Objective: Describe a presentation of abnormal movements associated with a mutation in STXBP1.

Background: STXBP1, or the syntaxin binding protein 1 gene, is involved in neurotransmitter vesicle docking and fusion to the neuronal cell membrane. Mutations of STXBP1 are typically associated with epilepsy and early infantile epileptic encephalopathy (EIEE or Ohtohara Syndrome), and intellectual disability without epilepsy. In cohorts of patients with EIEE and STXBP1 mutations, abnormal involuntary movements have included head stereotypies, dystonia, ataxia, and tremulousness. In this case report, we describe a child who presented with a complex movement disorder without any history of seizures, who was found to have a mutation in STXBP1.

Methods: Case report and review of the literature.

Results: The subject was initially evaluated by the authors at the age of 7 years. He had a history of poor cry, diminished spontaneous movement, and low tone at birth, with subsequent global developmental delay. At the age of 7 months, he developed involuntary semi-rhythmic movements of all extremities. At the time of evaluation, he had no spontaneous speech, and was unable to sit unsupported or maintain posture. Examination was notable for a head tremor, persistent bilateral upper extremity myoclonus at rest that worsened with action, and dystonic posturing of the lower extremities. Family history was unremarkable. Prior work up included an initial MRI interpreted as having possible posterior white matter changes and delayed myelination, however, a repeat MRI and MRS were normal. EEG showed slow delta-theta activity and high voltage paroxysms that did not correspond to any of the observed abnormal movements. Metabolic testing included normal CSF neurotransmitters, plasma amino acids, urine organic acids, ceruloplasmin, and lactate. PANK2 genetic testing was negative. Whole exome sequencing was pursued and a novel, heterozygous variant, c.1439C>T (p.P480L) was identified within the STXBP1 gene. This change was predicted to be pathogenic and was not found in other family members tested.

Conclusions: STXBP1 mutations should be considered in the differential diagnosis of children with movement disorders and developmental delay, even in the absence of a clinical history of epilepsy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dystonia-myoclonus-and-tremor-without-epilepsy-associated-with-a-mutation-in-stxbp1/