Abstract Details

Title Periodic Paralysis in the Phenotypic Spectrum of CLCN1 Gene Mutation

Topic Child Neurology and Developmental Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-048

Objective We report a child, with periodic paralysis, who tested positive for a mutation in CLCN1. Mutations in CLCN1 gene have typically associated with a myotonia congenital phenotype.

Background

Hypokalemic periodic paralysis is typically associated with mutations in voltage-dependent calcium channel (CACNA1S) and voltage-gated sodium channel (SCN4A) genes.

Design/Methods Case Report

Results An 11-year old male with a family history of his mother having similar symptoms initially presented at 3 years of age with episodes of periodic paralysis lasting a few hours to all day. Weakness typically starts in the legs and progresses to the arms and neck and is associated with documented bouts of hypokalemia consistent with hypokalemic periodic paralysis. Initial genetic testing for CACNA1S and SCN4A was negative. NCS/EMG was normal, except for an abnormal long exercise test with augmentation of 69% in amplitude and augmentation of 114% in area after 5 minutes of maximal exercise. This suggested a pre-synaptic disorder of neuromuscular transmission without any features of myotonia. Additional genetic testing for hypo/hyperkalemic periodic paralysis revealed a heterozygous pathogenic mutation in CLCN1 (c.568_569delGGinsTC). He was treated with potassium supplementation during acute periods of weakness and acetazolamide as preventive therapy without any effect.

Conclusions

CLCN1 mutations typically associate with myotonia congenita. Our patient has features of hypokalemic periodic paralysis, but no myotonia on examination or EMG. This suggests periodic paralysis may be in the phenotypic spectrum of CLCN1 mutations. We are unaware of other reports of hypokalemic periodic paralysis associated with CLCN1 mutations.

Authors/Disclosures
Himadri Patel, MD (UPMC Neurology) PRESENTER	No disclosure on file
Harmanpreet Tiwana, MD	No disclosure on file
Gayatra Mainali, MD (Penn State Health)	Dr. Mainali has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Origin Biosciences.
Matthew P. Wicklund, MD, FAAN (UT Health San Antonio)	Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics. Dr. Wicklund has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Wicklund has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Wicklund has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Spark Therapeutics. Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ultragenyx. Dr. Wicklund has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmaceuticals. The institution of Dr. Wicklund has received research support from Orphazyme. The institution of Dr. Wicklund has received research support from Muscular Dystrophy Association. The institution of Dr. Wicklund has received research support from Coalition to Cure Calpain 3. The institution of Dr. Wicklund has received research support from Sarepta Therapeutics. The institution of Dr. Wicklund has received research support from ML Bio. The institution of Dr. Wicklund has received research support from Alexion. The institution of Dr. Wicklund has received research support from Acceleron. The institution of Dr. Wicklund has received research support from Edgewise. The institution of Dr. Wicklund has received research support from Fulcrum. The institution of Dr. Wicklund has received research support from Roche-Genentech. The institution of Dr. Wicklund has received research support from Avidity. Dr. Wicklund has received research support from Harmony Bioscience.
Ashutosh Kumar, MD (Penn State Health)	Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC therapeutics. Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Kumar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Kumar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Kumar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Kumar has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for PTC therapeutics. Dr. Kumar has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for American Academy of Pediatrics. The institution of Dr. Kumar has received research support from PTC therapeutics. The institution of Dr. Kumar has received research support from Sarepta Therapeutics. The institution of Dr. Kumar has received research support from Novartis/Avexis. The institution of Dr. Kumar has received research support from Fibrogen . The institution of Dr. Kumar has received research support from Biohaven. The institution of Dr. Kumar has received research support from Genentech. The institution of Dr. Kumar has received research support from MDA. Dr. Kumar has received personal compensation in the range of $500-$4,999 for serving as a Draft Report Reviewer/consultant with ECRI/Atheneum/QTC commercial services LLC/Connected Research and consulting/Vox.Bio.

��ɫ��

��ɫ��