Disorders of Microtubule Function in Neurons: Imaging Correlates

Area of Science:

• Neuroimaging
• Genetics
• Developmental Biology

Background:

• Malformations of cortical development are linked to mutations in microtubules and associated proteins.
• Phenotype-genotype correlations in these disorders remain challenging.
• Previous studies primarily focused on cerebral cortical findings.

Purpose of the Study:

• To characterize and compare the magnetic resonance imaging (MRI) findings in patients with mutations affecting microtubule function.
• To establish early phenotype-genotype correlations for rare cortical development disorders.

Main Methods:

• Retrospective analysis of MRIs from 18 patients with tubulin gene mutations (TUBA1A, TUBB2B, TUBB3) and 15 patients with microtubule-associated protein gene mutations (LIS1, DCX, DYNC1H1).
• Detailed visual assessment of cortical gyral patterns, basal ganglia, white matter, brain stem, cerebellum, and corpus callosum.
• Comparison of imaging features between the two patient groups.

Main Results:

• All patients exhibited abnormal MRI findings.
• Tubulin gene mutations were associated with microcephaly, ventriculomegaly, dysgyria, absent corpus callosum, and small pons.
• Microtubule-associated protein mutations predominantly caused pachygyria and agyria, with fewer subcortical abnormalities.

Conclusions:

• Comparing MRI findings in tubulin and microtubule-associated protein mutation cohorts aids in establishing phenotype-genotype correlations.
• This comparative imaging analysis can assist in the identification and diagnosis of these rare neurodevelopmental disorders.