Congenital Muscular Dystrophies (CMD) is an umbrella term that represents a group of inherited myopathies that present at birth or shortly after birth. They are mostly autosomal recessive disorders, and have wide variation in severity and progression. They are known as Dystroglycanopathies.
Genes involved in dystroglycanopathies glycosylate the protein alpha-dystroglycan. The alpha-dystroglycan protein anchors the cytoskeleton (the structural framework of the cell) to the the lattice of proteins and other molecules outside the cell. In muscle the anchoring function helps stabilize and protect muscle fibres. In the brain it helps neuronal migration.
These genetically heterogeneous diseases include a range of conditions with different degrees of severity. At the most severe end of the clinical spectrum, Walker-Warburg syndrome (WWS), muscle-eye-brain disease (MEB) and Fukuyama congenital muscular dystrophy (FCMD) are characterized by congenital muscular dystrophy and severe structural brain and eye abnormalities, which in WWS result in early infantile death. These typically present at birth or infancy.
At the mildest end of the clinical spectrum, affected individuals present with limb girdle muscular dystrophy (LGMD), without brain and eye involvement, and present in childhood or early adulthood
Typically, newborn babies with CMD present as floppy babies, commonly with arthrogryposis. There may also be ocular defects, seizures, developmental delay. Biopsy usually confirms the diagnosis and the prognosis, although there are genes that we are still unaware of that may go undetected.
On imaging there may be lissencephaly (type II), with a cobblestone like appearance that is typically seen in CMDs, such as: Walker-Warburg Syndrome, muscle-eye-brain disease, and Fukayama congenital muscular dystrophy. The cobblestoning will be most apparent anteriorly, and there may be less than normal sulcation in the brain, such as a small sylvian fissure. There may also be cerebellar hypoplasia (with or without cysts), myelination abnormalities, enlarged ventricles, and dysgenesis of the corpus callosum. Specifically, patients with Fukayama CMD may show diffuse central cerebral hypomyelination, cerebellar polymicrogyria with or without cysts, frontal polymicrogyria, and hypoplasia of the pons and cerebellar vermis. Patients with pure CMD showed diffuse cerebral hypomyelination with mild pontine and cerebellar hypoplasia, while patients with muscle-eye-brain disease had an absence of the septum pellucidum, diffuse cerebral cortical dysplasia, pontine and cerebellar vermian hypoplasia, patchy hypomyelination and variable callosal hypogenesis and hydrocephalus. Patients with Walker-Warburg syndrome had diffuse cerebral cobblestone cortex, absence of cerebral and cerebellar myelin, pontine and cerebellar vermal hypoplasia, hydrocephalus and variable callosal hypogenesis.
References
2. Barkovich A.J., Neuroimaging manifestations and classification of congenital muscular dystrophies. American Journal of Neuroradiology Sep 1998, 19 (8) 1389-1396;