Dystonia-Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia. (P2.139)

Objective: Evaluate genetic screening in spasmodic dysphonia Background: Spasmodic dysphonia is a disabling, focal dystonia of the larynx with heterogeneous manifestations and associated with familial risk factors. There is scarce data to allow a deeper understanding of etiology and pathophysiology; current treatments are largely targeted at symptom control with chemodenervation and voice therapy. Screening for dystonia-causing genetic mutations has the potential to allow accurate diagnosis, inform about genotype-phenotype correlations and allow a better understanding of mechanisms of disease. Methods: We describe a cohort of patients presenting with spasmodic dysphonia including demographic data, clinical features, family history and treatments administered. The following dystonia genes previously associated with spasmodic dysphonia were screened: TOR1A (DYT1), TUBB4 (DYT4), and THAP1 (DYT6). Results:A cohort of 77 patients was studied comprising 88[percnt] females and 22[percnt] males. Most were white (69/77, 89[percnt]). A definite family history of neurological disorder was present in 18[percnt] (14/77), a probable family history was present in 19[percnt] (15/77). Average age of symptom onset was 42y (SD±14.6). Six patients (7[percnt]) had associated tremor. All were treated with BTX, and 9/77 (11[percnt]) received oral medications. Genetic screening was negative in all patients for GAG deletions in TOR1A (DYT 1) and in the 5 exons currently associated with disease-causing mutations in TUBB4 (DYT4). Only one patient tested positive for a mutation in THAP1 (DYT 6). Conclusions: Genetic screening of the current dystonia genes with known laryngeal involvement, TOR1A, THAP1 and TUBB4, appears to have a low diagnostic yield in sporadic spasmodic dysphonia. In our cohort only one patient tested positive for THAP1, notably, this patient had a positive family history of dystonia. Clinicians should make use of genetic testing in cost-effective ways and consider ordering selected testing in cases where a strong clinical suspicion is based on family history or particular phenotypes. Disclosure: Dr. De Gusmao has nothing to disclose. Dr. Sharma has nothing to disclose. Dr. Moses has nothing to disclose. Dr. Multhaupt-Buell has nothing to disclose. Dr. Song has nothing to disclose. Dr. Fuchs has nothing to disclose. Dr. Franco has nothing to disclose. Dr. Ozelius has nothing to disclose.,