Table 2.

Disorders to Consider in the Differential Diagnosis of Familial PNKD

MOI /
Category		DisorderGene(s)Age of OnsetNeurologic Presentation
AD /
Paroxysmal dyskinesias		Familial paroxysmal kinesigenic dyskinesia
(See PRRT2-Associated Paroxysmal Movement Disorders.)		PRRT2 1Typically childhood & adolescenceAttacks of dyskinesia:
  • Are triggered by sudden movement;
  • Last secs to mins;
  • May occur 100x/day;
  • Do not cause loss of consciousness, & persons have normal ictal EEG.
Clinical spectrum can incl:
  • Episodic ataxia;
  • Hemiplegic migraine.
Some persons have personal or family history of afebrile convulsions.
Glucose transporter type 1 deficiency syndrome SLC2A1 InfancyPED:
  • Lasts 5-30 mins;
  • Can be part of a complex neurologic syndrome incl epilepsy, DD, ataxia, & spasticity.
Autosomal dominant nocturnal frontal lobe epilepsy ManyInfancy to adulthood
  • Incl dystonia, chorea, & ballism
  • Episodes generally occur during non-REM sleep, often evoking arousal followed again by sleep.
  • Persons are able to recall the episodes in the morning.
KCNMA1-related paroxysmal dyskinesia (OMIM 609446) KCNMA1 Childhood
  • Attacks of PNKD can be triggered by alcohol or coffee.
  • Persons also have epilepsy &/or DD.
ADCY5-related dyskinesia ADCY5 ChildhoodChoreiform, myoclonic, &/or dystonic movements w/attacks of paroxysmal dyskinesia, exacerbated by anxiety, not precipitated by startle, caffeine, or alcohol
Alternating hemiplegia of childhood (See ATP1A3-Related Neurologic Disorders.) ATP1A3 ChildhoodAlternating (i.e., from one side of the body to the other) attacks of dystonia w/a typical rostrocaudal distribution that may be triggered by fever, trauma, or stress
AD /
Dyskinesias		Benign hereditary chorea (See NKX2-1-Related Disorders.) NKX2-1 Childhood
  • Non-progressive choreiform movements
  • Severely affected persons can be disabled by the chorea.
XL & AR /
Dyskinesias		Pyruvate dehydrogenase deficiency (See Primary Pyruvate Dehydrogenase Complex Deficiency Overview.)ManyChildhood
  • Paroxysmal attacks of dystonia & chorea often in the form of PED
  • Attacks can be isolated or assoc w/signs & symptoms of Leigh syndrome.

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; MOI = mode of inheritance; PED = paroxysmal exercise-induced dyskinesia; XL = X-linked

1.

Heterozygous pathogenic variants in PRRT2 have been reported as causative of familial paroxysmal kinesigenic dyskinesia (PKD) in a subset of persons. The other gene(s) associated with PKD have not been identified.

From: Familial Paroxysmal Nonkinesigenic Dyskinesia

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