A movement disorder that manifests in childhood and advances to total incapacitation within a few years.
Primary Dystonia; Idiopathic Torsion Dystonia; Dystonia Musculorum Deformans (Early Onset Primary Torsion Dystonia); Ziehen-Oppenheim Disease; Ziehen-Schwalbe-Oppenheim Syndrome.
First described in 1908 by S. Schwalbe in a Jewish family and in 1911, Oppenheim termed this condition as dystonia musculorum deformans (DMD).
About 5 to 30:100,000 live births. A female predilection has been reported for focal and segmental primary torsion dystonia. Primary torsion dystonia is more common among the Ashkenazi Jewish population and Amish-Mennonite families.
Autosomal dominant inheritance for both early-onset and late-onset primary torsion dystonia with a low penetrance. The early form has a 30 to 40% penetrance, and the late-onset primary torsion dystonia a 10 to 15% penetrance. Negative family history does not exclude the diagnosis.
Early onset torsion dystonia-1 (DYT1) is caused by heterozygous mutation in the TOR1A gene encoding the ATP-binding protein torsin-A, on chromosome 9q34. The mutation of the late-onset primary torsion dystonia has been mapped to 8p11-q22 (DYT6) and to 18p (DYT7). The pathophysiology of dystonia remains unclear. Dystonia may occur because of abnormal neurochemical transmission in the basal ganglia, brain stem, or both. It has been hypothesized that the dystonic movements originate from a functional disturbance of the basal ganglia (most likely because of an increased striatal inhibition on globus pallidum and substantia nigra) in combination with a severely altered pattern of normal spontaneous neuronal activity. This may affect the thalamic control on planning and execution of movements, as well as brain stem and spinal inhibitory reflexes, and result in the dystonic pattern of pathological cocontraction of agonist and antagonist muscles with abnormal recruitment of more extraneous muscle groups (as seen in the electromyography [EMG]).
There is no definitive diagnostic test for dystonia. The diagnosis is mainly based on clinical findings of involuntary movements. So far, neuroimaging studies (CT, MRI scans), postmortem examinations, and laboratory studies have not revealed any pathological findings in primary torsion dystonia. Perinatal asphyxia is the most common cause for secondary dystonia in children, and among other causes with similar symptoms such as encephalitis, traumatic brain injury, neurotoxins, and drugs, has to be ruled out. Its onset is usually—but not always—in the first 3 years of life. In primary torsion dystonia, most patients are and remain mentally normal; however, patients with severe developmental delay have also been described.
The hallmark of primary torsion dystonia is sustained muscle contractions that often result in twisting, repetitive movements, and/or abnormal postures. Depending on the anatomical sites that are affected by the dystonic movements, primary ...