LAUSR

KCNMA1 codes for the pore-forming alpha-subunit of the voltageand calcium-sensitive potassium channel (BK channel). BK channel dysfunction has previously been implicated in paroxysmal dyskinesia. We describe 3 unrelated patients with cataplexy, all sharing the same KCNMA1 gene mutation identified by whole exome sequencing (KCNMA1 [NM_002247.3] c.2984 A > G [p.N999S]), previously described as conferring a gain of function and reported in patients with paroxysmal dyskinesia and developmental delay phenotype. Parents do not harbor the mutation and are asymptomatic. Patient 1 has an additional variant in the KCNMA1 gene (c.3382 C > T [p.Arg1128Trp]) predicted to be benign. Patient 1 is a 4-year-old female with cataplexy (Video S1), hypotonia, and global developmental delay, conceived via sperm donor (neither KCNMA1 variant is maternally inherited, father’s genotype is unknown). MRI brain was normal. No signs of narcolepsy were evident and CSF hypocretin-1 was normal (425.5 pg/mL). Clonazepam, amitriptyline, and levetiracetam were ineffective. Initiation of acetazolamide and docosahexaenoic-acid subjectively reduced cataplexy and the acetazolamide’s efficacy was supported by an n = 1 trial (Fig. 1). A reduction in the frequency of cataplexy was associated with parallel neurodevelopmental progress. Patient 2 is a 6-year-old female with cataplexy (Video S2), global developmental delay, and absence seizures. Diagnostic evaluation for narcolepsy and Niemann-Pick C were all unrevealing. Absence seizures began at age 6 years. She has about 12 cataplexy events daily, as well as dozens of absence seizures daily. She has not tried any medication at the time of this submission. Patient 3 is a 12-year-old male with cataplexy (Video S3), intellectual disability, autism spectrum disorder, speech and FIG 1. (A) number of episodes recorded manually daily by caregivers of patient 1 during acetazolamide dosage increases (+), decreases (−), and washout (Ø). (B) Decreased number of episodes with acetazolamide treatment. Number of days indicated/dosage. *P < 0.05 Mann–Whitney test.