Arthrogryposis multiplex congenita-spinal muscular atrophy (AMC-SMA association)
Incidence
Autosomic recessive inheritance.
Clinical Characteristics
AMC-SMA association (arthrogryposis multiplex congenita-spinal muscular atrophy). AMC-SMA manifests as severe weakness of prenatal onset and AMC (i.e., congenital joint contractures involving at least two regions of the body). Decreased fetal movement, polyhydramnios, and breech presentation are common. Typically the infants have absence of movement except for extraocular and facial movement. Death usually occurs from respiratory failure before one month of age. However, one report describes a child who is not ventilator-dependent at five years of age. 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 is characterized by muscle weakness and atrophy resulting from progressive degeneration and loss of the anterior horn (i.e., lower motor neuron) cells in the spinal cord and sometimes in the brainstem nuclei. The onset of weakness ranges from before birth to adolescence or young adulthood. The weakness is symmetric and progressive. Before the advent of molecular diagnosis, attempts were made to classify SMA into discrete subtypes; however, it is now apparent that the phenotype of SMA associated with disease-causing mutations of the SMN gene spans a continuum without clear delineation of subtypes. Nonetheless, the existing classification system based on age of onset is useful for prognosis and management.
Precipitants
none
Provocation Tests
none
Diagnostic Procedures
DB-W. It is suspected clinically. 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.