Abstract
BackgroundIsodicentric 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.Case presentationWe 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.DiscussionAs 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.ConclusionAs 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.
Highlights
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
As her genetic testing confirmed that her region of duplication included gamma-aminobutyric acid (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
We report severe paradoxical worsening of epilepsy in an adult woman with IDIC-15 with complex partial seizures and secondary generalization who had been treated with Pregabalin and a dramatic improvement after the drug was discontinued
Summary
This case suggests that pregabalin and possibly other GABA analogs or gabaergic drugs should be used cautiously in individuals with IDIC- as the abnormal GABA receptor configuration and physiology could alter the pharmacological response to the drugs. Lacosamide, and presumably other ionic pump inhibitors may instead be safer and more effective in subjects with IDIC-15. This case indirectly illustrates that people with IDIC-15 can maintain a stable level of neurological and intellectual function well into mature age if seizures are controlled. Authors’ contributions ADR: study concept, manuscript preparation. MDR: genetic component of the study report and analysis. Author details 1New York University School of Medicine, New York, NY, USA. Author details 1New York University School of Medicine, New York, NY, USA. 2University of Genoa School of Medicine, Genoa, Italy. 3Giannina Gaslini Institute, Genoa, Italy. 4Formerly Giannina Gaslini Institute, Genoa, Italy. 5Robert Wood Johnson School of Medicine and Johnson Rehabilitation Institute, Edison, NJ, USA. 6Columbia University College of Physicians and Surgeons, New York, NY, USA. 7Department of Neurology, NYU Langone Medical Center, New York University School of Medicine, 145 E 32nd Street, New York, NY 10016, USA
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