Congenital muscular dystrophies (central nervous system manifestations)
Congenital muscular dystrophies 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.
There is a wide spectrum of clinical manifestations in the different types of congenital muscular dystrophies, 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
- poor vision
Congenital muscular dystrophies 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.
- mutations in molecules with roles in cell migration and connection or proteins involved in their processing, such as α-dystroglycan (a part of the dystrophin-glycoprotein complex) or its ligand, merosin/laminin α2
- autosomal recessive
- muscle biopsy: mild to moderate dystrophic changes, +/- inflammatory infiltrate, +/- absent staining laminin α2
- 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
The latter types, CMD 2-4, belong to the group of dystroglycanopathies, which frequently have brain involvement.
Described features in general include:
- cobblestone lissencephaly
- myelination defects
- Z-shaped/kinked, hypoplastic brainstem
- hypoplastic vermis
- dysgenesis of the corpus callosum
History and etymology
The condition was first described by the English neurologist Frederick Eustace Batten (1865-1918) in his publications in 1903 and 1904 5,6.
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- 4. Bönnemann CG, Wang CH, Quijano-Roy S et-al. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul. Disord. 2014;24 (4): 289-311. doi:10.1016/j.nmd.2013.12.011 - Pubmed citation
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- 6. Reed UC. Congenital muscular dystrophy. Part II: a review of pathogenesis and therapeutic perspectives. Arq Neuropsiquiatr. 2010;67 (2A): 343-62. Pubmed citation
- 7. Angelini C, Pinzan E. Advances in imaging of brain abnormalities in neuromuscular disease. (2019) Therapeutic advances in neurological disorders. 12: 1756286419845567. doi:10.1177/1756286419845567 - Pubmed