De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay

Disorders of brain formation can occur from pathogenicvariants in various alpha and beta tubulingenes. Heterozygous pathogenicvariants in the beta tubulin isotypeA gene, TUBB2A, have been recently implicated in brain malformations, seizures, and developmental delay. Limited information is known regarding the phenotypic spectrum associated with pathogenicvariants in this gene given the rarity of the condition. We report the sixth individual with a de novo heterozygous TUBB2A pathogenicvariant, who presented with a severe neurological phenotype along with unique features of arthrogryposis multiplex congenita, optic nerve hypoplasia, dysmorphic facial features, and vocal cord paralysis, thereby expanding the gene-related phenotype.