CONGENITAL MUSCULAR DYSTROPHIES WITH STRUCTURAL BRAIN INVOLVEMENT: THE ROLE OF BRAIN MRI

Objective: To review the recent advances in congenital muscular dystrophies with brain involvement.

Background: MRI has become an important tool in diagnosing complex congenital muscular dystrophies (CMD) with brain abnormalities. The currently recognized two major groups of CMDs with MRI brain abnormalities are 1/ laminin α2 deficient CMD (MDC1A) with mutations in the LAMA2 gene and 2/ a group of CMDs with deficient α-dystroglycan due to its abnormal glycosylation. The MRI in MDC1A shows diffusely abnormal white matter and very rare cortical abnormalities while in the latter group of CMDs, there is a whole spectrum of abnormalities involving both white and grey matter. At least five major phenotypes are recognized in the latter group. From the most severe to the mildest they are: Walker-Warburg syndrome (WWS), muscle-eye-brain disease (MEB), Fukuyama CMD (FCMD) and CMD Type 1C and 1D (MDC1C and MDC1D).

The most severe MRI abnormalities are found in WWS. They include migrational defects with Type II lissencephaly (cobblestone type), hydrocephalus, vermal or general cerebellar hypoplasia, flat brain stem with small pyramids and abnormal white matter. Additional abnormalities such as hypoplasia/agenesis of corpus callosum, fused hemispheres, cerebellar cysts, occipital encephalocele and Dandy-Walker variant can be also found. MRI in children with MEB, FCMD and MDC1C also show a spectrum of grey and white matter abnormalities which in general are less prominent than those seen in WWS. The rare cases of MDC1D show only subtle MRI changes. There may be an overlap in these complex CMDs, both genotypically and also in MRI findings.

Conclusion: Characteristic brain MRI changes should lead the clinician to the proper diagnosis of CMD with brain and eye abnormalities. Furthermore, the different MRI abnormalities help to classify the individual types of CMD.

Keywords: α-dystroglycan, CMD with brain and eye findings, laminin α2