Broadening the phenotypic spectrum of TUBA1A tubulinopathy to syndromic arthrogryposis multiplex congenita

Am J Med Genet A. 2022 Aug;188(8):2331-2338. doi: 10.1002/ajmg.a.62866. Epub 2022 Jun 10.


The recent finding that some patients with fetal akinesia deformation sequence (FADS) carry variants in the TUBB2B gene has prompted us to add to the existing literature a first description of two fetal FADS cases carrying TUBA1A variants. Hitherto, only isolated cortical malformations have been described with TUBA1A mutation, including microlissencephaly, lissencephaly, central pachygyria and polymicrogyria-like cortical dysplasia, generalized polymicrogyria cortical dysplasia, and/or the "simplified" gyral pattern. The neuropathology of our fetal cases shows several common features of tubulinopathies, in particular, the dysmorphism of the basal ganglia, as the most pathognomonic sign. The cortical ribbon anomalies were extremely severe and concordant with the complex cortical malformation. In conclusion, we broaden the phenotypic spectrum of TUBA1A variants, to include FADS.

Keywords: TUBA1A; arthrogryposis; brain malformation; microlissencephaly; prenatal diagnosis; tubulinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthrogryposis* / diagnosis
  • Arthrogryposis* / genetics
  • Humans
  • Lissencephaly* / genetics
  • Malformations of Cortical Development* / genetics
  • Mutation
  • Polymicrogyria*
  • Tubulin / genetics


  • TUBA1A protein, human
  • Tubulin