Author/Editor		Gradišnik, Peter
Title		Pregled monogensko dedovanih epilepsij
Translated title		Review of monogenic inherited epilepsies
Type		članek
Source		In: Bolezni in simptomi otrok kot odraz slabega družinskega ravnotežja Genetika v pediatriji Zastrupitve pri otrocih : zbornik predavanj Maribor : Univerzitetni klinični center
Publication year		2013
Volume		str. 77-82
Language		slv
Abstract		Mednarodna zveza proti epilepsiji (angl. International League Against Epilepsy, ILAE) svetuje, da starejši izraz idiopatska epilepsija nadomestimo z izrazom genetska epilepsija. Epidemiološki dokazi namreč kažejo, da epilepsijo, ki ni posledica bodisi strukturne ali presnovne okvare, povzroča genetska nagnjenost. Ta je vzrok za epilepsijo pri skoraj polovici bolnikov. Genetsko povzročene epilepsije se večinoma dedujejo poligensko. Monogenskih epilepsij je malo, približno 2 % genetsko povzročenih epilepsij. Kljub temu pa so izjemno pomembne, saj jih je lažje preučevati ter tako prepoznati in razumeti patofiziološka dogajanja, ki vodijo do epileptogeneze. Mutacije, ki jih povzročajo, so odkrili šele v zadnjih dveh desetletjih, mnoge šele v zadnjih nekaj letih. Večinoma te mutacije spreminjajo strukturo beljakovin, ki so sestavni deli ionskih kanalčkov živčnih celic, in povzročajo večjo vzdražnost živčnih celic. Opisujejo tudi mutacije, ki najverjetneje vplivajo na pravilno zamreženje nevronskih povezav. Domnevamo, da so mehanizmi epileptogeneze pri epilepsijah, ki se dedujejo poligensko, podobni. To domnevo podpira tudi ugotovitev, da v nekaterih redkih primerih pri posameznih družinah s poligensko dedovanimi epilepsijami enako klinično sliko povzroča ena sama, monogensko dedovana mutacija. V prispevku opisujemo monogensko dedovane epilepsije, ki so pomembne zaradi relativne pogostosti pojavljanja ali specifičnega mehanizma epileptogeneze. Odkritja na področju genetike epilepsij nam lahko olajšajo razvrstitev epilepsij, pravilno napoved izida bolezni in ustrezno svetovanje bolnikom oziroma njihovim staršem. V prihodnosti pa nam bodo lahko v pomoč pri ciljanih terapevtskih pristopih.The International League against Epilepsy (ILAE) has advised replacing the older term idiopathic epilepsies with the new concept of genetic epilepsies. Epidemiological evidence shows that epilepsy not caused by either structural or metabolic defects, is caused by genetic predisposition. This is the cause of epilepsy in almost half of epileptic patients. The pattern of inheritance in genetic epilepsies is mostly polygenic. Only about two per cent of genetic epilepsies have a monogenic mode of inheritance. However, they are important as they are easier to study and thus to understand the pathophysiologic mechanisms leading to epileptogenesis. The causative mutations have all been discovered only in the last two decades, many of them only in the last few years. The majority of these mutations alter the structure of proteins, which are components of neuronal ion channels. The result of such mutations is increased neuronal excitability. Mutations that probably affect the correct formation of neural networks have also been described. The epileptogenic mechanisms in the majority of genetic epilepsies that have a polygenic mode of inheritance are presumed to be similar. This supposition is supported by the finding that, in some individual families, epilepsies that are known to generally have a polygenic mode of inheritance evolve with the same clinical picture as that caused by a single, monogenic mutation. This paper describes some of the monogenic epilepsies, which are important either because of their relative frequency or their specific epileptogenic mechanisms. Discoveries in the field of the genetics of epilepsy can improve the classification of epilepsies, facilitate the correct prognosis and counselling of patients and their families, and may lead to targeted therapeutic approaches in the future.
Descriptors		Epilepsy Epilepsija Child Otrok Genetics Genetika