SMA II (chronic spinal muscular atrophy; Dubowitz disease).
Incidence
Autosomal recessive inheritance.
Clinical Characteristics
SMA II (chronic spinal muscular atrophy; Dubowitz disease). SMA II manifests as onset usually between six and 12 months of age and eventual ability to sit independently when placed. Although poor muscle tone may be evident at birth or within the first few months of life, patients with SMA II may gain motor milestones slowly. Often concerns are not raised until a child is not sitting independently by age nine to 12 months or is not standing by age one year. Finger trembling and general flaccidity are common. Patients on average lose the ability to sit independently by the mid-teens. 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 II clinical characteristics: Onset of muscle weakness usually after six months of age. Finger trembling; almost invariably present. Low muscle tone (flaccidity). Absence of tendon reflexes in ~70% of individuals. 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 strongly 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.