P330: Understanding the disease mechanisms and copy number variations at 17p11.2 locus that do not encompass the dosage sensitive RAI1 gene

workforce may overwhelm existing clinical capacity.Here, we describe the changing clinical workflows and diagnostic outcomes for patients evaluated for hypermobility at a private genomics clinic.Methods: In 2021, the clinic instituted a split care model where clinical staff review all referrals and offer either a traditional medical geneticist (MD) or a genetic counselor-only (GC) clinic appointment based on whether a geneticist's physical exam is necessary to determine testing plan or diagnosis.From October 2021 to April 2023, adult patients referred for hypermobility were scheduled for MD clinics for evaluation for hEDS/HSD based on clinical criteria.From April 2023 to April 2024, patients were provided with an option for evaluation in an MD clinic or a GC-only clinic, which would only include ordering genetic testing for CTDs and not a physical exam.Patients who reported a personal or family history suspicious for genetic CTD such as aortic aneurysm, retinal detachment, and other designated features were scheduled for MD clinics.As of April 2024, patients referred for hypermobility in the absence of other suspicious features are only offered GC appointments.We performed a retrospective chart review to assess the diagnostic outcomes for adult patients referred for evaluation of hypermobility/EDS during this time period.Pediatric patients and those with concerning features for other genetic CTDs were excluded from this analysis.Patient demographic details, clinical exam features, and genetic testing results were tabulated.Results: A total of 115 adult patients were referred for hypermobility/EDS during the evaluation period.Most patients were female (94.8%), and median age was 30 years old (range 18-79).Seventy-seven patients underwent MD evaluations, and 7 (9.1%)met strict diagnostic criteria for hEDS.Other clinical diagnoses in this cohort included 58 (75.3%) with HSD (generalized or localized HSD) and 2 with asymptomatic generalized joint hypermobility.Of the 74 patients for whom an hEDS diagnostic checklist was completed during their clinic visit, 62 (83.8%) had generalized hypermobility by Beighton scale (average score 6.4, range 0-9).The most common Criteria 2 features included piezogenic papules (74.3%), soft/velvety skin (70.3%), and dental crowding and high/narrow palate (33.8%).Rare features observed in less than 10% of our cohort included mitral valve prolapse, arachnodactyly, atrophic scarring, organ prolapse, increased arm span to height, multiple abdominal hernias, and aortic root dilatation.Genetic testing was ordered for 26 MD patients, and one was identified to have a pathogenic variant in FBN1; this patient's physical exam was clinically diagnostic for Marfan syndrome at the time testing was ordered, and they reported a known family history of Marfan syndrome.Remaining genetic testing results were negative/non-diagnostic. Thirty-eight patients were seen for GC visits during the study period.Thirty-five elected to undergo genetic testing, and 34 were negative/non-diagnostic.One patient was identified to have a pathogenic variant in FBN1.The patient's reported history at the time testing was ordered raised suspicion for Marfan syndrome, including mitral valve prolapse, aortic dilatation (Z-score 2.53), and dural ectasia.Conclusion: We described detailed clinical and genetic diagnostic findings for a cohort of patients referred for evaluation of hypermobility.These findings highlight the potential utility of a GC-only clinic to address high referral volumes with minimal risk, as a vast majority of patients do not have an identifiable genetic CTD.