Infantile Epileptic Spasms Syndrome Associated with a JARID2 Variant: A Case Diagnosed in Korea

Article information

Ann Child Neurol. 2026;34(3):247-250

Publication date (electronic) : 2026 July 1

doi : https://doi.org/10.26815/acn.2025.01298

Yoo Jung Lee, MD¹, Yoon Hee Jo, MD¹, Soo Young Rhu, MD², Ju Hyun Kong, MD², Yun-Jin Lee, MD, PhD², Sang Ook Nam, MD, PhD², Young Mi Kim, MD, PhD^,1

¹Department of Pediatrics, Pusan National University Hospital and Biomedical Research Institute, Pusan National University School of Medicine, Busan, Korea

²Department of Pediatrics, Pusan National University Children’s Hospital and Biomedical Research Institute, Pusan National University School of Medicine, Yangsan, Korea

Corresponding author: Young Mi Kim, MD, PhD Department of Pediatrics, Pusan National University Hospital and Biomedical Research Institute, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea Tel: +82-51-240-7298 Fax: +82-51-248-6205 E-mail: pink2129@naver.com

Received 2025 December 12; Revised 2026 April 17; Accepted 2026 April 24.

Infantile epileptic spasms syndrome (IESS) is a severe developmental and epileptic encephalopathy of infancy characterized by epileptic spasms, hypsarrhythmia, and developmental stagnation or regression [1]. Its estimated incidence is 1 in 2,000–6,000 live births, and most cases occur between 3 and 12 months of age [2]. IESS has diverse etiologies; however, approximately 40% to 50% of cases remain cryptogenic or idiopathic [3]. First-line treatments include adrenocorticotropic hormone, high-dose corticosteroids, and vigabatrin, which are particularly effective in patients with tuberous sclerosis [4]. Nevertheless, even when treatment is initiated early, many patients continue to experience persistent seizures or developmental impairment [5].

The Jumonji AT-rich interactive domain 2 (JARID2) gene encodes a regulatory protein that serves as an essential component of polycomb repressive complex 2 (PRC2), which regulates chromatin structure and gene expression through histone H3 lysine 27 site (H3K27) trimethylation [6]. This protein plays key roles in neurogenesis, neuronal migration, and synaptogenesis. JARID2 dysfunction has been associated with neurodevelopmental disorders characterized by developmental delay, intellectual disability, and distinctive facial features [7-9]. JARID2-associated neurodevelopmental disorder (OMIM #620098) has recently been recognized as a distinct condition caused by pathogenic JARID2 variants [9]. Although seizures have been reported in some affected patients, infantile spasms associated with JARID2 variants have rarely been described and remain poorly characterized [7-9].

Here, we report a case of IESS associated with a JARID2 variant in a patient diagnosed in Korea. This case expands the clinical spectrum of JARID2-associated disorders and highlights the importance of early genetic diagnosis.

The proband was a girl born at 34 weeks and 3 days of gestation via vaginal delivery, with a birth weight of 2,430 g. She required brief ventilatory support for transient tachypnea of the newborn but recovered without complications. No significant perinatal insults were identified. Her mother was Vietnamese, and her father was Korean; both the father and the paternal aunt had mild developmental delay. At her first outpatient visit, the patient’s corrected age was 5 months. At that time, she presented with clusters of sudden, startle-like flexion movements involving the limbs and trunk while awake. These episodes occurred several times daily and lasted less than 2 seconds. Developmentally, she had poor head control and lacked social smiling and eye contact, suggesting developmental stagnation. Examination revealed intermittent exotropia, mild facial dysmorphism with ptosis, axial muscle weakness, poor visual tracking, and decreased voluntary movements, without asymmetry or focal neurological deficits. The Korean Developmental Screening Test, performed at the initial evaluation at a corrected age of 5 months, showed global developmental delay across multiple domains.

Initial electroencephalography (EEG) showed classic hypsarrhythmia (Fig. 1A). Combination therapy with vigabatrin (100 mg/kg/day) and high-dose prednisolone (10 mg four times daily) was initiated. The spasms resolved completely within 10 days. Two weeks later, follow-up EEG still showed hypsarrhythmia, although the spike frequency was reduced and electrodecremental events were shorter. One month later, EEG demonstrated diffuse delta slowing with focal interictal epileptiform discharges in the right central (C4) and left parietal (P3) regions. Subsequent EEGs showed progressive improvement: hypsarrhythmia had disappeared by 8 months of age, and normal sleep architecture and background rhythms had been restored without epileptiform discharges by 2 years of age.

Fig. 1.

(A) Initial sleep electroencephalography. (B) Brain magnetic resonance imaging obtained at 2 years of age, showing increased periventricular T2/fluid-attenuated inversion recovery signal intensity and mild white matter volume loss.

Brain magnetic resonance imaging (MRI) at 7 months showed nearly normal myelination. At 2 years, follow-up MRI demonstrated increased T2/fluid-attenuated inversion recovery signal intensity and mild periventricular white matter volume loss, findings suggestive of periventricular leukomalacia (Fig. 1B).

