TY - JOUR
T1 - Ataxia, intellectual disability, and ocular apraxia with cerebellar cysts
T2 - A new disease?
AU - Poretti, Andrea
AU - Häusler, Martin
AU - Von Moers, Arpad
AU - Baumgartner, Bastian
AU - Zerres, Klaus
AU - Klein, Andrea
AU - Aiello, Chiara
AU - Moro, Francesca
AU - Zanni, Ginevra
AU - Santorelli, Filippo M.
AU - Huisman, Thierry A.G.M.
AU - Weis, Joachim
AU - Valente, Enza Maria
AU - Bertini, Enrico
AU - Boltshauser, Eugen
N1 - Funding Information:
Grant/Financial Support This work was partly supported by the Anna Müller Grocholski Foundation, Zurich, Switzerland (grant to AP), the European Research Council (ERC starting grant #260888 to EMV), and the Italian Ministry of Health (Ricerca Corrente 2013, Ricerca Finalizzata Malattie Rare 2008 to EMV).
PY - 2014/2
Y1 - 2014/2
N2 - Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP 6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger sequencing. Seven children from five families were studied. Ataxia, intellectual disability, and language impairment were found in all patients, ocular motor apraxia in five, and severe myopia in three. None of the patients had weakness, only three a minimally increased creatine kinase value. Qualitative neuroimaging evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres and vermis in all children. Additional findings were an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in five. The SNP array showed no pathogenetic imbalances in all children evaluated. In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical and neuroimaging findings in our patients highly suggests that this phenotype may represent a novel entity, possibly falling within the spectrum of dystroglycanopathies.
AB - Cerebellar cysts are rare findings in pediatric neuroimaging and rather characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim to report on seven children with cerebellar cysts showing absence of weakness and ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about neurological and ophthalmological features, outcome, and creatine kinase values were collected from clinical histories and follow-up examinations. All MR images were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP 6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger sequencing. Seven children from five families were studied. Ataxia, intellectual disability, and language impairment were found in all patients, ocular motor apraxia in five, and severe myopia in three. None of the patients had weakness, only three a minimally increased creatine kinase value. Qualitative neuroimaging evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres and vermis in all children. Additional findings were an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in five. The SNP array showed no pathogenetic imbalances in all children evaluated. In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical and neuroimaging findings in our patients highly suggests that this phenotype may represent a novel entity, possibly falling within the spectrum of dystroglycanopathies.
KW - Cerebellar cysts
KW - Cerebellum
KW - Congenital muscular dystrophy
KW - Dystroglycanopathy
KW - Neuroimaging
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U2 - 10.1007/s12311-013-0521-8
DO - 10.1007/s12311-013-0521-8
M3 - Article
C2 - 24013853
AN - SCOPUS:84896488858
SN - 1473-4222
VL - 13
SP - 79
EP - 88
JO - Cerebellum
JF - Cerebellum
IS - 1
ER -