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The prevalence of PNKD is estimated to be 1/1,000,000 worldwide. A male preponderance is observed (1.4:1).

The age of onset is variable ranging from 1 to 77 years. PNKD is characterized by attacks of spontaneous or induced (by alcohol, caffeine, stress, menstruation, sleep deprivation or exercise) dystonia, chorea, athetosis and ballism in the limbs, face, and trunk lasting from minutes to hours without a change in the level of alertness. The movements can be partial and unilateral, but are mostly bilateral and generalized. The frequency of the attacks varies from 1-3 per day to months of attack-free intervals. Dysarthria and oculogyric crisis can also be observed during episodes of severe attacks. An aura-like sensation (paresthesia, tension in the limbs or dizziness) prior to the onset of the motor manifestations and migraine headaches may be observed. Symptomatic PNKD is most commonly reported in association with multiple sclerosis (see this term) or vascular thalamic lesions.

The pathophysiology of PNKD still remains to be elucidated but approximately 60% of patients exhibit mutations in the PNKD gene (2q35), encoding the PNKD protein (formerly named myofibrillogenesis regulator 1 protein, MR-1). Furthermore, subsequent linkage analysis in a Canadian kindred identified a novel gene locus at chromosome 2q31 (named PNKD2).

The diagnosis is purely clinical and molecular screening of the PNKD gene can help to confirm the diagnosis.

Differential diagnosis of PNKD includes: Wilson disease, paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions and choreoathetosis (ICCA syndrome), paroxysmal exertion-induced dyskinesia (PED), autosomal dominant nocturnal frontal lobe epilepsy, paroxysmal dystonic choreathetosis with episodic ataxia and spasticity, and Huntington disease (see these terms).

Prenatal diagnosis for pregnancies at increased risk of having PNKD mutations associated with familial PNKD is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at 15-18 weeks' gestation) or chorionic villus sampling (usually performed at 10-12 weeks' gestation). The disease-causing mutation of an affected family member must be identified in the family before prenatal testing can be performed.

Although sporadic cases have been reported, PNKD is usually inherited as an autosomal dominant trait with high penetrance. Haplotype analysis in the PNKD2 family demonstrated a disease penetrance of 89%.

PNKD patients do not respond to antiepileptic drugs such as carbamazepine, but clonazepam or other benzodiazepines can be helpful in some PNKD mutation carrier patients. Because PNKD may be triggered by emotional stress, fatigue, alcohol or caffeine, the avoidance of these possible precipitating factors is recommended. Deep brain stimulation may act as a potential therapeutic option in medically refractory PNKD.

No long-term sequelae are associated with PNKD. Moreover, 61% of patients with PNKD show a tendency to decrease the frequency of their attacks with age. However, in some patients, episodes may remain unchanged or worsen with age. Disappearance of attacks during pregnancy has also been described.