Anti-SPTAN1 monoclonal antibody, clone AA6 (7A3)

STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, is a gene causing epileptic encephalopathy. Mutations in STXBP1 have first been reported in early onset epileptic encephalopathy with suppression-bursts, then in infantile spasms and, more recently, in patients with non syndromic mental retardation without epilepsy. We analyzed clinical evolution and brain magnetic resonance imaging in 7 patients (6 females, 1 male) with early onset epileptic encephalopathies associated with STXBP1 mutations. We documented a peculiar brain MRI aspect characterized by frontal hypoplasia and a thin and dysmorphic corpus callosum. The course of the epilepsy was relatively benign. These clinical and neuroradiological features could orient the clinician in selecting patients' candidate to genetic testing for STXBP1 gene. (C) 2013 Elsevier Masson SAS. All rights reserved.

BACKGROUND: Microdeletion of chromosome 9q33q34 is an emerging disease disorder associated with early infantile epileptic encephalopathy, intellectual disability, and a variety of movement disorders. PATIENT: We describe a male infant with early infantile epileptic encephalopathy with suppression-burst (Ohtahara syndrome) who carried a de nova 2.0-Mb microdeletion in chromosome 9q33q34, including STXBP1. The previously reported examples of 9q33q34 microdeletion including STXBP1 are reviewed. RESULTS: The patient developed infantile spasms at 4 months of age, and these were refractory to multiple antiepileptic drugs. He also developed severe dystonia during infancy, rotatory nystagmus, and nephroureteral malformations. Immunoglobulin and clobazam administered at 11 months were effective for the spasms, but profound psychomotor retardation remained. A comparative genomic hybridization array analysis and the fluorescence in situ hybridization analysis revealed a de nova 2.0-Mb microdeletion in chromosome 9q33q34, which encompasses STXBP1, ENG, SPTAN1, and 52 other genes. A total of 14 patients (13 from the literature) with a 9q33q24 microdeletion including STXBP1 were reviewed, five of them displayed early infantile epileptic encephalopathy with suppression-burst, and six of them had early-onset epilepsy but not early infantile epileptic encephalopathy. Dystonia has been previously described in 9q33q34 deletions involving TOR1A but not STXBP1. Neither abnormal eye movements nor nephroureteral malformations has been previously described. CONCLUSIONS: This patient adds unique clinical presentations of neurological and nephroureteral abnormalities to the features of 9q33q34 microdeletion.