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

Eur Radiol. 2017 Dec;27(12):5080-5092. doi: 10.1007/s00330-017-4945-2. Epub 2017 Jul 4.

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.

MeSH terms

  • Adult
  • Brain Stem / diagnostic imaging
  • Cerebellum / abnormalities*
  • Cerebellum / diagnostic imaging
  • Cerebellum / pathology
  • Child
  • Child, Preschool
  • Developmental Disabilities / diagnostic imaging
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Female
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation*
  • Nervous System Malformations / diagnostic imaging*
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Neuroimaging / methods*
  • Tubulin / genetics*
  • Young Adult

Substances

  • TUBB2B protein, human
  • TUBB3 protein, human
  • Tubulin

Supplementary concepts

  • Cerebellar Hypoplasia