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


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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:December 2017
Deposited On:07 Feb 2018 09:34
Last Modified:19 Feb 2018 10:53
Publisher:Springer
ISSN:0938-7994
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s00330-017-4945-2
PubMed ID:28677066

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