To date, described individuals with pathogenic RFX3variants have demonstrated global developmental delay in childhood, and as older children or young adults, some degree of intellectual disability (ID), ranging from borderline to moderate ID.
The majority (72%) have a formal diagnosis of autism, but almost all are noted to have “autistic features” such as repetitive behaviours or hypersensitivities to sound. About half are diagnosed with attention-deficit/hyperactivity disorder (ADHD). Most reported cases also have behavioral difficulties as a component of the phenotype, including easy excitability, hypersensitivity to sensory stimuli, anxiety, emotional dysregulation and aggression. Sleep challenges were reported in just under half of individuals (limited duration, overnight awakenings, or early morning awakenings).
Dysmorphisms were subtle and nonspecific if present (broad nasal bridge, arched palate, tapered fingers, widely spaced toes). Both macrocephaly and microcephaly were observed.
MRI findings were not uniformly available, but results were typically normal or nonspecific (uncal asymmetry, white matter changes, prominent ventricles, partially empty sella, thinning of corpus callosum). Seizures occurred in only 4 of the 18 individuals and were varying in semiology (absence, focal, generalized). In individuals past pubertal age, there was often note of cognitive or behavioural regression (increased aggression), with several exhibiting psychotic symptoms (hallucinations, conversations with imaginary friends). Thus far, there are more males identified compared to females but no definite sex-based differences in phenotype severity.
RFX3