Voice and Swallowing Dysfunction in X-linked Dystonia Parkinsonism Phillip C. Song, MD ; Hoai Le, BS; Patrick Acuna, MD; Jan Kristopher Palentinos De Guzman, MD; Nutan Sharma, MD, PhD; Taylor N. Francouer, BA; Marisela E. Dy, MD; Criscely L. Go, MD Objectives: To systematically characterize and describe voice and swallowing manifestations in patients with X-linked dystonia parkinsonism (XDP) and correlate with quality-of-life (QOL) measures. Methods: Thirty-four patients with XDP with communication and swallowing difficulties underwent neurological exami- nation, head and neck examination, nasopharyngoscopy, QOL surveys (Swallowing Quality of Life questionnaire [SWAL-QOL] and Voice Handicap Index [VHI]), and functional endoscopic evaluation of swallowing (FEES) to assess the extent of dysfunction. Results: All patients showed high rates of lingual, oromandibular, and laryngeal dysfunction, as well as severe QOL changes in swallowing and communication ability. The most common head and neck manifestations of dystonic symptoms were difficulty coordinating the mouth and tongue (79%), uncontrollable tongue thrusting (53%), and jaw opening (35%). Laryngeal symptoms including vocal strain (adductor voice breaks) or stridor (32%), as well as velopharyngeal insufficiency (20%), were also identified. Of the patients with laryngeal symptoms, 18% had respiratory dystonia. Swallowing assessments showed significant abnormalities in oral bolus control and oropharyngeal dysphagia. FEES examinations showed that 87.5% of the study group had penetration or aspiration. QOL scores showed an average VHI of 94.4 (severe dysfunction), and SWAL-QOL showed an average of 37.7 (severe dysfunction). Conclusion: Swallowing and voice impairment in XDP is not well characterized and presents a more distinctive phenome- nology than other neurological disorders, with a unique set of challenges for treatment. This is the first study to systematically evaluate laryngeal and pharyngeal dysfunction in XDP patients and correlate with QOL measures. Key Words: Dysphagia, X-linked dystonia parkinsonism, functional endoscopic evaluation of swallowing, dysphonia, quality of life. Level of Evidence: 4 Laryngoscope, 9999:1–7, 2019 INTRODUCTION X-linked dystonia parkinsonism (XDP/DYT3) (Online Mendelian Inheritance in Man [OMIM] #314250) is an adult-onset neurodegenerative disorder characterized by dystonia and parkinsonism. 1–3 The phenomenology of XDP was first described by Lee et al in 1976 1(p362) as “dys- tonia musculorum deformans” and has been referred to in the past as Lubag’s disease in reference to the local Filipino dialect meaning “intermittent twisting of posture.” It occurs primarily in Filipino males whose mothers descend from the island of Panay, but in rare cases it can occur in females. 1,4 It is estimated that the preva- lence of XDP is five per 100 thousand on the island of Panay. Age of onset occurs in the third to fourth decade, and clinical symptoms begin with a focal dystonia that spreads to multiple body regions that combines with, or may be replaced by, parkinsonism. 2,3 Studies revealed that dystonias involving the head and neck are common and are the initial site of onset in over half the cases, with 27% presenting with blepharospasm, oromandibular, or lingual dystonias; and 25% presenting with cervical dys- tonia. 3 Ninety-seven percent of patients progressed to gen- eralized dystonia with features of parkinsonism within 15 years after initial symptom manifestations. 1–3,5,6 Clinically, XDP is a severely disabling disorder, with painful, uncontrollable muscle spasm that can lead to dysarthria, dysphagia, loss of ambulation, and profound functional disability. 2,7 Death typically occurs in the fifth decade, with the main cause of death being malnutrition and aspiration pneumonia. 8–10 Oromandibular and lingual dystonia affect communication and swallowing. 8 Adductor laryngeal dystonia has been reported in this group and can affect breathing requiring a tracheostomy. 9 Genetic testing for XDP is based on analyzing mutations in the TAF1/DYT3 gene, 10–12 which encodes TATA-binding pro- tein (TBP)-associated factor-1 (TAF1), involved in tran- scriptional regulation. 8,13–20 From the Department of Otolaryngology, Massachusetts Eye and Ear Infirmary (P.C.S., H.L.); The Collaborative Center for X-linked Dystonia Parkinsonism, Department of Neurology, Massachusetts General Hospital (P.A., J.K.P.DG., N.S.); the Department of Neurology, Massachusetts General Hospital (T.N.F.); the Department of Neurology, Boston Children’s Hospital/Massachusetts General Hospital (M.E.D.), Boston, Massachusetts, U.S.A.; the Sunshine Care Foundation (P.A.), Roxas City, Philippines; and the Department of Neurology, Jose R. Reyes Memorial Medical Center (C.L.G.), Manila, Philippines. Editor’s Note: This Manuscript was accepted for publication on February 12, 2019. Institutions where work was performed: Massachusetts General Hospital; the Massachusetts Eye and Ear Infirmary; the Jose R. Reyes Memorial Medical Center; and The Collaborative Center for X-linked Dys- tonia Parkinsonism. This study was supported by The Collaborative Center for X-linked Dystonia Parkinsonism, Department of Neurology, Massachusetts Gen- eral Hospital, Boston, Massachusetts. The authors have no funding, finan- cial relationships, or conflicts of interest to disclose. Send correspondence to Phillip C. Song, MD, Massachusetts Eye and Ear Infirmary, 243 Charles Street Boston, MA 02114. E-mail: phillip_song@meei.harvard.edu DOI: 10.1002/lary.27897 Laryngoscope 00: 2019 Song et al.: Voice and Swallowing Dysfunction in XDP 1 The Laryngoscope © 2019 The American Laryngological, Rhinological and Otological Society, Inc.