A novel RORA genetic variant associated with early-onset obesity and insomnia

Retinoic acid-related orphan receptor alpha (RORA) pathogenic variants cause intellectual developmental disorder with or without epilepsy or cerebellar ataxia (IDDECA). Herein, we present a female patient with a novel heterozygous likely pathogenic RORA variant, c.484C > T p.(Arg162∗), with a clinical manifestation overlapping IDDECA. The patient also presented previously undocumented symptoms, namely, early-onset obesity and insomnia. Furthermore, parental testing revealed inheritance from the mother who presented a congruent phenotype. This suggests a role for RORA in both sleep and metabolism whilst extending the phenotypic spectrum of IDDECA. Notwithstanding, more fundamental work is needed to delineate the role of RORA variants in disease.