Clinical and MRI characteristics of tubulinopathies. A clinical case of TUBA1A associated pahygiria and cerebellar hypoplasia


  • Daniela Deneva UHATNP "St.Naum"
  • I. Aleksandrova UHATNP "St.Naum"; Medical university – Sofia
  • V. Bojinova UHATNP "St.Naum"


pachygyria, polymicrogyria, TUBA1A-tubulinopathy


Tubulin is a protein that polymerizes into long chains or filaments and form microtubules that play key roles in cell division, neuronal migration, protein transport, and ciliary motility.
Tubulinopathies are brain malformations caused by mutations in one of seven genes encoding different isotypes of tubulin: alpha- (TUBA1A), beta- (TUBB2A, TUBB2B, TUBB3, TUBB4A, TUBB) and gamma-tubulin (TUBG1). TUBA1A is the first tubulin isotype associated with cortical malformations and is the most frequently mutated tubulin gene. TUBA1A mutations represent a novel form of lissencephaly that ranges from predominant perisylvian to diffuse pachygyria and is associated with fusion of nucleus caudatus and putamen due to absence of the anterior limb of internal capsule, with rounded thalamus, cerebellar hypoplasia and corpus callosum dysplasia.
This specific MRI pattern is associated with severe congenital microcephaly, mental retardation, spastic quadriparesis and epilepsy.
The described combination between the clinical picture and MRI pattern should direct the clinician toward genetic testing for TUBA1A mutations.
Clinical case: We describe the case of a girl aged 4 years, born after a normal pregnancy and delivery, but with a delayed motor and speech development, microcephaly, pyramidal reflex changes, more pronounced on the left, atactic gait and epileptic spasms with onset at the age of 2 years. MRI at 7 months showed hypoplastic corpus callosum, delayed myelination, pachygyria affecting the frontal lobes bilaterally, more pronounced on the right, fusion of putamen and nucleus caudatus on the right and prominent retrocerebellar cyst. Genetic analysis, performed at 1 year of age, revealed a pathogenic variant (mosaic) in the TUBA1A gene (c.1265 G>A, variant p.Arg422His).
CONCLUSION: The presented case is an example of an early diagnosis based on the characteristic MRI image at 7 months of age, confirmed later by genetic testing. Pachygyria of both frontal lobes determines the cognitive deficit, pyramidal reflex changes and the epileptic syndrome.


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How to Cite

Deneva, D., Aleksandrova, I., & Bojinova, V. (2023). Clinical and MRI characteristics of tubulinopathies. A clinical case of TUBA1A associated pahygiria and cerebellar hypoplasia. Bulgarian Neurology, 24(3), 122–124. Retrieved from