A Rare Case of Hao-Fountain Syndrome Mimicking Fragile X Syndrome

Abstract

Hao-Fountain syndrome (HAFOUS) is a rare neurodevelopmental disorder caused by mutations in the ubiquitin-specific protease 7 (USP7) gene for endosomal recycling. The diagnosis is often challenging due to the nonspecific presentation of intellectual disability and developmental delay, often accompanied by dysmorphic facies. In this case, we present an 18-year-old female with intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and dysmorphic facies who had undergone single nucleotide polymorphism (SNP) microarray and fragile X polymerase chain reaction (PCR) testing five years prior to diagnosis, both returning with negative results for genetic anomalies. The patient was managed symptomatically for ADHD until recently when the topic of a possible genetic condition was reintroduced to the family, who were agreeable to a referral to a medical geneticist and repeat genetic testing. Repeat testing, but now with whole-exome sequence (WES) analysis, revealed a pathogenic variant of the USP7 gene, prompting the diagnosis of Hao-Fountain syndrome. Our patient continues to be symptomatically managed for ADHD and intellectual disability. Educational resources and support group information were also shared and discussed with the patient and her family in the wake of this rare diagnosis.