Movement Disorders

Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. Using whole-exome sequencing followed by Sanger sequencing, we identified three truncating mutations within PRRT2 (NM_145239.2) in eight Han Chinese families with histories of paroxysmal kinesigenic dyskinesia: c.514_517delTCTG (p.Ser172Argfs*3) in one family, c.649dupC (p.Arg217Profs*8) in six families and c.972delA (p.Val325Serfs*12) in one family. These truncating mutations co-segregated exactly with the disease in these families and were not observed in 1,000 control subjects of matched ancestry. PRRT2 is a newly discovered gene consisting of four exons encoding the proline-rich transmembrane protein 2, which encompasses 340 amino acids and contains two predicted transmembrane domains. PRRT2 is highly expressed in the developing nervous system, and a truncating mutation alters the subcellular localization of the PRRT2 protein. The function of PRRT2 and its role in paroxysmal kinesigenic dyskinesia should be further investigated.

Wilson disease is an inherited autosomal recessive disorder of copper balance leading to hepatic damage and neurological disturbance of variable degree. The defective gene, ATP7B, encodes a hepatic copper-transporting protein, which plays a key role in human copper metabolism. Our knowledge of the genetic basis of Wilson disease has increased dramatically; however, understanding of genotype-phenotype correlation and multifarious effects of copper toxicity as basis for targeted and individualised therapy strategies is still insufficient. Clinical manifestations are related to copper accumulation predominantly in the liver and brain and include hepatic disease ranging from mild hepatitis to acute liver failure or cirrhosis and/or neurological symptoms such as dystonia, tremor, dysarthria, psychiatric disturbances. Mixed presentations occur frequently. Early recognition by means of clinical, biochemical or genetic examination and initiation of therapy with copper chelators, zinc salts or even liver transplantation in cases of acute and chronic liver failure are essential for favourable outcome. Copyright © 2010 Elsevier Ltd. All rights reserved.

We studied 46 patients with paroxysmal dyskinesia and classified them according to phenomenology, duration of attacks, and etiology. There were 13 patients, 7 females, who had paroxysmal kinesigenic dyskinesia (PKD), 10 with attacks lasting 5 minutes or less (short lasting) and 3 with attacks lasting longer than 5 minutes (long lasting). Twenty-six patients, 18 females, had paroxysmal nonkinesigenic dyskinesia (PNKD), 9 with short-lasting and 17 with long-lasting PNKD. Five patients, 3 females, had paroxysmal exertion-induced dyskinesia (PED), 3 with short-lasting PED and the other 2 with long-lasting PED. In addition, there was 1 patient with paroxysmal hypnogenic dyskinesia (PHD) and 1 with paroxysmal superior oblique myokymia. Only 2 patients, 1 with PKD and 1 with PHD, had family history of paroxysmal dyskinesias. No specific cause could be identified in 21 patients; in the other 23 patients the etiologies included the following: psychogenic (9 patients), cerebrovascular diseases (4), multiple sclerosis (2), encephalitis (2), cerebral trauma (2), peripheral trauma (2), migraine (1), and kernicterus (1). Nine of 10 (90%) patients with PKD improved with medications, mostly anticonvulsants, compared with only 7 of 19 (37%) with PNKD. This new classification, based chiefly on precipitating events, allowed appropriate categorization of the attacks in all our patients with paroxysmal dyskinesias.