Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7

The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans. Reports from 15 individuals have described RFX-associated phenotype as a neurobehavioural disease, manifesting primarily with global developmental delay and intellectual disability. Autism spectrum disorder and attention deficit hyperactivity disorder have also been described in some children. Here we report a case of a 19-month-old with a de novo missense variant in RFX7 resulting in severe global developmental delay including significant speech delay, microcephaly, dyskinetic movements, and failure to thrive. This is the first association between variants in RFX7 and failure to thrive, expanding the phenotype of this newly described gene. In this report we will also show RFX7 associated progressive central nervous system involvement through serial brain imaging.