Andermann syndrome. Agenesis of corpus callosum with polyneuropathy.
Incidence
The syndrome is familial and is transmitted as an autosomal recessive trait. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada). Close to 250 cases have been identified.
Clinical Characteristics
Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder has been identified, it is on 15q13-q14, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. The first manifestations of the condition become apparent around age 4 months to 6 months with evidence of delayed motor milestones, hypotonia, areflexia, and muscular weakness, more marked distally and in the lower limbs. The great majority of patients started walking, most with support and braces, between 4 years and 8 years, but some have never walked by themselves. This is shortly followed by progressive motor deterioration with increased weakness, amyotrophy, and contractures of the distal musculature. Progressive scoliosis occurs between the ages of 9 years and 11 years. Most become confined to a wheelchair in early adolescence.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
The diagnosis of Andermann syndrome is confirmed by the unique association of distinct clinical features, especially in a population at risk, with the findings of partial or complete agenesis of the corpus callosum on CT or MRI examination. In addition, electrophysiological studies show evidence of a sensorimotor neuropathy with signs of denervation, absence of sensory action potentials, and reduction of motor nerve conduction velocity. Muscle biopsy reveals signs of neurogenic atrophy; sural nerve biopsies show a loss of large myelinated axons.