Intellectual Function of Patients with Epilepsies Related to De Novo Mutations
Abstract number :
3.269
Submission category :
6. Cormorbidity (Somatic and Psychiatric)
Year :
2022
Submission ID :
2204615
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:25 AM
Authors :
Kyoungmin Lee, MD – Severance hospital, yonsei university; Heung dong Kim, MD, Ph.D – Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Joon Soo Lee, MD, Ph.D – Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Hoon Chul Kang, MD, Ph.D – Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Se Hee Kim, MDMD, Ph.D – corresponding, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Rationale: An increasing number of patients with drug-resistant epilepsies are being identified to have a genetic abnormality. Neurodevelopmental disorders occur commonly in these patients. However, frequencies and concomitance of neurodevelopmental disorders in these patients remain to be investigated.
Methods: We evaluated 957 patients with epilepsy who underwent epilepsy or neurodevelopmental gene panels at Severance Hospital between January 2016 and December 2019. We identified 310 patients with genetic abnormalities. Of 310 patients, 147 underwent standardized instruments for cognition evaluation including Bayley Scales of Infant and Toddler Development (BSID), Wechsler Primary and Preschool Scale Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC), and Wechsler Adult Intelligence Scale (WAIS).
Results: Of 147, 90 (61.2%) were male. Median age at testing was 3.4 years old (interquartile range, 1-5). Fifteen patients had abnormal copy number variants while the rest had abnormal single nucleotide variants. BSID was the most commonly used test (112, 76.2%), followed by WISC (17, 11.5%), WPPSI (15, 10.2%), and WAIS (3, 2.0%). Overall, 36.7% (54) of the patients received the test more than once. _x000D_
In BSID, only 10 (8.9%) patients were normal development, and 10 (8.9%) patients of 122 were mild delayed, 92 (82.1%) patients were significantly delayed at the time of their first test. In Wechsler test, only 5 patients (10.2%) had normal cognition. Borderline intellectual functioning (BIF) was noted in 4 (11.4%) patients. 5 (14.3%) had mild ID, 12 (34.3%) had moderate ID, and 9 (25.7%) had severe/profound ID. Patients who showed normal cognition on their initial test had abnormal variants in genes including SCN1A, SCN8A, CHRNA4, GABRA1, KCNQ2, MBD5, PCDH19, and STXBP1. Patients who showed ID had abnormal variants in genes including SCN1A, SLC2A1, STXBP1, SCN2A, PCDH19, KCNQ2, CDKL5 and CHD2. All of the patients with pathogenic variants in CDKL5 (6/6), and CHD2 (6/6) had ID while 43% (3/7) of the patients with PCDH19 had ID. Majority of the patients with pathogenic variants in the following genes had ID: SLC2A1 (89%, 8/9) SCN2A (88%, 7/8), KCNQ2 (86%, 6/7).
Conclusions: Concomitant intellectual disability (ID) is common in patients who have de novo mutations related to developmental epileptic encephalopathies. An accurate identification of neurodevelopmental disorders is crucial for optimal clinical management in this patient group.
Funding: None
Cormorbidity (Somatic and Psychiatric)