SMA III (juvenile spinal muscular atrophy; Kugelberg-Welander disease).
Incidence
Autosomic recessive inheritance.
Clinical Characteristics
SMA III (juvenile spinal muscular atrophy; Kugelberg-Welander disease). SMA III manifests after one year of age. Patients with SMA III walk independently but may fall frequently or have trouble walking up and down stairs at age two to three years. The legs are more severely affected than the arms. Prognosis generally correlates with the maximum motor function attained. Patients with SMA III who have never climbed stairs without using a rail lose walking ability by the mid-teens. Patients who develop normal walking skills prior to the onset of weakness can maintain this ability until the third or fourth decade of life. Diagnosis: The diagnosis of spinal muscular atrophy (SMA) is established in individuals with evidence of degeneration and loss of anterior horn cells (i.e., lower motor neurons) in the spinal cord and brainstem. Diagnostic criteria vary by age of onset. SMA III clinical characteristics: Weakness manifest as frequent falls or trouble walking up and down stairs at age two years to three years. Proximal limb weakness; the legs more severely affected than the arms. Testing used in the past to establish the diagnosis of SMA currently has little role in the diagnosis of most patients and is used primarily if molecular genetic testing of the SMN1 gene is normal. These tests include: Electromyography (EMG). EMG reveals denervation and diminished motor action potential amplitude. The EMG shows regular spontaneous motor unit activity, a unique feature in SMA. This is seen most commonly in SMA I/and occasionally in SMA II, but not in SMA III. A reduced interference pattern is seen with maximal effort; polyphasic waves, positive sharp waves, and fibrillations are present in all patients with SMA. Nerve conduction velocities (NCV). Motor and sensory NCVs are normal.
Precipitants
none
Provocation Tests
none
Diagnostic Procedures
DB-W. It is clinically suspected. Testing used in the past to establish the diagnosis of SMA currently has little role in the diagnosis of most patients and is used primarily if molecular genetic testing of the SMN1 gene is normal. These tests include: Electromyography (EMG). EMG reveals denervation and diminished motor action potential amplitude. The EMG shows regular spontaneous motor unit activity, a unique feature in SMA. This is seen most commonly in SMA I/and occasionally in SMA II, but not in SMA III. A reduced interference pattern is seen with maximal effort; polyphasic waves, positive sharp waves, and fibrillations are present in all patients with SMA. Nerve conduction velocities (NCV). Motor and sensory NCVs are normal. Molecular Genetic Testing: SMN1 mutation analysis: Mutation analysis is used to detect deletion of exons 7 and 8 of SMN1. Approximately 95-98% of individuals with a clinical diagnosis of SMA lack exon 7 in both copies of SMN1 (i.e., they are homozygous). Approximately 2-5% of patients with a clinical diagnosis of SMA are compound heterozygotes for deletion of SMN1 exon 7 and an intragenic mutation of SMN1.
Other analysis method used is the SMN1 sequence analysis: Sequence analysis may be used to identify the intragenic SMN1 mutations present in the 2-5% of patients who are compound heterozygotes. Linkage analysis is available for families in which direct DNA testing (Mutation analysis and/or sequence analysis) is not informative. Genetic analysis is available on a clinical basis. For detailed information on these tests, please contact genetests.org.
Muscle biopsy is generally not indicated if genetic DNA testing is available.