Purpose or Case Report: Tubulins are a component of microtubules, which are critical to the processes of mitosis, axon navigation, and neuron migration, all key factors in brain development. Mutations in tubulin genes can alter the normal function and structure of microtubules, leading to complex disorders of brain development and brain malformations. Disorders of microtubules formation affect multiple aspects of brain development, resulting in multiple malformations that can be recognized on cranial MRI. A significant characteristic is the wide spectrum of severity, from severe forms often present at birth to milder conditions, sometimes seen in asymptomatic parents of affected individuals.
The purpose of this educational poster is to present the main postnatal and prenatal MRI patterns that can help to suspect a tubulinopathy and guide subsequent genetic testing for confirmation.
Methods & Materials: Authors present a retrospective review of a series of postnatal and prenatal cases, with clinical and genetic correlation. The main MRI findings that allow recognize these genetic disorders include dysgyria, dysmorphism and unusual orientation of the basal ganglia, corpus callosum hypoplasia, brain stem and cerebellar hypoplasia, and in certain types (beta tubulinopathies) congenital fibrosis of the extraocular muscles, facial weakness and dysmorphisms, as well as progressive peripheral neuropathy.
Results: Three prenatal main patterns are reported to date as early as 21-24 weeks og gestation: microlissencephaly, lissencephaly, and dysgyria, combined with cerebellar hypoplasia, pons hypoplasia and corpus callosum dysgenesis. Particularly important is recognizing the named “Mild Tubulinopathy”, with major and minor criteria that can help identify this entity in utero. Distortion of anterior midline, asymmetric ventriculomegaly, gray matter subependymal heterotopias, low cerebellar and brain stem biometrics, anomalous gyral pattern (disgyria), and suspected asymmetry basal ganglia are key findings in fetal MRI. Around 50% of these tubulinopathies are inherited from one of the parents, so TRIO MRI and Exome investigations are strongly recommended (fetus and both parents).
Conclusions: MRI is essential to detect and adequately characterize CNS abnormalities in fetuses and children, also in tubulinopathies. It is recommendable to integrate the MRI information with clinical and genetic data, working in a multidisciplinary way, for more appropriate counseling.