The brains of identical twins with juvenile-onset dystonia were examined at Emory University, Atlanta, Georgia. Clinically, the twins had only a mild developmental delay until age 12 years, and they then showed a rapidly progressive generalized dystonia and dementia, with death occurring at ages 21 and 22 years. Clinical findings and course were distinct from primary and secondary dystonias previously described. The twins were born with cleft lip and palate, their limbs were small, and skeletal abnormalities included high foreheads, hypoplastic scapulas, and kyphoscoliosis by age 10 years. Achalasia was diagnosed at age 2, cataracts at age 3, and sensory-neural deafness at age 4. Dystonia developed first in the leg by age 14, and progressed over 5 years from a clumsy gait to an inability to walk. Oculogyric and opisthotonic crises occurred as the dystonia became generalized. Grimacing, dysarthria, tongue protrusion, and dysphagia with pseudobulbar palsy occurred by age 14.

Macroscopically, the brains were unremarkable. Microscopic examination showed diffuse glial fibrillary acidic protein-immunoreactive astrocytes, and iron accumulation in neurons of the globus pallidus and substantia nigra. Additional degenerative findings included; 1) eosinophilic, rod-like cytoplasmic inclusions found in neocortical and thalamic neurons that were actin depolymerizing factor/cofilin-immunoreactive and rarely actin positive; and 2) eosinophilic spherical structures in the striatum that were actin- and actin depolymerizing factor/cofilin-positive. Aggregation of actin is a novel finding in neurodegenerative disease associated with dopa-unresponsive dystonia. [1]

COMMENT. An extensive aggregation of actin and actin regulatory proteins ADF/cofilin in twins with progressive and fatal dystonia is indicative of a dysfunction of regulatory turnover of active filaments in the cytoskeletal system. This is a novel neuropathological finding in a neurodegenerative disease causing dystonia. Other well known examples of a secondary dystonia include Wilson’s disease, Hallervorden-Spatz disease, and Huntington’s disease. Secondary dystonias may be complicated by parkinsonism, myoclonus, and tremor, and some are without defined pathology, as in drug-induced and occupational, and with known pathology, such as traumatic, metabolic, and vascular. Another example of secondary dystonia is the myoclonus-dystonia syndrome, with onset in childhood.