Inherited <i>RORB</i> pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Sadleir, Lynette G.; Valles-Ibáñez, Guillem de; King, Chontelle; Coleman, Matthew; Mossman, Stuart; Paterson, Sarah; Nguyen, John; Berkovic, Samuel F.; Mullen, Saul A.; Bahlo, Melanie; Hildebrand, Michael S.; Mefford, Heather C; Scheffer, Ingrid E.

doi:10.1111/epi.16475

Cited by 17 publications

(14 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other sporadic cases were also reported by these authors with different alteration on RORB , including two more cases with absences, EM and GTCS ( Table 3 ). Sadleir et al (2020) identified four novel RORB variants in 11 affected patients from four families with different epileptic syndromes [ 50 ]. Of this series, one case was diagnosed with EMA and occipital lobe epilepsy, presenting also GTCS.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, another patient from a different family also presented absences with EM and GTCS, but was diagnosed with juvenile absence epilepsy and idiopathic photosensitive occipital lobe epilepsy ( Table 3 ). Although the predominant epileptic phenotype of this cohort was represented by the overlap of photosensitive generalized and occipital epilepsy, the authors underlined the important role of occipital cortex in starting epileptic discharge in idiopathic generalized epilepsies such as EMA [ 50 ]. Finally, Morea et al (2021) described another case with a RORB variant diagnosed with EMA [ 11 ]…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Mayo

Gómez-Manjón

Fernández-Martínez

et al. 2021

IJMS

View full text Add to dashboard Cite

Eyelid myoclonia with absences (EMA), also known as Jeavons syndrome (JS) is a childhood onset epileptic syndrome with manifestations involving a clinical triad of absence seizures with eyelid myoclonia (EM), photosensitivity (PS), and seizures or electroencephalogram (EEG) paroxysms induced by eye closure. Although a genetic contribution to this syndrome is likely and some genetic alterations have been defined in several cases, the genes responsible for have not been identified. In this review, patients diagnosed with EMA (or EMA-like phenotype) with a genetic diagnosis are summarized. Based on this, four genes could be associated to this syndrome (SYNGAP1, KIA02022/NEXMIF, RORB, and CHD2). Moreover, although there is not enough evidence yet to consider them as candidate for EMA, three more genes present also different alterations in some patients with clinical diagnosis of the disease (SLC2A1, NAA10, and KCNB1). Therefore, a possible relationship of these genes with the disease is discussed in this review.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Mayo

Gómez-Manjón

Fernández-Martínez

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Recently, variants in the gene RORB were identified in individuals and families manifesting both photosensitive generalized seizures and focal (occipital) seizures. 17 Future studies should continue to explore the genetic architecture of the combined epilepsies.…”

Section: F I G U R Ementioning

confidence: 99%

Generalized, focal, and combined epilepsies in families: New evidence for distinct genetic factors

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objective: To determine the roles of shared and distinct genetic influences on generalized and focal epilepsy operating in individuals who manifest features of both types (combined epilepsies), and in families manifesting both generalized and focal epilepsies in separate individuals (mixed families). Methods: We analyzed the deeply phenotyped Epi4K cohort of multiplex families (≥3 affected individuals per family) using methods that quantify the aggregation of phenotypes within families and the relatedness of individuals with different phenotypes within family pedigrees. Results: The cohort included 281 families containing 1021 individuals with generalized (n = 484), focal (304), combined (51), or unclassified (182) epilepsies. The odds of combined epilepsy was higher in relatives of participants with combined epilepsy than in relatives of those with other epilepsy types (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.7-16.1, P = .004). Individuals with combined epilepsy co-occurred in families more often than expected by chance (P = .03). Within mixed families, individuals with each type of epilepsy were more closely related to relatives with the same type than to relatives with other types (P < .001). Significance: These findings suggest that distinct genetic influences underlie the recently recognized entity of combined epilepsies, just as generalized epilepsies and focal epilepsies each have distinct genetic influences. Mixed families may in part reflect chance co-occurrence of these distinct genetic influences. These conclusions have important implications for molecular genetic studies aimed at identifying genetic determinants of the epilepsies.

show abstract

“…Indeed, the two brothers were affected by mild NDDs: the first one had an expressive language impairment, whereas the second one displays an unusual form of ASD, characterized by very intense visual sensory self-stimulation and stereotypic behaviors. A recent report [ 3 ] identified novel inherited heterozygous RORB variants in fourteen individuals belonging to four families: eleven of them were affected by epilepsy, one had intellectual disability, and two were unaffected. Epilepsy was focal or generalized in five patients, whereas six patients had both types.…”

Section: Resultsmentioning

confidence: 99%

“…In summary, it appears that RORB variants are mainly associated with different forms of epilepsy (including eyelid myoclonia with absence epilepsy, generalized epilepsy, and occipital epilepsy), often in comorbidity with neurodevelopmental disorders such as intellectual disability, ADHD, and ASD. However, sporadic cases of RORB variants have also been described in association with severe forms of ID only [ 3 ] and ASD [ 4 ].…”

Section: Resultsmentioning

confidence: 99%

Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results

Lintas

Sacco

Azzarà

et al. 2021

JCM

View full text Add to dashboard Cite

ASD genetic diagnosis has dramatically improved due to NGS technologies, and many new causative genes have been discovered. Consequently, new ASD phenotypes have emerged. An extensive exome sequencing study carried out by the Autism Sequencing Consortium (ASC) was published in February 2020. The study identified 102 genes which are de novo mutated in subjects affected by autism spectrum disorder (ASD) or similar neurodevelopmental disorders (NDDs). The majority of these genes was already known to be implicated in ASD or NDDs, whereas approximately 30 genes were considered “novel” as either they were not previously associated with ASD/NDDs or very little information about them was present in the literature. The aim of this work is to review the current literature since the publication of the ASC paper to see if new data mainly concerning genotype–phenotype correlations of the novel genes have been added to the existing one. We found new important clinical and molecular data for 6 of the 30 novel genes. Though the broad and overlapping neurodevelopmental phenotypes observed in most monogenic forms of NDDs make it difficult for the clinical geneticist to address gene-specific tests, knowledge of these new data can at least help to prioritize and interpret results of pangenomic tests to some extent. Indeed, for some of the new emerging genes analyzed in the present work, specific clinical features emerged that may help the clinical geneticist to make the final diagnosis by associating the genetic test results with the phenotype. The importance of this relatively new approach known as “reverse phenotyping” will be discussed.

show abstract

Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Cited by 17 publications

References 18 publications

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature

Generalized, focal, and combined epilepsies in families: New evidence for distinct genetic factors

Genotype–Phenotype Correlations in Relation to Newly Emerging Monogenic Forms of Autism Spectrum Disorder and Associated Neurodevelopmental Disorders: The Importance of Phenotype Reevaluation after Pangenomic Results

Contact Info

Product

Resources

About