The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD) and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia. DMD boys have a lower IQ (average 85) than normal. The degree of cognitive impairment may be associated with a mutation in the dystrophin isoform, Dp71. Brain histology shows abnormalities in dendrites and loss of neurones, and biochemical changes are indicative of CNS pathology, including an increase in levels of choline-containing compounds. Studies in the mdx mouse have shown a disruption of GABA receptors, that may impact on the action of certain drugs, sleep disorders, and motor control in DMD. Biochemical lesions are particularly prominent in the cerebellum and hippocampus, regions involved in learning disabilities, especially dyslexia and verbal memory deficits. EEG studies have shown a higher proportion of abnormalities in DMD than normal subjects, although many have lacked adequate controls. A reduction in motor cortex excitability, measured by transcranial magnetic stimulation, is attributed to an aberrant synaptic functioning. [1]

COMMENT. Duchenne muscular dystrophy, an X-linked inherited disease affecting 1 in 3300 live male births, is caused by the mutation of the dystrophin gene. The dystrophin protein is found in skeletal muscle and also in the CNS. The role of dystrophin and its absence or disruption in the CNS are significant in relation to the management and education of DMD patients. In addition to muscular weakness, and cognitive and learning disabilities, children with DMD have problems in motor control that may be partially attributed to CNS pathology. From a clinical standpoint, a Babinski response, a not infrequent finding in DMD, should not be interpreted as a pseudo sign due to muscle weakness and imbalance.