Publication Details

Title :

The Landscape of Early Infantile Epileptic Encephalopathy in a Consanguineous Population

Journal:

Seizure

Impact Factor:

2.765

Authors:

Nashabat M1, Al Qahtani XS2, Almakdob S3, Altwaijri W4, Ba-Armah DM4, Hundallah K2, Al Hashem A5, Al Tala S6, Maddirevula S7, Alkuraya FS8, Tabarki B2, Alfadhel M9.

Affiliations:

1 King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.

2 Division of Pediatric Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

3 College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

4 Division of Pediatric Neurology, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.

5 Division of Genetics, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

6 Division of Genetics, Department of Pediatrics, Armed Forces Hospital, Khamis Mushayt, Saudi Arabia.

7 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

8 Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

9 King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.

Year of Publication:

2019

DOI:

10.1016/j.seizure.2019.04.018.

Abstract:

PURPOSE:
Epileptic encephalopathies (EE), are a group of age-related disorders characterized by intractable seizures and electroencephalogram (EEG) abnormalities that may result in cognitive and motor delay. Early infantile epileptic encephalopathies (EIEE) manifest in the first year of life. EIEE are highly heterogeneous genetically but a genetic etiology is only identified in half of the cases, typically in the form of de novo dominant mutations.

METHOD:
This is a descriptive retrospective study of a consecutive series of patients diagnosed with EIEE from the participating hospitals. A chart review was performed for all patients. The diagnosis of epileptic encephalopathy was confirmed by molecular investigations in commercial labs. In silico study was done for all novel mutations. A systematic search was done for all the types of EIEE and their correlated genes in the literature using the Online Mendelian Inheritance In Man and PubMed databases.

RESULTS:
In this case series, we report 72 molecularly characterized EIEE from a highly consanguineous population, and review their clinical course. We identified 50 variants, 26 of which are novel, causing 26 different types of EIEE. Unlike outbred populations, autosomal recessive EIEE accounted for half the cases. The phenotypes ranged from self-limiting and drug-responsive to severe refractory seizures or even death.

CONCLUSION:
We reported the largest EIEE case series in the region with confirmed molecular testing and detailed clinical phenotyping. The number autosomal recessive predominance could be explained by the society’s high consanguinity. We reviewed all the EIEE registered causative genes in the literature and proposed a functional classification.