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POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease
  1. C Diesen1,
  2. A Saarinen1,
  3. H Pihko2,
  4. C Rosenlew1,
  5. B Cormand3,
  6. W B Dobyns4,
  7. J Dieguez1,
  8. L Valanne5,
  9. T Joensuu1,
  10. A-E Lehesjoki1
  1. 1Folkhälsan Institute of Genetics, Department of Medical Genetics and Neuroscience Centre, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
  2. 2Department of Paediatric Neurology, University of Helsinki
  3. 3Department of Genetics, Faculty of Biology, University of Barcelona, Barcelona, Spain
  4. 4Departments of Human Genetics, Neurology and Pediatrics, University of Chicago, Chicago, Illinois, USA
  5. 5Department of Radiology, University of Helsinki
  1. Correspondence to:
 Dr Anna-Elina Lehesjoki
 Folkhälsan Institute of Genetics, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland;

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Muscle-eye-brain disease (MEB; OMIM 253280) was first described in 1977 in Finland,1 where it is enriched because of founder effect and genetic isolation.2 MEB is now known to occur throughout the world, but Finland remains the country with the largest group of MEB patients.

MEB patients present as floppy infants with visual problems and severe mental retardation. The hypotonia is partly caused by muscular dystrophy and partly by cerebral dysfunction. Hypotonia is replaced by spasticity and contractures with increasing age.1,3 Visual failure is the result of progressive myopia, retinal degeneration, and congenital glaucoma. Juvenile cataracts develop by the age of 10 years. The presence of giant visual evoked potentials is an important diagnostic feature.4 The typical central nervous system malformation revealed by magnetic resonance imaging (MRI), referred to as “cobblestone complex”,5 consists of cobblestone cortex, midline deformities, flat brain stem, mild cerebellar hypoplasia, and cerebellar cortical cysts.6 Microscopically the cortex is disorganised, with an overgrowth of glia forming a thick membrane on the brain surface.7

The combination of muscular dystrophy and a severe neuronal migration defect is not exclusive for MEB, but is also seen in Walker–Warburg syndrome (WWS; OMIM 2366708) and Fukuyama congenital muscular dystrophy (FCMD; OMIM 2538009). The recent molecular genetic findings have provided an explanation as to why the distinct clinical features are partially shared in these three diseases. The MEB gene encodes a protein O-mannose b-1, 2-N-acetylglucosaminyltransferase (POMGnT1).10 Mutations in another enzyme involved in O-mannosylation, the O-mannosyltransferase (POMT1), were recently found in a group of WWS patients.11 Fukutin, encoded by the FCMD gene,12 is strongly suspected to play a role in glycosylation.13 The unifying feature in all these disorders is deficient post-translational glycosylation of α-dystroglycan,11,14–

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  • Conflicts of interest: none declared

  • C Diesen and A Saarinen made an equal contribution to this work