2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-VUS in<em> RHOBTB2</em> Gene Detected on Rapid Whole Genome Sequencing in a Patient with Worsening Seizures and Developmental Regression

VUS in RHOBTB2 Gene Detected on Rapid Whole Genome Sequencing in a Patient with Worsening Seizures and Developmental Regression

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The article discusses a case study of a 9-month-old female who presented with worsening seizures and regression of developmental milestones. The patient had a complex medical history, including prematurity, prenatal drug exposure, and suspected infection. The seizures initially resembled breath holding spells with nystagmus but evolved over time to tonic-clonic seizures. The seizures were resistant to pharmacotherapy. The patient also had optic nerve hypoplasia and mild diffuse cerebral volume loss on brain imaging.<br /><br />Genetic testing was performed, and a heterozygous autosomal dominant variant, c.717G>T, p.W239C, in the RHOBTB2 gene was detected. This variant is classified as a variant of uncertain significance, as it has not been previously reported in genetic databases or literature. In silico models predicted the variant to have a deleterious effect.<br /><br />The RHOBTB2 gene is known to be associated with developmental and epileptic encephalopathy, as well as encephalopathy with paroxysmal movement disorders. This case adds to the phenotypic spectrum of RHOBTB2 gene-associated epilepsy.<br /><br />The article highlights the value of rapid whole exome sequencing in diagnosing patients outside of the ICU setting. Additional studies have also reported variants in the RHOBTB2 gene causing epileptic encephalopathy.<br /><br />In conclusion, the case study identifies a novel variant in the RHOBTB2 gene in a patient with worsening seizures and developmental regression. This adds to the understanding of the phenotypic spectrum associated with RHOBTB2 gene-associated epilepsy. The study highlights the importance of genetic testing and rapid whole exome sequencing for timely diagnosis.

Asset Subtitle

Presenting Author - Monika Williams, MD; Co-Author - Steven P. Trau, MD; Co-Author - Elizabeth R. Jalazo, MD;

Meta Tag

Brain/Nervous System

Clinical History

Cognitive Disorders

Genome sequencing

Sequencing

Variant Detection

Co-Author Steven P. Trau, MD

Co-Author Elizabeth R. Jalazo, MD

Presenting Author Monika Williams, MD

Keywords

seizures

developmental milestones

prematurity

genetic testing

RHOBTB2 gene

variant of uncertain significance

deleterious effect

phenotypic spectrum

rapid whole exome sequencing

epileptic encephalopathy