Landscape of genetic infantile epileptic spasms syndrome-A multicenter cohort of 124 children from India.

Autor: Nagarajan B; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Gowda VK; Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, India., Yoganathan S; Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, India., Sharawat IK; Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India., Srivastava K; Pediatric Neurology Unit, Department of Pediatrics, Bharati Vidyapeeth Deemed University Medical College, Pune, India., Vora N; Royal Institute of Child Neurosciences, Ahmedabad, India., Badheka R; Royal Institute of Child Neurosciences, Ahmedabad, India., Danda S; Department of Medical Genetics, Christian Medical College, Vellore, India., Kalane U; Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India., Kaur A; Genetics and Metabolic Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Madaan P; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.; Department of Pediatric Neurology, Amrita Institute of Medical Sciences, Faridabad, India., Mehta S; Royal Institute of Child Neurosciences, Ahmedabad, India., Negi S; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Panda PK; Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, India., Rajadhyaksha S; Pediatric Neurology Unit, Department of Pediatrics, Bharati Vidyapeeth Deemed University Medical College, Pune, India., Saini AG; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Saini L; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.; Department of Pediatrics, All India Institute of Medical Sciences, Jodhpur, India., Shah S; Royal Institute of Child Neurosciences, Ahmedabad, India., Srinivasan VM; Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, India., Suthar R; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Thomas M; Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, India., Vyas S; Division of Neuroimaging and Interventional Neuroradiology, Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Sankhyan N; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Sahu JK; Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Jazyk: angličtina
Zdroj: Epilepsia open [Epilepsia Open] 2023 Dec; Vol. 8 (4), pp. 1383-1404. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1002/epi4.12811
Abstrakt: Objective: Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce in developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children.
Methods: Between January 2021 and June 2022, this cross-sectional study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural-genetic and structural-metabolic etiology, were recruited and underwent detailed in-person assessment for phenotypic characterization. The multicentric data on the genotypic and phenotypic characteristics of genetic IESS were collated and analyzed.
Results: Of 124 probands (60% boys, history of consanguinity in 15%) with genetic IESS, 105 had single gene disorders (104 nuclear and one mitochondrial), including one with concurrent triple repeat disorder (fragile X syndrome), and 19 had chromosomal disorders. Of 105 single gene disorders, 51 individual genes (92 variants including 25 novel) were identified. Nearly 85% of children with monogenic nuclear disorders had autosomal inheritance (dominant-55.2%, recessive-14.2%), while the rest had X-linked inheritance. Underlying chromosomal disorders included trisomy 21 (n = 14), Xq28 duplication (n = 2), and others (n = 3). Trisomy 21 (n = 14), ALDH7A1 (n = 10), SCN2A (n = 7), CDKL5 (n = 6), ALG13 (n = 5), KCNQ2 (n = 4), STXBP1 (n = 4), SCN1A (n = 4), NTRK2 (n = 4), and WWOX (n = 4) were the dominant single gene causes of genetic IESS. The median age at the onset of epileptic spasms (ES) and establishment of genetic diagnosis was 5 and 12 months, respectively. Pre-existing developmental delay (94.3%), early age at onset of ES (<6 months; 86.2%), central hypotonia (81.4%), facial dysmorphism (70.1%), microcephaly (77.4%), movement disorders (45.9%) and autistic features (42.7%) were remarkable clinical findings. Seizures other than epileptic spasms were observed in 83 children (66.9%). Pre-existing epilepsy syndrome was identified in 21 (16.9%). Nearly 60% had an initial response to hormonal therapy.
Significance: Our study highlights a heterogenous genetic landscape and phenotypic pleiotropy in children with genetic IESS.
(© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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