Dystonia 23

Clinical Features

Uitti and Maraganore (1993) reported a large family of German origin in which 5 individuals, including a pair of monozygotic twin brothers, had adult-onset cervical dystonia, typically during the fourth and fifth decades of life. Physical examination showed variable limitation of the neck, torticollis, and hypertrophy of the sternocleidomastoid muscles. Four patients had head tremor, and 3 had limb tremor. Five additional family members were diagnosed with possible cervical dystonia.

Groen et al. (2011) reported a 3-generation Dutch family in which 5 individuals had a movement disorder characterized by dystonia and myoclonus. The age at symptom onset ranged widely from 4 to 62 years. Symptoms included writer's cramp, dysphonia, torticollis, and foot dystonia. Two patients had generalized myoclonus, whereas the other 3 had myoclonus localized to the voice, face, trunk, or limbs. Three patients had action-induced myoclonus of the lower limbs, and 3 patients reported that the myoclonus responded to alcohol. Patients also showed high-frequency continuous myoclonus in the legs while standing, resulting in unsteadiness. Other more variable features included panic attacks and hyperventilation syndrome. Brain imaging was normal in 2 patients; 1 patient had mild cerebral and cerebellar atrophy. Electrophysiologic studies performed in 3 patients showed semirhythmic or irregular bursts, suggestive of a subcortical origin with possible cerebellar involvement. Groen et al. (2015) noted that 3 patients reported by Groen et al. (2015) had cardiac arrhythmias and attacks of painful limb cramps.

Inheritance

The transmission patterns in the family with cervical dystonia reported by Uitti and Maraganore (1993) and in the family with myoclonus-dystonia reported by Groen et al. (2011) were both consistent with autosomal dominant inheritance.

Mapping

In the family with cervical dystonia reported by Uitti and Maraganore (1993), Jarman et al. (1999) excluded linkage to the DYT7 locus (602124) on chromosome 18p, suggesting further genetic heterogeneity of the phenotype.

By linkage analysis in the family reported by Uitti and Maraganore (1993), Xiao et al. (2012) found strongest linkage to markers D9S159 and D9S1818 at 9q34 (maximum lod, 2.71).

Molecular Genetics

Associations Pending Confirmation

For discussion of a possible association between dystonia and mutation in the CACNA1B gene, see 601012.0001.

For discussion of a possible association between dystonia and mutation in the CIZ1 gene, see 611420.0001.