies.
* SMA type 3, also called Kugelberg-Welander disease, affects children 2 to 17 years of age. Symptoms include abnormal manner of walking; difficulty running, climbing steps, or rising from a chair; and slight tremor of the fingers.
* SMA type 4, also called Kennedy syndrome or progressive spinobulbar muscular atrophy, may occur at the age of 15 to 60 years. Features include weakness of muscles in the tongue and face, difficulty swallowing, speech impairment, and excessive development of the mammary glands in males. The course of the disorder usually is slowly progressive. Kennedy syndrome is an X-linked recessive disorder, which means that women carry the gene, but the disorder occurs only in men.
* Congenital SMA with arthrogryposis is a persistent contracture of joints with fixed abnormal posture of the limb. This extremely rare disorder manifests by severe contractures, curvature of the spine, chest deformity, respiratory problems, an unusually small jaw, and drooping upper eyelids.
The diagnosis of SMA is determined with three tests: a blood test for the gene responsible for the disorder (primary diagnostic test), electromyography, and muscle biopsy. Treatment involves symptomatic support of respiratory difficulties and infections, curvature of the spine, and muscle atrophy. Children may benefit from physical therapy, orthotic supports, rehabilitation, and mechanical devices to help them eat or speak. Most importantly, children with SMA have normal to high intelligence and should be encouraged to engage in typical activities of learning and development.