Tubulinopathies refer to a wide spectrum of cortical malformations that result from defects in genes encoding the tubulin protein that regulates neuronal migration during brain development.
Some series report a high prevalence of seizures during infancy which may the initial reason for brain imaging in patients with tubulin disorders. They may also be encountered in children with developmental delay.
Tubulins play an important role in neuronal migration in the developing foetal brain. The roles of alpha and beta tubulins in brain development has been recognized for some years while the role of other tubulins, such as g-tubulin, have only been more recently been described 1.
While the majority of tubulinopathies result from de novo mutations, others such as TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB5 and TUBG1 are autosomal dominant in inheritance 2.
As with most brain malformations, MRI remains the modality of choice, and these disorders may be seen during foetal MR before birth. Five common cortical malformation patterns have been described in tubulinopathies:
- central pachygyria
- polymicrogyria-like cortical dysplasia
- simplified gyral pattern
Basal ganglia dysmorphism or abnormal orientation is a pathognomonic association that occurs in 75% of cases 2. The usual appearance is dysgenesis or agenesis of the anterior limb of the internal capsule (absent ALIC sign) 4, resulting in a round, fused appearance of the caudate and putamen. The head of the caudate protrudes further into the lateral ventricle, giving the frontal horn a hooked configuration 2. There is also a high association with ventriculomegaly, corpus callosal agenesis (up to 40%), and cerebellar hypoplasia of varying degrees in these patients as well 3.
- 1. Parrini E, Conti V, Dobyns WB, Guerrini R. Genetic Basis of Brain Malformations. (2016) Molecular syndromology. 7 (4): 220-233. doi:10.1159/000448639 - Pubmed
- 2. Bahi-Buisson N, Poirier K, Fourniol F, Saillour Y, Valence S, Lebrun N, Hully M, Bianco CF, Boddaert N, Elie C, Lascelles K, Souville I, , Beldjord C, Chelly J. The wide spectrum of tubulinopathies: what are the key features for the diagnosis?. (2014) Brain : a journal of neurology. 137 (Pt 6): 1676-700. doi:10.1093/brain/awu082 - Pubmed
- 3. Mutch CA, Poduri A, Sahin M, Barry B, Walsh CA, Barkovich AJ. Disorders of Microtubule Function in Neurons: Imaging Correlates. (2016) American Journal of Neuroradiology. 37 (3): 528. doi:10.3174/ajnr.A4552 - Pubmed
- 4. Tubulinopathies. (2018) Topics in magnetic resonance imaging : TMRI. 27 (6): 395-408. doi:10.1097/RMR.0000000000000188 - Pubmed