title: Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes.
abstract: BACKGROUND
  Isodicentric 15 syndrome (IDIC-15) is due to partial duplications of chromosome 15 that may includes the q11-13 region that includes genes encoding the α5 (GABRA5) and β3 - γ3 (GABRB3) receptor subunits. The disease causes intellectual and physical developmental delay, seizures, intellectual disability and behavioral disorders that may be related to abnormal GABA receptor function and morphology. Seizures are often severe and may be refractory to treatment. There are however no specific guidelines for the treatment of the seizures and it is unknown whether drugs that affect the GABAergic system have a different effect in IDIC-15 seizures.
  
  
  METHODS
  We report the case of an adult individual with IDIC-15 whose complex-partial seizures worsened dramatically after the introduction of pregabalin, with increased seizure frequency, frequent generalization, and appearance of new seizure pattern. Her cognitive function and verbal skills also worsened during treatment with pregabalin. Her seizures and cognitive skills quickly improved after pregabalin was discontinued and treatment with lacosamide started.
  
  
  CONCLUSIONS
  As her genetic testing confirmed that her region of duplication included GABA receptor encoding genes, it is plausible that the worsening of seizures were due to induction of an abnormal GABAergic response to pregabalin.
  
  
  CONCLUSIONS
  As her genetic testing confirmed that her region of duplication included GABA receptor encoding genes, it is plausible that the worsening of seizures were due to induction of an abnormal GABAergic response to pregabalin.This case may help define proper therapeutic strategies for the treatment of IDIC-15 associated seizures.
authors.affiliation: New York University School of Medicine, New York, NY, USA. alessandro.dirocco@med.nyu.edu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Rocco
authors.forename: Andrea
authors.initials: A
authors.lastname: Loggini
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Rocco
authors.forename: Roger P
authors.initials: RP
authors.lastname: Rossi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gimelli
authors.forename: Carl
authors.initials: C
authors.lastname: Bazil
mesh_terms: D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D011596:Psychomotor Disorders / Q000150:complications / Q000235:genetics*; D018079:Receptors, GABA / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D014314:Trisomy / Q000235:genetics*
chemical_list: D018079:Receptors, GABA