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Brain involvement in muscular dystrophies with defective dystroglycan glycosylation
Author(s) -
Clement Emma,
Mercuri Eugenio,
Godfrey Caroline,
Smith Janine,
Robb Stephanie,
Kinali Maria,
Straub Volker,
Bushby Kate,
Manzur Adnan,
Talim Beril,
Cowan Frances,
Quinlivan Ros,
Klein Andrea,
Longman Cheryl,
McWilliam Robert,
Topaloglu Haluk,
Mein Rachael,
Abbs Stephen,
North Kathryn,
Barkovich A. James,
Rutherford Mary,
Muntoni Francesco
Publication year - 2008
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21482
Subject(s) - polymicrogyria , congenital muscular dystrophy , dystroglycan , hypoplasia , magnetic resonance imaging , lissencephaly , cortical dysplasia , pathology , cerebellar hypoplasia (non human) , medicine , anatomy , cerebellum , muscular dystrophy , biology , genetics , radiology , laminin , gene , cell
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. Interpretation 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. Ann Neurol 2008;64:573–582