title: Brain involvement in muscular dystrophies with defective dystroglycan glycosylation.
abstract: OBJECTIVE
  To assess the range and severity of brain involvement, as assessed by magnetic resonance imaging, in 27 patients with mutations in POMT1 (4), POMT2 (9), POMGnT1 (7), Fukutin (4), or LARGE (3), responsible for muscular dystrophies with abnormal glycosylation of dystroglycan (dystroglycanopathies).
  
  
  METHODS
  Blinded review of magnetic resonance imaging brain scans from 27 patients with mutations in 1 of these 5 genes.
  
  
  RESULTS
  Brain magnetic resonance images were normal in 3 of 27 patients; in another 5, only nonspecific abnormalities (ventricular dilatation, periventricular white matter abnormalities, or both) were seen. The remaining 19 patients had a spectrum of structural defects, ranging from complete lissencephaly in patients with Walker-Warburg syndrome to isolated cerebellar involvement. Cerebellar cysts and/or dysplasia and hypoplasia were the predominant features in four patients. Polymicrogyria (11/27) was more severe in the frontoparietal regions in 6, and had an occipitofrontal gradient in 2. Pontine clefts, with an unusual appearance to the corticospinal tracts, were seen in five patients with a muscle-eye-brain-like phenotype, three patients with POMGnT1, one with LARGE, and one with POMT2 mutations. Prominent cerebellar cysts were always seen with POMGnT1 mutations, but rarely seen in POMT1 and POMT2. Brainstem and pontine abnormalities were common in patients with POMT2, POMGnT1, and LARGE mutations.
  
  
  CONCLUSIONS
  Our results expand the spectrum of brain involvement associated with mutations in LARGE, POMGnT1, POMT1, and POMT2. Pontine clefts were visible in some dystroglycanopathy patients. Infratentorial structures were often affected in isolation, highlighting their susceptibility to involvement in these conditions.
authors.affiliation: Dubowitz Neuromuscular Unit, Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Clement
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Caroline
authors.initials: C
authors.lastname: Godfrey
authors.forename: Janine
authors.initials: J
authors.lastname: Smith
authors.forename: Stephanie
authors.initials: S
authors.lastname: Robb
authors.forename: Maria
authors.initials: M
authors.lastname: Kinali
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Adnan
authors.initials: A
authors.lastname: Manzur
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Frances
authors.initials: F
authors.lastname: Cowan
authors.forename: Ros
authors.initials: R
authors.lastname: Quinlivan
authors.forename: Andrea
authors.initials: A
authors.lastname: Klein
authors.forename: Cheryl
authors.initials: C
authors.lastname: Longman
authors.forename: Robert
authors.initials: R
authors.lastname: McWilliam
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Rachael
authors.initials: R
authors.lastname: Mein
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.forename: Kathryn
authors.initials: K
authors.lastname: North
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
authors.forename: Mary
authors.initials: M
authors.lastname: Rutherford
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D049030:Dystroglycans / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008364:Mannosyltransferases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009136:Muscular Dystrophies / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D009421:Nervous System Malformations / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype
chemical_list: C113587:FKTN protein, human; D008565:Membrane Proteins; D049030:Dystroglycans; C117674:LARGE1 protein, human; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase