STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy

Stamberger, Hannah; Nikanorova, Marina; Willemsen, Marjolein H; Accorsi, Patrizia; Angriman, Marco; Baier, Hartmut; Benkel-Herrenbrueck, Ira; Benoit, Valérie; Budetta, Mauro; Caliebe, Almuth; Cantalupo, Gaetano; Capovilla, Giuseppe; Casara, Gianluca; Courage, Carolina; Deprez, Marie; Destrée, Anne; Dilena, Robertino; Erasmus, Corrie E; Fannemel, Madeleine; Fjær, Roar; ... (2016). STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology, 86(10), pp. 954-962. Lippincott Williams & Wilkins 10.1212/WNL.0000000000002457

[img]
Preview
Text
954.full.pdf - Published Version
Available under License Publisher holds Copyright.

Download (385kB) | Preview

OBJECTIVE

To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients.

METHODS

We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients.

RESULTS

We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features.

CONCLUSION

De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Courage, Carolina, Lemke, Johannes

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0028-3878

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Anette van Dorland

Date Deposited:

02 May 2016 11:20

Last Modified:

05 Dec 2022 14:53

Publisher DOI:

10.1212/WNL.0000000000002457

PubMed ID:

26865513

BORIS DOI:

10.7892/boris.79345

URI:

https://boris.unibe.ch/id/eprint/79345

Actions (login required)

Edit item Edit item
Provide Feedback