Research Project: Genetic Basis of Familial HH
Principal Researchers: Prof Sam Berkovic and A/Prof. Michael Hildebrand
HH typically occurs in a single individual in a family and without clinical features outside of the brain. In such cases, genetic investigation of blood samples is usually unrevealing. That is because the changes that lead to the HH are confined to the brain. Consequently, the risk of other family members being affected is very low. Less commonly, HH occurs as a feature of disorders affecting other parts of the body as well; the best known is Pallister-Hall Syndrome (PHS). PHS is characterized by HH and additional features such as polydactyly (extra fingers or toes) and oral cavity malformations. PHS is a consequence of changes in the GLI3 gene that can be detected in blood or saliva samples, and the disorder runs in families. Our research suggests other genes may be involved as well and we are searching for these new causes in rare families with more than one individual with HH and individuals with PHS or PHS-like disorders negative for GLI3 on clinical testing.
Genetic testing is indicated for individuals with a clinical diagnosis of PHS or PHS-like disorder, as supported by evidence such as polydactyly or the oral cavity manifestations. These individuals are likely to have germline mutations in GLI3 which is detectable on standard genetic testing. We are interested in individuals with features of PHS where GLI3 has been excluded, although we would be interested to do the testing in families where there is more than one individual with HH and there is evidence of polydactyly, whether or not GLI3 has been tested for already. This testing would be provided free of charge on a research basis funded by our research grants, and individuals would receive the confidential testing results through their primary clinician and with genetic counselling available.
This research project aims to gain a better understanding of the mechanisms that cause HH and gelastic epilepsy in families, enabling us to develop and better target therapies for individuals and families with HH in the future.
Dr Hildebrand can be reached at:
Michael Hildebrand, PhD
Associate Professor
Head, Translational Neurogenetics Laboratory
Epilepsy Research Centre, Melbourne Brain Centre
Department of Medicine, University of Melbourne, Austin Health
245 Burgundy St. Heidelberg, Victoria, Australia 3084
Email: michael.hildebrand@unimelb.edu.au
Ph: + 61 3 9035 7143
Fax: + 61 3 9496 2291
