title: Genetics of reflex seizures and epilepsies in humans and animals.
abstract: BACKGROUND
  Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies.
  
  
  METHODS
  References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies.
  
  
  RESULTS
  Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in patients with symptomatic epilepsies but have also been reported in the setting chromosomal disorders or genetically inherited lysosomal storage diseases.
  
  
  CONCLUSIONS
  The genetic background of reflex seizures and epilepsies is heterogeneous and mostly unknown with no major gene identified in humans. The benefits offered by next-generation sequencing technologies should be merged with increasing information on animal models that represent an useful tool to study the mechanism underlying epileptogenesis. Finally, we expect that genetic studies will lead to a better understanding of the multiple factors involved in the pathophysiology of reflex seizures, and eventually to develop preventive strategies focused on seizure control and therapy optimization.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Italiano
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Viale Europa, Catanzaro, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Viale Europa, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, Messina, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.affiliation: Laboratory of Neurogenetics and Neurosciences, Department of Neurosciences, "G. Gaslini" Institute, Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.affiliation: Epilepsy Center, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Viale Europa, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Viale Europa, Catanzaro, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Regional Epilepsy Centre, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gasparini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 1, Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lamberti
authors.affiliation: Science of Health Department, School of Medicine, University of Catanzaro, Viale Europa, Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Viale Europa, Catanzaro, Italy; Regional Epilepsy Centre, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy. Electronic address: u.aguglia@tin.it.
authors.forename: Umberto
authors.initials: U
authors.lastname: Aguglia
authors.affiliation: Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Viale Europa, Catanzaro, Italy; Regional Epilepsy Centre, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Ferlazzo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000235:genetics*; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D012640:Seizures / Q000235:genetics*
keywords: Eating; Genes; Music; Photosensitivity; Reading; Startle