. 2017 Dec;27(12):5080-5092.

doi: 10.1007/s00330-017-4945-2. Epub 2017 Jul 4.

Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation

Romina Romaniello¹, Filippo Arrigoni², Elena Panzeri³, Andrea Poretti^{4

5}, Alessia Micalizzi^{6

7}, Andrea Citterio³, Maria Francesca Bedeschi⁸, Angela Berardinelli⁹, Raffaella Cusmai¹⁰, Stefano D'Arrigo¹¹, Alessandro Ferraris¹², Annette Hackenberg¹³, Alma Kuechler¹⁴, Margherita Mancardi¹⁵, Sara Nuovo^{6

16}, Barbara Oehl-Jaschkowitz¹⁷, Andrea Rossi¹⁸, Sabrina Signorini⁹, Frank Tüttelmann¹⁹, Dagmar Wahl²⁰, Ute Hehr²¹, Eugen Boltshauser²², Maria Teresa Bassi³, Enza Maria Valente^{23

24}, Renato Borgatti²⁵

Affiliations

¹ Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy.
² Neuroimaging Laboratory, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
³ Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
⁴ 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.
⁵ Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
⁶ Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
⁷ Department of Biological and Environmental Sciences, University of Messina, Messina, Italy.
⁸ Clinical Genetics Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
⁹ Unit of Child Neurology and Psychiatry, IRCCS "C. Mondino" Foundation, Pavia, Italy.
¹⁰ Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
¹¹ Developmental Neurology Division, IRCCS Fondazione Istituto Neurologico C. Besta, Milan, Italy.
¹² Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
¹³ Universitäts, Kinderspital Zürich, Eleonorenstiftung, Zürich, Switzerland.
¹⁴ Institut für Humangenetik Essen, Universität Duisburg-Essen, Essen, Germany.
¹⁵ Unit of Child Neuropsychiatry Giannina Gaslini Institute, Genoa, Italy.
¹⁶ Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
¹⁷ Practice of Human Genetics, Homburg (Saar), Germany.
¹⁸ Neuroradiology Unit, Giannina Gaslini Institute, Genoa, Italy.
¹⁹ Institute of Human Genetics, University of Münster, Münster, Germany.
²⁰ Private Practice for Human Genetics, Augsburg, Germany.
²¹ Department of Human Genetics, University of Regensburg, Regensburg, Germany.
²² Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
²³ Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. enzamaria.valente@unipv.it.
²⁴ Department of Molecular Medicine, University of Pavia, Pavia, Italy. enzamaria.valente@unipv.it.
²⁵ Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy. renato.borgatti@bp.lnf.it.

PMID: 28677066
DOI: 10.1007/s00330-017-4945-2

Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation

Romina Romaniello et al. Eur Radiol. 2017 Dec.

. 2017 Dec;27(12):5080-5092.

doi: 10.1007/s00330-017-4945-2. Epub 2017 Jul 4.

Authors

Affiliations

¹ Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy.
² Neuroimaging Laboratory, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
³ Laboratory of Molecular Biology, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
⁴ 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.
⁵ Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
⁶ Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
⁷ Department of Biological and Environmental Sciences, University of Messina, Messina, Italy.
⁸ Clinical Genetics Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
⁹ Unit of Child Neurology and Psychiatry, IRCCS "C. Mondino" Foundation, Pavia, Italy.
¹⁰ Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
¹¹ Developmental Neurology Division, IRCCS Fondazione Istituto Neurologico C. Besta, Milan, Italy.
¹² Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
¹³ Universitäts, Kinderspital Zürich, Eleonorenstiftung, Zürich, Switzerland.
¹⁴ Institut für Humangenetik Essen, Universität Duisburg-Essen, Essen, Germany.
¹⁵ Unit of Child Neuropsychiatry Giannina Gaslini Institute, Genoa, Italy.
¹⁶ Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
¹⁷ Practice of Human Genetics, Homburg (Saar), Germany.
¹⁸ Neuroradiology Unit, Giannina Gaslini Institute, Genoa, Italy.
¹⁹ Institute of Human Genetics, University of Münster, Münster, Germany.
²⁰ Private Practice for Human Genetics, Augsburg, Germany.
²¹ Department of Human Genetics, University of Regensburg, Regensburg, Germany.
²² Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
²³ Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy. enzamaria.valente@unipv.it.
²⁴ Department of Molecular Medicine, University of Pavia, Pavia, Italy. enzamaria.valente@unipv.it.
²⁵ Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Via D. L. Monza 20, 23842, Bosisio Parini, Lecco, Italy. renato.borgatti@bp.lnf.it.

PMID: 28677066
DOI: 10.1007/s00330-017-4945-2

Erratum in

Erratum to: Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation.
Romaniello R, Arrigoni F, Panzeri E, Poretti A, Micalizzi A, Citterio A, Bedeschi MF, Berardinelli A, Cusmai R, D'Arrigo S, Ferraris A, Hackenberg A, Kuechler A, Mancardi M, Nuovo S, Oehl-Jaschkowitz B, Rossi A, Signorini S, Tüttelmann F, Wahl D, Hehr U, Boltshauser E, Bassi MT, Valente EM, Borgatti R. Romaniello R, et al. Eur Radiol. 2017 Dec;27(12):5093. doi: 10.1007/s00330-017-4986-6. Eur Radiol. 2017. PMID: 28900662 No abstract available.

Abstract

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.

Keywords: Cerebellum; Dysplasia; Mutation; Neuroimaging; Tubulin genes.

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Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation

Affiliations

Tubulin-related cerebellar dysplasia: definition of a distinct pattern of cerebellar malformation

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