title: Paroxysmal tonic upward gaze as a presentation of de-novo mutations in CACNA1A.
abstract: OBJECTIVE
  Paroxysmal tonic upward gaze was initially described as a benign phenomenon with negative investigations and eventual complete resolution of symptoms. Later publications demonstrated that a similar clinical picture may arise from structural brain lesions, channelopathies, neurotransmitter disorders, and epileptic seizures. CACNA1A related disorders manifest as a wide spectrum of paroxysmal neurological disorders: episodic ataxia 2, hemiplegic migraine, benign paroxysmal torticollis of infancy, and paroxysmal vertigo. Paroxysmal tonic upward gaze as a phenomenon in patients with mutations in the CACNA1A gene has only been reported once.
  
  
  METHODS
  We describe three patients with multiple episodes of paroxysmal tonic upward gaze that appeared during the first months of life. In addition the patients demonstrated motor and language delay and cerebellar ataxia. A sequence analysis of the CACNA1A gene in one patient and whole exome sequencing in the other patients were performed.
  
  
  RESULTS
  Sequence analysis of the CACNA1A gene in one patient and whole exome sequencing in the two other patients revealed 3 different de-novo mutations in the CACNA1A gene.
  
  
  CONCLUSIONS
  CACNA1A mutations should be evaluated in infants and young children with paroxysmal tonic upgaze especially if associated with developmental delay, cerebellar signs, and other types of paroxysmal event.
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel. Electronic address: luba.blumkin@gmail.com.
authors.forename: Lubov
authors.initials: L
authors.lastname: Blumkin
authors.affiliation: Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Molecular Laboratory, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.affiliation: Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Michelson
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Zerem
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel; Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv University, Holon, Israel.
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009422:Nervous System Diseases / Q000150:complications* / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000209:etiology* / Q000235:genetics*; D014717:Vertigo / Q000209:etiology / Q000235:genetics; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: Ataxia; CACNA1A; Paroxysmal tonic upward gaze