Professionals

The syndrome resulting from mutation in ARHGEF9 can include Developmental Delay (DD), Intellectual Disability (ID), seizures or epilepsy and abnormal baseline EEG, sleep abnormalities, as well as varying presentation of behavioral features that resemble autism, anxiety, and hyperactivity. Because the gene is X-linked, there is varying presentation in females depending upon skewing in favor of the abnormal X-chromosome common among the female patients that display symptoms. The mutant allele can be inherited from an asymptomatic mother who is a heterozygous carrier, although the inheritance is typically de novo. There is a wide range of different mutations that have been identified (>30) including micro, partial, and full deletions, missense and nonsense mutations, balanced translocations, paracentric inversions, and splice variants. Although a rare syndrome (~60 patients as of 2024), the growing number of reports suggests that ARHGEF9 mutation may be among the more common forms of X-linked ID.