Abstract Details

Title Neurobehavioral Issues in the Phenotypic Spectrum of Variations in OTX2

Topic Child Neurology and Developmental Neurology

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

Poster/Presentation
Number 7-043

Objective The majority of pathogenic variants in the OTX2 gene have been reported in the patients with ocular malformation, pituitary dysfunction with growth hormone deficiency and rarely patients with neurological issues such as developmental delay, learning disabilities, behavioral problems or seizure.

Background

We describe a 7-year-old boy with varied neurological presentation found to have two variants in OTX2 which may be related to his phenotype.

Design/Methods Case Report

Results The proband initially presented at 5 years of age for evaluation of periodic dystonia and ataxia. His birth history and family history was unknown as he was adopted but he had short stature, developmental delay with autistic feature and perseveration, failure to thrive, hypotonia, dysarthria, titubation, unsteadiness, tremors, recurrent vomiting, OSA, periodic dystonia and ataxia. MRI of his brain showed thinning of splenium of the corpus callosum, hypoplasia of pituitary gland with ectopic posterior pituitary and a Dandy-Walker variant with prominent fourth ventricle and cisterna magna. 16 gene dystonia panel was negative. Whole exome sequencing showed two variants in OTX2 in cis, p.L61R and p.R69W. He is presently doing well on oxcarbazepine and lamotrigine for dystonia and behavioral issues.

Conclusions The OTX2 gene is implicated in the development of brain, eye, and the pituitary. Most of the patients reported have ocular abnormalities most commonly anophthalmia-microphthalmia, short stature due to growth failure from pituitary dysfunction and other neurological abnormalities. Our patient had no eye abnormality but he had pituitary hypoplasia and multiple neurological problems including hypotonia, dystonia, ataxia which has not been reported in the literature. His WES showed two cis-variants in OTX2 p.L61R and p.R69W,that is possibly related to his phenotype. These variants have not previously been reported but are predicted to have a detrimental effect. Our case is potentially expanding the phenotype seen in variations in OTX2.

Authors/Disclosures
Himadri Patel, MD (UPMC Neurology) PRESENTER	No disclosure on file
Harmanpreet Tiwana, MD	No disclosure on file
Mayur Chalia, MD	Dr. Chalia has nothing to disclose.
Melissa Yelton	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.
Gerald Raymond, MD (Johns Hopkins)	Dr. Raymond has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Bluebird bio. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Travere. Dr. Raymond has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with Dept of HHS.
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.

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