Epilepsy is not a mandatory feature of STXBP1 associated ataxia-tremor-retardation syndrome

Original research article by Gburek-Augustat et al. (2016).

Read the abstract here.

The STXBP1 gene is associated with signaling pathways in the brain, and in the past, genetic changes (mutations) in the STXBP1 gene were commonly associated with early infantile epileptic encephalopathy (EIEE), an epileptic condition characterized by frequent seizures and spikes in EEGs (electroencephalograms) within the first few months of life. This condition is referred to as Ohtahara syndrome. Over time, changes in the STXBP1 gene were recognized in individuals with other forms of epilepsy, as well as in individuals with intellectual disability (ID) and movement disorders without a history of epilepsy.

This recent study by the Gburek-Augustat research team identified three unrelated females (“Patient I”: age 12, “Patient II”: age 11, and “Patient III”: age 9) with de novo STXBP1 mutations, meaning their mutations were not found to be inherited from their parents. Patient I was identified through whole-exome sequencing; Patient II was identified using a ID genetic testing panel; and Patient III was referred to the researchers by Patient II’s parents because of their similar features. All three girls had ID and severe developmental delay (DD), as well as similar clinical features. While no epilepsy or abnormal brain MRIs or EEGs were reported in any of the patients, the following features were reported in all three patients: ID, DD, low muscle tone (hypotonia), psychomotor delay, action tremors of arms and hands, coordination issues (ataxia), and limited speech abilities. Interestingly, the ID and DD reported in each patient was not as severe as individuals who do have EIEE.

Previously, the STXBP1 gene was primarily considered as a potential diagnosis for patients with epilepsy. While most individuals found to have a mutation in STXBP1 do have epilepsy, this research shows that it is possible for changes in this gene to be found in individuals without epilepsy. This suggests that that epilepsy should not be considered a mandatory feature of individuals with a STXBP1 mutation and that testing should be expanded and performed in those individuals who have ID/DD, hypotonia, language issues, ataxia, and tremors without epilepsy.

New technologies and research are helping us learn more about genetic diseases, causes, and symptoms every day. Many of these developments would not be possible without participation in research projects. Thank you to our Simons Searchlight families who are allowing us to gain more information on genetic changes that may lead to future developments of our own.