What are the signs and symptoms of LARGE congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Mutations in the LARGE gene are the rarest cause of CMD with defect of α-dystroglycan glycosylation. One case has been described in a 17-year-old female adolescent who presented with weakness and hypotonia at age 5 months. She had profound mental retardation and an MRI that showed mild white-matter abnormalities and structural malformations suggestive of aberrant neuronal migration. An abnormal electroretinogram suggested eye abnormalities.

Two sisters of first cousin parents had a similar course. Presentation was in the first year of life with hypotonia and delayed motor and cognitive milestones. They walked at 2 years, but with difficulty and muscle hypertrophy was noted. Mental retardation was present. Only mild eye abnormalities were noted, but severe abnormalities on brain MRI were seen including ventricular dilatation, cerebellar hypoplasia, high signal periventricular and deep white matter abnormalities, and in the more affected sibling pachygyria of the frontal lobes. [27]

Two siblings with consanguineous parents had a phenotype similar to Walker-Warburg syndrome with presentation at birth with severe hypotonia and respiratory difficulty. CKs were markedly elevated. Both patients died within 6 months. Both had eye abnormalities and brain imaging showing severe hydrocephalus and structural brain disease. [28]

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