Blepharospasm plus Cervical Dystonia with Predominant Anterocollis: A Distinctive Subphenotype of Segmental Craniocervical Dystonia

BACKGROUND: Dystonia of the eyelids often spreads to affect other muscles in the craniocervical region. Certain blepharospasm-plus subphenotypes may be clinically unique. METHODS: Seven subjects with the subphenotype of late-onset blepharospasm with apraxia of eyelid opening and cervical dystonia with predominant anterocollis were identified from a database of over 1800 patients with primary dystonia. RESULTS: Blepharospasm was the first affected site in 6/7 subjects, followed by spread of the disease to the cervical muscles. Although four patients also had other forms of dystonia (laryngeal, lower face), none showed spread outside the craniocervical region. A family history of dystonia was present in 4/7. No mutations were identified in THAP1 or TOR1A. Overall, blepharospasm was difficult to treat, typically requiring both myectomy and substantial doses of botulinum toxin into the pretarsal orbicularis oculi muscles. In one subject, anterocollis markedly improved after deep brain stimulation. DISCUSSION: Delineation and characterization of craniocervical dystonia subphenotypes may serve to guide genetic and therapeutic studies, in addition to clinical interventions. The blepharospasm with apraxia of eyelid opening and anterocollis subphenotype can be therapeutically challenging.