To better delineate the clinical picture of TUBB4A mutations and present three new likely pathogenic variants.

DYT-TUBB4A, formerly known as DYT4, has only been described in one large family and two individual cases. The clinical picture highlighted in the original family comprises laryngeal and cervical dystonia extending to generalized dystonia, plus a “hobby horse” gait disorder. The variant identified as causative in the original family was a heterozygous missense mutation R2G in exon 1 of the TUBB4Agene.

We screened three families including a total of nine definitely affected members with a clinical picture resembling the original description. 

Three novel variants in the TUBB4A gene have been identified: D295N, R46M, Q424H. In silicomodeling showed that all variants have similar characteristics to R2G. The variants segregate with the disease in 2 of the families. All three variants would be classified as likely pathogenic. The clinical picture particularly included laryngeal dystonia (often the site of onset), associated with cervical and upper limb dystonia and frequent generalization. Laryngeal dystonia was extremely prevalent (>90%) both in the original cases and in this case series. The “hobby horse” gait was not demonstrated in this case series. 

Laryngeal dystonia in TUBB4A mutations must be highlighted. Nevertheless, TUBB4A mutations remain an exceedingly rare cause of laryngeal or other isolated dystonia.