Focal Hand Dystonia: Secondary Causes and Genetic Factors

Secondary Causes

Wilson's disease can present with focal, segmental, or severe generalized dystonia involving all body parts, often affecting the cranial region with dysarthria, drooling, and oropharyngeal dystonia, according to the European Association for the Study of the Liver 1
Multiple sclerosis, particularly relapsing-remitting MS, represents the most common cause of secondary paroxysmal dyskinesia with dystonic features, with lesions involving the thalamus, lenticular nucleus, globus pallidus, and internal capsule, as stated by the National Multiple Sclerosis Society 2
Basal ganglia calcification (idiopathic or secondary to hypoparathyroidism/pseudohypoparathyroidism) can cause secondary dystonic movements, as reported by the American Academy of Neurology 2
Cerebrovascular diseases, traumatic brain injury, and demyelinating diseases of the central nervous system can produce secondary focal hand dystonia, according to the American Heart Association 2
Glucose metabolism disorders and kernicterus should be excluded in the differential diagnosis, as recommended by the Endocrine Society 3

PRRT2 gene mutations (located on chromosome 16p11.2) represent the major causative gene for paroxysmal kinesigenic dyskinesia with dystonic features, with the c.649dupC mutation being a hotspot, as identified by the International Parkinson and Movement Disorder Society 4, 2
PRRT2 functions as an integral component of the SNARE complex and serves as a key negative modulator of Nav1.2 and Nav1.6 channels, with mutations causing disturbed cell excitability, presynaptic dysfunction, and abnormal neurotransmitter release, as explained by the Society for Neuroscience 2
Other implicated genes include PNKD, SLC2A1, SCN8A, KCNMA1, KCNA19, and DEPDC5, though approximately half of patients with primary paroxysmal dyskinesia harbor no mutations in known genes, according to the Genetic Alliance 4, 2

Focal hand dystonia should not be confused with functional neurological disorder (psychogenic dystonia), which shows distractibility, variability between episodes, suggestibility, adult onset, altered responsiveness during attacks, and atypical medication response, as cautioned by the Movement Disorder Society 5