Diagnostic Approach to Fragile X Syndrome and Angelman Syndrome

Clinical Features and Diagnostic Testing

• The American Academy of Pediatrics recommends testing individuals with intellectual disability, global developmental delay, autism, or family history of the mutation for Fragile X syndrome 1
• If Fragile X testing is negative, consider Angelman syndrome testing by performing DNA methylation analysis using SNRPN or PW71B probes as the first-line test, which detects approximately 99% of Angelman syndrome cases 2, 1
• If only paternal methylation pattern is present, Angelman syndrome is confirmed, and if biparental inheritance is identified, Angelman syndrome is ruled out 3
• Approximately 70% of Angelman syndrome cases have a deletion of 15q11-q13 on the maternal chromosome 4
• Macroorchidism is a characteristic feature of Fragile X syndrome in post-pubertal males 5
• If Angelman syndrome testing is pursued and negative, consider that 15-20% of cases may be missed by standard methylation testing and may require UBE3A gene sequencing 5, 4