title: Macrocerebellum: significance and pathogenic considerations.
abstract: Macrocerebellum is a rare finding characterized by an abnormally large cerebellum. Only few patients with a syndromal or isolated macrocerebellum have been reported so far. This article aims to categorize the magnetic resonance imaging (MRI) findings, quantitate the macrocerebellum by volumetric analysis, characterize the neurological and dysmorphic features and cognitive outcome, and report the results of genetic analyses in children with macrocerebellum. All MR images were qualitatively evaluated for infratentorial and supratentorial abnormalities. Volumetric analysis was performed. Data about neurological and dysmorphic features, outcome, and genetic analysis were collected from clinical histories and follow-up examinations. Five patients were included. Volumetric analysis in three patients confirmed large cerebellar size compared to age-matched controls. MR evaluation showed that thickening of the cortical gray matter of the cerebellar hemispheres is responsible for the macrocerebellum. Additional infratentorial and supratentorial abnormalities were present in all patients. Muscular hypotonia, as well as impaired motor and cognitive development, was found in all patients, with ocular movement disorders in three of five patients. The five patients differed significantly in terms of dysmorphic features and involvement of extracerebral organs. Submicroscopic chromosomal aberrations were found in two patients. Macrocerebellum is caused by thickening of the cortical gray matter of the cerebellar hemispheres, suggesting that cerebellar granule cells may be involved in its development. Patients with macrocerebellum show highly heterogeneous neuroimaging, clinical, and genetic findings, suggesting that macrocerebellum is not a nosological entity, but instead represents the structural manifestation of a deeper, more basic biological disturbance common to heterogeneous disorders.
authors.affiliation: Department of Pediatric Neurology, University Children's Hospital of Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Poretti
authors.forename: Volker
authors.initials: V
authors.lastname: Mall
authors.forename: Martin
authors.initials: M
authors.lastname: Smitka
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grunt
authors.forename: Sarah
authors.initials: S
authors.lastname: Risen
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Toelle
authors.forename: Jane E
authors.initials: JE
authors.lastname: Benson
authors.forename: Shoko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Nikolai H
authors.initials: NH
authors.lastname: Jung
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Neuhann
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.forename: Maja
authors.initials: M
authors.lastname: Steinlin
authors.forename: Avner
authors.initials: A
authors.lastname: Meoded
authors.forename: Thierry A G M
authors.initials: TA
authors.lastname: Huisman
authors.forename: Eugen
authors.initials: E
authors.lastname: Boltshauser
mesh_terms: D001921:Brain / Q000473:pathology*; D002526:Cerebellar Diseases / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009123:Muscle Hypotonia / Q000473:pathology; D059906:Neuroimaging / Q000379:methods