Abstract Details

Title Diversity of Epilepsy and Movement Disorder Phenotypes in STXBP1 Mutations

Topic Child Neurology and Developmental Neurology

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

Poster/Presentation
Number 7-046

Objective To describe the phenotypic variability of children with STXBP1mutations.

Background Found at chromosome 9q34.11,STXBP1encodes syntaxin-binding protein 1, which is responsible for vesicle fusion and highly expressed in the brain. Classically, heterozygous STXBP1mutations were associated with early infantile epileptic encephalopathy (EIEE). Developmental and movement disorders are less frequently reported. Approximately 200 patients are described and fewer than 25% presented with a movement disorder, with dystonia in less than 20% of those. Behavioral disorders are also described in fewer than 25% of affected individuals.

Design/Methods NA

Results We present three patients with STXBP1mutations and widely variable clinical presentations. Patient 1 presented with Ohtahara Syndrome at 5-days of age, consistent with the classic EIEE phenotype. Spasticity with prominent dystonia and opisthotonos developed as a neonate with frequent dystonic crises, necessitating ICU care. A missense mutation was found in exon 16 on a multi-gene epilepsy panel at 2-weeks of age. The patient succumbed to respiratory failure at 21-months. Patient 2 presented at 3-days of age with a milder epileptic phenotype that has been controlled on monotherapy. At age 17-months, she has mild developmental delay, but no signs of movement disorder. A 217-kb interstitial deletion at 9q34.11 was identified on chromosomal microarray at 3-weeks of age. Patient 3 was diagnosed with cerebral palsy at 12-months despite no suggestive perinatal history and non-specific gliosis on MRI. She has intellectual disability with autistic features and aggression, ataxia, and a disabling tremor of her upper extremities. She had three febrile seizures as a toddler. A non-sense mutation in exon 11 was identified on whole exome sequencing at 10-years of age.

Conclusions These cases represent the phenotypic variability of STXBP1mutations beyond the classic EIEE presentation. A diagnosis of STXBP1should be considered in patients with infantile-onset movement disorders or unexplained cerebral palsy.

Authors/Disclosures
Darrah Haffner, MD (Nationwide Children's Hospital) PRESENTER	Dr. Haffner has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Naiser Law Office.
Kimberly Goodspeed, MD (University of Texas Southwestern Medical Center)	The institution of Dr. Goodspeed has received research support from Neurogene, Inc.

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