Paroxysmal Hypotonia in PRRT2-Related Paroxysmal Diseases

A 5-year-old girl had a 2-week history of episodic weakness characterized by blank staring and profound hypotonia (with preserved visual tracking but impaired phonation), or unilateral limb weakness (with preserved speech) (Video 1), lasting seconds to 2 hours and occurring multiple times daily without clear triggers.EEG and brain MRI/MRA were normal.Therapeutic trials showed no improvement with placebo, but marked improvement with oxcarbazepine.TRIO-WES revealed a pathogenic heterozygous PRRT2 variant (c.649dupC/p.Arg217ProfsTer8).Family history revealed maternal febrile seizures and SeLIE/PKD in relatives (eFigure 1).Symptoms resolved on oxcarbazepine, recurred off-medication, and were controlled on reinitiation.PRRT2-related movement disorders consistently manifest as dystonia/choreoathetosis. 1,2Although PRRT2-related familial hemiplegic migraine may present with abrupt unilateral weakness, 1 our case is distinct in demonstrating recurrent, mainly generalized, profound hypotonia, without headache/aura.Paroxysmal hypotonia represents a novel and clinically distinct phenotype within the PRRT2-related spectrum, supported by diagnostic exclusion, treatment response, and genetic segregation, highlighting phenotypic variability even with identical hotspot variants.