Objective: We describe a patient who presented to our movement disorder center for unilateral dystonic spells which last seconds and triggered by sudden movements. Genetic testing revealed a novel missense variant in NBEA. Clinical course and response to treatments are discussed. Video segment of the patient is included.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder where paroxysms of dyskinesias (dystonia, chorea, or combination) are triggered by sudden movements. Attacks tend to be short (seconds) and occur numerous times per day without loss of consciousness. Between attacks, examination is normal. Treatment with carbamazepine leads to complete abatement of the attacks. The most common genetic cause of PKD are variants in PRRT2. Other causative genes include SLC2A1, TMEM151A, CLCN1, KCNA1, and SCN8A. NBEA was recently proposed as a candidate PKD gene in a single family with a mother and daughter with PKD.

Method: A 15-year-old boy presented for evaluation of recurrent attacks of abnormal movements. At 12 years of age, he developed episodic posturing of his right arm with extension and pronation. After a few months, the posturing then spread to the leg and trunk. Initially these occurred around eight times per day, however, increased in frequency (too many to count). These episodes lasted 5-10 seconds. Triggers included sudden movements. Prior to an attack, there is a sensation of muscle tension. There is a 20-minute refractory period. There is no personal or family history of seizures, developmental delays, or intellectual disability nor family history of PKD. Neurologic examination between attacks was normal.

Results: The patient was treated with carbamazepine (600 mg BID) which was helpful, however developed drug related rash and discontinued. Levetiracetam was tried up to 2000 mg twice daily, which lead to mild reduction of attacks. He was then switched to oxcarbazepine (1200 mg BID) which led to complete control of attacks. Research trio exome sequencing revealed a de novo missense variant in NBEA(NM_001385012.1):c.6536A>C (p. Tyr2179Ser), chr13:35472487-A-C (hg38). The variant is absent from gnomAD and ClinVar. CADD score is 25.7 and involves a well-conserved amino acid.

Conclusion: This case highlights that NBEA should be considered in cases of PRRT2 negative PKD and can be treated with oxcarbazepine.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/paroxysmal-kinesigenic-dyskinesia-caused-by-a-novel-missense-variant-in-nbea/