All metabolic and biochemical test results, including tandem mass spectrometry, thyroid function testing, serum lactate/pyruvate, amino acids, ammonia, creatine kinase, urine glycosaminoglycans, and organic acids, were within normal limits. Peripheral blood karyotyping and chromosomal microarray analysis were unremarkable.

Whole-exome sequencing performed using SureSelect Human All Exon V6 (Agilent, Santa Clara, CA, USA) and NovaSeq (Illumina, San Diego, CA, USA) identified a heterozygous JARID2 variant, NM_004973.4:c.1945+1G>A (Fig. 2A). This variant affects the canonical splice donor site and was reported as likely pathogenic in the clinical diagnostic laboratory report. As a canonical splice-site variant, it is predicted to disrupt normal RNA splicing. However, its pathogenicity should be interpreted cautiously due to the observed paternal inheritance pattern, which was confirmed by Sanger sequencing (Fig. 2B).

Fig. 2.

(A) Whole-exome sequencing identifying the heterozygous Jumonji AT-rich interactive domain 2 (JARID2) splice-site variant (NM_004973.4:c.1945+1G>A). (B) Pedigree demonstrating paternal inheritance of the variant. IESS, infantile epileptic spasms syndrome.

The patient remained seizure-free after 2 months of treatment. Prednisolone was tapered over 8 weeks, and vigabatrin was discontinued by 2 years of age. During the subsequent 4 years of follow-up, no seizure recurrence was observed. At her most recent evaluation (age 6 years and 8 months), she had intellectual disability and spastic diplegia requiring rehabilitation therapy.

JARID2 encodes a DNA-binding transcriptional repressor that recruits PRC2 to genomic targets, thereby regulating chromatin accessibility and gene silencing [6]. This function is essential for brain development, particularly neurogenesis, neuronal migration, and synaptic maturation [6,8]. Pathogenic variants, including truncating and splice-site variants, may lead to loss of PRC2-mediated histone modification and dysregulation of neuronal gene expression [6]. Clinically, JARID2-related neurodevelopmental disorders are characterized by global developmental delay, hypotonia, intellectual disability, autism, and facial features such as ptosis, hypertelorism, and a broad nasal bridge [8,9]. Seizures have been described in some patients, most commonly as focal or generalized seizures; however, infantile spasms associated with JARID2 variants have rarely been reported and remain poorly characterized [7-9]. A previous report described a patient with a de novo JARID2 variant who presented with infantile spasms that evolved into Lennox–Gastaut syndrome, although that variant was classified as a variant of uncertain significance [10]. Accordingly, our case further broadens the clinical spectrum of JARID2-associated neurodevelopmental disorders, particularly with respect to IESS. This patient showed the classic triad of epileptic spasms, hypsarrhythmia, and developmental stagnation, fulfilling the diagnostic criteria for IESS [1,2]. Notably, she achieved complete seizure remission and EEG normalization within several months of receiving combined therapy with vigabatrin and corticosteroids. Such improvement is uncommon in genetic epileptic encephalopathies, which are often treatment-resistant and associated with poor developmental outcomes [1,2]. This clinical course suggests that early treatment during a critical neurodevelopmental period may have contributed to the favorable seizure and EEG outcomes observed in this patient, consistent with the known effectiveness of standard therapy for IESS.

Another distinctive feature of this case was the paternal inheritance of the likely pathogenic variant, in contrast to the predominantly de novo occurrence reported in previous studies [7-9]. The observation that the father and paternal aunt had only mild developmental delay without epilepsy may indicate phenotypic variability; however, this interpretation is limited by the absence of genetic confirmation in the paternal aunt and the small number of affected family members. Additional genetic or environmental modifiers may also have contributed to the observed intrafamilial variability. Although the variant was classified as likely pathogenic in the clinical diagnostic setting, its pathogenicity should be interpreted cautiously in the context of confirmed paternal inheritance, and the genotype–phenotype association in this family remains to be clarified. Further genetic evaluation of family members would therefore be necessary to better define the genotype–phenotype relationship.

Pathophysiologically, the JARID2–PRC2 complex regulates neuronal gene networks involved in synaptic signaling and the formation of cortical connectivity [6,7]. Disruption of this pathway during early brain development may alter the balance between excitatory and inhibitory neurotransmission, potentially leading to the corticothalamic hyperexcitability characteristic of infantile spasms [2,5]. Furthermore, the seizure resolution and EEG normalization observed in this patient suggest that these early neural network abnormalities may undergo partial functional compensation over time.

In conclusion, we report a family in Korea with a JARID2 variant and, to our knowledge, the first case demonstrating an association with IESS. This report expands the phenotypic spectrum of JARID2-related disorders and underscores the importance of comprehensive genetic evaluation in patients with unexplained infantile spasms and developmental delay. Further research is needed to clarify the range of phenotypes and the pathogenic mechanisms associated with JARID2 variants. Early identification of the underlying genetic etiology may also improve prognostic assessment, inform family counseling, and enhance understanding of the links between chromatin regulatory mechanisms and epileptic encephalopathies.

Informed consent was obtained from the patient’s parents. Patient medical records and other data were anonymized to protect confidentiality.