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.

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, M. F.; Berardinelli, A.; Cusmai, R.; D'Arrigo, S.; Ferraris, A.; Hackenberg, A.; Kuechler, A.; Mancardi, M.; Nuovo, S.; Oehl-Jaschkowitz, B.; Rossi, A.; Signorini, S.; Tuttelmann, F.; Wahl, D.; Hehr, U.; Boltshauser, E.; Bassi, M. T.; Valente, E. M.; Borgatti, R.. - In: EUROPEAN RADIOLOGY. - ISSN 0938-7994. - 27:12(2017), pp. 5080-5092. [10.1007/s00330-017-4945-2]

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

Nuovo S.;
2017

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.
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; Nervous System Malformations; Neuroimaging; Tubulin; Young Adult; Mutation
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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, M. F.; Berardinelli, A.; Cusmai, R.; D'Arrigo, S.; Ferraris, A.; Hackenberg, A.; Kuechler, A.; Mancardi, M.; Nuovo, S.; Oehl-Jaschkowitz, B.; Rossi, A.; Signorini, S.; Tuttelmann, F.; Wahl, D.; Hehr, U.; Boltshauser, E.; Bassi, M. T.; Valente, E. M.; Borgatti, R.. - In: EUROPEAN RADIOLOGY. - ISSN 0938-7994. - 27:12(2017), pp. 5080-5092. [10.1007/s00330-017-4945-2]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1540321
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