title: Chromosome 9q33q34 microdeletion with early infantile epileptic encephalopathy, severe dystonia, abnormal eye movements, and nephroureteral malformations.
abstract: BACKGROUND
  Microdeletion of chromosome 9q33q34 is an emerging disease disorder associated with early infantile epileptic encephalopathy, intellectual disability, and a variety of movement disorders.
  
  
  METHODS
  We describe a male infant with early infantile epileptic encephalopathy with suppression-burst (Ohtahara syndrome) who carried a de novo 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 novo 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.
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan. Electronic address: matumoto@ndmc.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Zaha
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
mesh_terms: D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D019465:Craniofacial Abnormalities / Q000150:complications* / Q000175:diagnosis; D004421:Dystonia / Q000209:etiology*; D004569:Electroencephalography; D006330:Heart Defects, Congenital / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications* / Q000175:diagnosis; D008279:Magnetic Resonance Imaging; D008297:Male; D009404:Nephrotic Syndrome / Q000209:etiology*; D015835:Ocular Motility Disorders / Q000209:etiology*; D013036:Spasms, Infantile / Q000175:diagnosis / Q000209:etiology*
keywords: 9q33q34 microdeletion; STXBP1; dystonia; early infantile epileptic encephalopathy; nephroureteral malformations; nystagmus