Dystroglycanopathies are a group of muscular dystrophies that are due to hypoglycosylation of the alpha-dystroglycan protein, an important cell adhesion molecule involved in the binding of extracellular matrix proteins to surroundings. Individuals affected by dystroglycanopathies have a very variable spectrum of symptoms ranging from severe types present at birth, to relatively mild adult onset forms. These disorders are caused by mutations in any one of a number of different genes, although the nature of the mutation does not always correlate with the severity of symptoms. For this reason, dystroglycanopathies may be difficult to diagnose. Dr. Francesco Muntoni and colleagues at the Institute of Child Health in London have reported the findings of a recent study aimed to investigate how the brain was affected in individuals with dystroglycanopathies. Magnetic Resonance Imaging (MRI) brain scans were carried out on 27 individuals affected by dystroglycanopathies. These included those with congenital muscular dystrophies (CMD), which are conditions where the symptoms range in severity from the extremely severe Walker-Warburg Syndrome (WWS), to much milder forms of the condition. Some patients with limb-girdle muscular dystrophy were also included. All patients had mutations in one of five genes known to cause dystroglycanopathies. These genes were POMT1, POMT2, POMGnT1, Fukutin and LARGE. It was found that that the extent of central nervous system involvement caused by each of these genetic defects is much more variable from person to person than originally described. Patients with mutations in the Fukutin gene had a very variable level of brain involvement, while patients with POMT1, POMGnT1 and LARGE mutations showed a narrower range of variability. POMT2 mutations were originally believed to cause either the severe brain abnormalities seen in WWS or cerebellar hypoplasia. However, this study showed that a much wider range of brain abnormality could occur as a result of mutations in this gene. The results of this study should give a better insight into the spectrum of brain changes seen in this complex group of disorders. This study should hopefully facilitate the diagnosis of this group of disorders and in some cases may help to direct genetic testing, enabling faster and more accurate diagnosis.

Références : Ann Neurol. 2008 Nov;64(5):573-82.
Clement E. et al. Brain involvement in muscular dystrophies with defective dystroglycan glycosylation.