Congenital muscular dystrophies (central nervous system manifestations)

Congenital muscular dystrophies (CMD.s) are a heterogeneous group of autosomal recessive myopathies presenting at birth with hypotonia, delayed motor development, and early onset of progressive muscle weakness, confirmed with a dystrophic pattern on muscle biopsy. 

Clinical presentation

There is a large spectrum of clinical manifestations in the different types of CMDs: from a severe and often early fatal infant syndrome with feeding and respiratory troubles to a moderate motor delay and mild or moderate limb-girdle involvement during childhood compatible with survival into adult life ^3,5. Common symptoms are:

• hypotonia (floppy baby)
• developmental delay
• seizures
• poor vision

CMDs are diagnosed by the analysis of the clinical severity and progression and confirmed by a muscle biopsy showing the presence of a dystrophic process without histological evidence of another neuromuscular disease ^4,5. 

Pathology

• mutations in molecules (merosin: laminin- α2) with roles in cell migration and connection
• autosomal recessive
• muscle biopsy: mild to moderate dystrophic changes, +/- inflammatory infiltrate, +/- absent staining laminin- α2

Classification

• CMD 1: abnormal white matter varies from mild (CMD1 merosin positive) to moderate-severe (CMD 1 merosin negative)
• CMD 2: Fukuyama congenital muscular dystrophy (FCMD), moderate dysplasia of cerebral neocortex and cerebellum, abnormal white matter
• CMD 3: Santavuori muscle-eye-brain (MEB) Finnish-type, less severe than CMD 4, with ventriculomegaly, vermian hypogenesis, dysplastic cortex, patchy abnormal white matter +/- callosal dysgenesis
• CMD 4: Walker-Warburg syndrome, most severe , with cobblestone brain, massive ventriculomegaly with absent/abnormal callosum, no myelin, kinked pons midbrain, vermian hypoplasia +/- cephalocele

Radiographic features

Described features in general include:

• cobblestone brain
• myelination defects
• Z-shaped brainstem/hypoplastic vermis
• ventriculomegaly
• callosal agenesis/hypogenesisdysgenesis of the corpus callosum

History and etymology

The condition was firstly described by the English neurologist Frederick Eustace Batten (1865-1918) in his publications in 1903 and 1904 ^5-6.