Clinical characteristics: STXBP1 encephalopathy with epilepsy is characterized by early-onset developmental delay, intellectual disability or cognitive dysfunction, and epilepsy. The median age of onset of seizures is six weeks (range: 1 day to 13 years). Seizure types can include infantile spasms; generalized tonic-clonic, clonic, or tonic seizures; and myoclonic, atonic, absence, and focal seizures. EEG abnormalities can include focal epileptic activity, burst suppression, hypsarrhythmia, or generalized spike-and-slow waves. Other neurologic findings include abnormal tone, movement disorders (especially ataxia and dystonia), and behavioral issues and autism spectrum disorder. Feeding difficulties are common.
Diagnosis/testing: The diagnosis is established in a proband with a heterozygous STXBP1 pathogenic variant identified by molecular genetic testing.
Management: Treatment of manifestations: Standard treatments for developmental, cognitive, and neurobehavioral issues. The most commonly used anti-seizure medications (ASMs) are phenobarbital, valproic acid, and vigabatrin. About 20% of individuals require more than one ASM and approximately 25% are refractory to ASM therapy. Severe dystonia, dyskinesia, and choreoathetosis can be treated with monoamine-depleting or dopaminergic agents. Treatment per orthopedics, physical medicine and rehabilitation, physical therapy, and occupational therapy to help avoid contractures and falls, with positioning and mobility devices as needed. Feeding difficulties and constipation are managed per standard protocols. Social work support and care coordination as needed.
Surveillance: Monitor developmental progress and educational needs, seizures, changes in tone, movement disorders, behavioral issues, growth and nutritional status, evidence of constipation, and family needs at each visit; follow-up EEG as needed; occupational and physical therapy assessments as needed.
Genetic counseling: STXBP1 encephalopathy with epilepsy is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Most individuals reported to date represent simplex cases (i.e., the only family member known to be affected) and have the disorder as the result of a de novo STXBP1 pathogenic variant. Individuals with STXBP1 encephalopathy with epilepsy are not known to reproduce. Once the STXBP1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are available.
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