early-onset primary dystonia (dyt1)

dystonia is a movement disorder that causes sustained muscle contractions, repetitive twisting movements, and abnormal postures of the trunk, neck, face, or arms and legs. inherited dystonias can be classified as primary dystonia, dystonia-plus, heredo-degenerative dystonia, and paroxysmal dyskinesias with dystonia. the primary dystonias are those with no other neurologic abnormalities. primary dystonias were originally described as idiopathic since no neurophysiologic, neurochemical, or pathologic findings provided clues to the underlying etiology however, many are now known to have a genetic basis. early-onset primary dystonia (dyt1) typically presents in childhood or adolescence and only on occasion in adulthood. dystonic muscle contractions causing posturing of a foot, leg, or arm are the most common presenting findings. dystonia is usually first apparent with specific actions e.g., writing or walking. over time, the contractions frequently (but not invariably) become evident with less specific actions and spread to other body regions. no other neurologic abnormalities are present, except for postural arm tremor. disease severity varies considerably even within the same family. isolated writers cramp may be the only sign. dyt1 is diagnosed by molecular genetic testing of the tor1a gene revealing the three-base pair deletion c.904_906delgag in most affected individuals (%99). dyt1 is inherited in an autosomal dominant manner with reduced penetrance. offspring of an affected individual or an asymptomatic individual known to have a tor1a disease-causing mutation have a 50% chance of inheriting the disease-causing mutation and a 30% to 40% chance of developing clinical findings. we suggest that testing be recommended in individuals with age of onset of dystonia below 30 years and/or a positive family history of early onset primary torsion dystonia. there are four main reasons an individual may want to be tested for the dyt1 gag mutation: 1. a positive test result will help provide an answer for a symptomatic individual. this can help establish a prognosis and lead to appropriate patient management. due to the reduced penetrance, not all individuals who have the dyt1 mutation develop the symptoms of dystonia. in the absence of a positive family history for the dyt1 mutation, a negative test result does not necessarily rule out another inherited form of dystonia. 2. other family members of the affected individual can obtain information as to whether or not they have the dyt1 mutation. this knowledge can help them, and their physicians, determine their risk for developing the symptoms associated with dystonia. 3. a positive test for the dyt1 mutation can allow for genetic counseling and family planning. genetic counseling is important in helping individuals and family members understand what is involved in a genetic test, how to interpret the results, and what a positive result means. 4. some medications may be contraindicated in patients with dystonia. dopamine receptor blocking agents (drbas) are a class of drugs that can cause and/or aggravate existing dystonia. therefore, knowing that an individual may have dystonia will help them avoid the detrimental effects of drbas. this class of drugs includes many antipsychotic medications and medications for the treatment of nausea and vomiting. from mid 2008 we have checked 6 patients (referred or diagnosed by dr. aryani) in our lab.four of the patients were positive for dyt1 (one patient was from turkey). for the three of them treatment with dbs have been started soon. it was interesting that one of the patients had been presented with limbs resting and postural tremor (motor restlessness) and the head & neck were spared.