Studying epilepsy and the rare CRMCC disorder
The research group of Pediatric Neurologist Tarja Linnankivi maps out gene mutations causing epilepsy. The group is also searching for ways to more rapidly identify CRMCC, a rare disorder affecting multiple organs. The studies used the most recent methods of genetic research.
The group operating in the Epilepsy Unit of New Children’s Hospital examines the genetic factors related to epilepsy in a joint project with the research group of Professor Anna-Elina Lehesjoki (Folkhälsan Research Center and Helsinki University). The cooperation began as early as the 1990s, when the first epilepsy genes were identified.
The study gathers information on the nature, treatment response and prognosis for epilepsies caused by various gene defects.
Linnankivi’s research group is oriented towards an active international cooperation, which is particularly important when studying rare epilepsy syndromes. Among other things, the group is involved in the world’s largest genetic epilepsy research project, the EPI25 study.
– The more than 60 children involved in the research project have been assigned a specific genetic diagnosis. It is important to determine the genetic cause, since it may affect the selection of the correct pharmaceutical treatment of epilepsy or other form of treatment, and it may also allow for accurate genetic counselling. In the long term, understanding the genetic backgrounds creates potential for developing targeted treatments for various forms of the disease, Tarja Linnankivi says.
The mystery of CRMCC
Linnankivi’s research group also delves into the mystery of CRMCC (cerebroretinal microangiopathy with calcifications and cysts), a rare disorder affecting multiple organs.
The disorder with abnormalities of the micro blood vessels of the brain and the retina involves the development of calcifications and cavities in the brain.
In Finland, CRMCC is more prevalent than elsewhere in the world. The symptoms and findings related to the disorder have been mapped out since the early 21st century.
– Subsequently, it has been discovered that the disorder affects multiple organs. In addition to the findings in the brain and the eyes, it is associated with a fetal growth defect, and abnormal skeletal structure, intestinal bleeding and blood count abnormalities, Linnankivi explains.
The research group discovered the CTC1 gene defect causing the disorder in 2012, simultaneously with a British research group.
The disorder is recessively hereditary and is often manifested in childhood, but milder forms of the disorder, in which the symptoms begin in adulthood, have also been discovered.
– Several manifestations of the disorder, such as blood count abnormalities as well as liver and kidney malfunctions, are not yet well known, and in these terms, our research continues.
Studies completed by the Linnankivi group help identify CRMCC more rapidly, which allows for better prevention of the damage caused, such as the loss of vision. The long-term goal is to slow down the progress of the disorder.
The CRMCC project includes experts in pediatric neurology, many other pediatric fields and imaging. There is also close cooperation with the research group of Professor Tero Kivelä from the Department of Ophthalmology (Eye Diseases) , and in terms of adult patients, with the research group of Hematologist, Docent Ulla Wartiovaara-Kautto. The research group of Professor Anna-Elina Lehesjoki (Folkhälsan Research Center and Helsinki University) is in charge of molecular genetic studies.
Helsinki University Hospital Children and Adolescentstarja.linnankivi(a)hus.fi
Links to genetic studies on epilepsy:
Defining the phenotypic spectrum of SLC6A1 mutations. Epilepsia. 2018 Feb;59(2):389-402. doi: 10.1111/epi.13986.
Dravet syndrome: New potential genetic modifiers, imaging abnormalities, and ictal findings. Epilepsia. 2013 Sep;54(9):1577-85. doi: 10.1111/epi.12256.
SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain Neurology. 2010 Oct 19;75(16):1454-8. doi: 10.1212/WNL.0b013e3181f8812e.
Links to CRMCC studies:
Cerebroretinal microangiopathy with calcifications and cysts. Neurology 2006;67;1437-1443.
Cerebroretinal microangiopathy with calcifications and cysts: characterization of the skeletal phenotype. Am J Med Genet A. 2011 Jun;155A(6):1322-8. doi: 10.1002/ajmg.a.33994.
Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am J Hum Genet. 2012 Mar 9;90(3):540-9. doi: 10.1016/j.ajhg.2012.02.002.