Aug 2026· International Journal of Molecular Sciences· 0 citations· 22 references
TL;DR
This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption, and highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.
Abstract
Regulatory Factor X3 (RFX3—OMIM#601337) encodes a transcription factor that is highly expressed in the human brain, particularly during neurodevelopment. It has been previously associated with neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual developmental disorder, and attention-deficit/hyperactivity disorder. However, the neurological and epileptic features remain poorly characterized, and no phenotype has yet been formally annotated in OMIM. Here, we report the second known case of Infantile Epileptic Spasms Syndrome (IESS) associated with RFX3 variants. The patient developed clusters of extensor spasms associated with eye deviation and achieved complete remission within two weeks following vigabatrin and ACTH therapy, remaining seizure-free thereafter. During follow-up, he presented with global developmental delay, ASD, and facial dysmorphisms. Genetic analysis by array comparative genomic hybridization identified a de novo heterozygous microdeletion of approximately 147 kb at 9p24.2, involving the initial exons of RFX3 (NM_134428). This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption. It highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders.
This study may expand the mutation and phenotypic spectrum of SETD1A-related disorders, establishing the relationship between SETD1A variants and isolated early-onset epilepsy without accompanying severe neurodevelopmental deficits, and highlighting the value of genetic testing in infants with unexplained epilepsy.
Rina Su, Lei Zhu, Lin Jiang et al.· Frontiers in Neuroscience· 0 citations
A case series of an additional 13 affected individuals with RNF13 variants (2 missense, 11 truncating) supports and broadens previous reports and helps to define a narrow but critical region of the protein that is intolerant to truncating variation, although the gene is not highly constrained.
D. Latner, S. Hiatt, C. Finnila et al.· American Journal of Medical...· 0 citations
The findings support the pathogenicity of this variant and further expand the pathogenic variant spectrum of the PPP2CA gene, and the observed genotype–phenotype correlation provides valuable information for prognosis and genetic counseling.
Lei Xu, Yanfeng Shen, Guixiang Zhang· Frontiers in Psychiatry· 0 citations
The findings expand the genotypic and phenotypic spectrum of DEE96, demonstrating that DEE96 manifests as a multisystem disorder with prenatal onset, and supports considering NSF variants in the differential diagnosis of complex fetal syndromes with neurological and hematological abnormalities.
Qi Yang, Zailong Qin, Jiao Li et al.· Frontiers in Genetics· 0 citations
The identification of both novel and previously reported pathogenic variants expands the mutational spectrum of PURA and underscores the importance of integrating clinical, molecular, and bioinformatic data for accurate variant interpretation.
A. Madej-Pilarczyk, Marzena Gawlik, Beata Chałupczyńska et al.· Genes· 0 citations
Abstract Objective Neurodevelopmental disorders (NDDs) and epilepsy are often associated. Increasing evidence highlights a pivotal role for pathogenic variants in genes encoding synaptic scaffolding proteins. Within this group, TANC2 has recently been implicated in intellectual developmental disorder with autistic features and language delay, with or without seizures; however, its full clinical spectrum and contribution to specific epileptic encephalopathies remain incompletely defined. Methods We describe the electroclinical and developmental features of three patients carrying truncating TANC2 variants identified through trio‐exome sequencing within the European collaborative platform NETRE. Clinical, neuropsychological, and EEG data were collected and compared with prior reports. Results Case #1 met Lennox–Gastaut syndrome (LGS) criteria, showing early drug resistance followed by partial cognitive recovery and sustained seizure control on felbamate monotherapy. Case #2 presented with ASD and multiple seizure types—including focal, atypical absence, and tonic—finally reaching prolonged remission and borderline intellectual functioning. Case #3 showed early‐onset, drug‐resistant polymorphic seizures with persistent bifrontal epileptiform discharges and severe developmental impairment, consistent with an LGS‐like phenotype, with seizure freedom achieved under a limited polytherapy regimen. Significance Our findings expand the electroclinical spectrum of TANC2‐related disorders, supporting a continuum ranging from NDD‐associated epilepsy to DEE, including LGS in selected patients. Plain Language Summary TANC2 is a gene involved in brain development and synaptic function. Changes in this gene have been linked to neurodevelopmental disorders, autism, intellectual disability, and epilepsy. We describe three individuals with previously unreported truncating TANC2 variants and different epilepsy phenotypes, including one patient fulfilling criteria for Lennox–Gastaut syndrome (LGS) and another with LGS‐like features. Although seizures were initially difficult to treat in some cases, seizure control was eventually achieved. These findings expand the known clinical spectrum of TANC2‐related disorders and suggest that selected patients may have a more favorable seizure course than expected.
L. Perilli, Carlotta Stipa, Gianmichele Villano et al.· Epilepsia Open· 0 citations