Journal article
Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation.
- Romaniello R Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy.
- Arrigoni F Neuroimaging Laboratory, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
- Panzeri E Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
- Poretti A Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Micalizzi A Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
- Citterio A Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
- Bedeschi MF Clinical Genetics Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
- Berardinelli A Unit of Child Neurology and Psychiatry, IRCCS "C. Mondino" Foundation, Pavia, Italy.
- Cusmai R Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
- D'Arrigo S Developmental Neurology Division, IRCCS Fondazione Istituto Neurologico C. Besta, Milan, Italy.
- Ferraris A Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
- Hackenberg A Universitäts, Kinderspital Zürich, Eleonorenstiftung, Zürich, Switzerland.
- Kuechler A Institut für Humangenetik Essen, Universität Duisburg-Essen, Essen, Germany.
- Mancardi M Unit of Child Neuropsychiatry Giannina Gaslini Institute, Genoa, Italy.
- Nuovo S Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
- Oehl-Jaschkowitz B Practice of Human Genetics, Homburg (Saar), Germany.
- Rossi A Neuroradiology Unit, Giannina Gaslini Institute, Genoa, Italy.
- Signorini S Unit of Child Neurology and Psychiatry, IRCCS "C. Mondino" Foundation, Pavia, Italy.
- Tüttelmann F Institute of Human Genetics, University of Münster, Münster, Germany.
- Wahl D Private Practice for Human Genetics, Augsburg, Germany.
- Hehr U Department of Human Genetics, University of Regensburg, Regensburg, Germany.
- Boltshauser E Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
- Bassi MT Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
- Valente EM Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. enzamaria.valente@unipv.it.
- Borgatti R Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy. renato.borgatti@bp.lnf.it.
- 2017-07-06
Published in:
- European radiology. - 2017
Cerebellum
Dysplasia
Mutation
Neuroimaging
Tubulin genes
Adult
Brain Stem
Cerebellum
Child
Child, Preschool
Developmental Disabilities
Female
Humans
Infant
Magnetic Resonance Imaging
Male
Middle Aged
Mutation
Nervous System Malformations
Neuroimaging
Tubulin
Young Adult
English
OBJECTIVE
To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations.
METHODS
Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa.
RESULTS
Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected.
CONCLUSIONS
The cerebellar involvement in tubulinopathies shows specific features that may be labelled as 'tubulin-related CD'. This pattern is unique and differs from other genetic causes of cerebellar dysplasia.
KEY POINTS
• Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as 'tubulin-related CD'. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.
To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations.
METHODS
Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa.
RESULTS
Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected.
CONCLUSIONS
The cerebellar involvement in tubulinopathies shows specific features that may be labelled as 'tubulin-related CD'. This pattern is unique and differs from other genetic causes of cerebellar dysplasia.
KEY POINTS
• Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as 'tubulin-related CD'. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1007/s00330-017-4945-2
- PMID 28677066
- Persistent URL
- https://sonar.ch/global/documents/47661
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