Skip to main content

Conference Program

Subpage Hero

Loading

Clinical Utility and Diagnostic Yield of Comprehensive Genetic Testing in Adults with Intellectual and Developmental Disabilities: A Single-Center Experience 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical-Adult
  • Secondary Categories:
    • Clinical-Adult & Pediatric
Introduction:
Introduction: Genetic testing is a standard practice for children with intellectual and developmental disabilities (IDD), yet adults with IDD often lack comprehensive genetic evaluations, despite the potential for significant diagnostic and clinical benefits. The American College of Medical Genetics and Genomics (ACMG) recommends exome and genome sequencing (ES/GS) as a first- or second-tier diagnostic tool for pediatric patients with IDD or congenital anomalies, citing higher diagnostic yields and cost-effectiveness when performed early in the diagnostic process. Extending comprehensive genetic testing to adults with IDD addresses a significant gap in healthcare, providing diagnostic clarity and therapeutic guidance for those who may not have been tested in childhood due to evolving technology or limited access. This study evaluates the diagnostic yield, introduces novel clinical utility metrics, and assesses the healthcare impact of genetic testing in adults with IDD. 

Methods:
Methods: A retrospective analysis was conducted on 69 adult IDD patients (ages 19-83, median 32) evaluated between January 2022 and October 2024. Testing strategies included chromosomal microarray, targeted panels, and comprehensive approaches such as whole exome sequencing (WES) and whole genome sequencing (WGS). 

Results:
Results: The overall diagnostic yield was 31.9% (22/69), with significant variation by testing strategy: 

  • WES/WGS: 36.8% (14/38) 

  • Sequential panels: 22.7% (7/31) 

  • Yield differential: 14.1% (95% CI: 8.3-19.9%, p<0.005) 


Specific diagnoses: 

Neurodevelopmental Disorders: 

  • FOXP1 (intellectual developmental disorder with language impairment) 

  • WDFY3 (neurodevelopmental disorder with autism) 

  • 16p11.2 duplication (neurodevelopmental disorder) 

  • 3q21.3q22.1 duplication (developmental delay syndrome) 

  • 8p23.1 deletion (developmental delay syndrome) 

  • RPS6KA3 (Coffin-Lowry syndrome) 

  • KMT2D (Kabuki syndrome) 

  • POGZ (White-Sutton syndrome) 

  • NIPBL (Cornelia de Lange Syndrome) 

  • Xq27.3-q28 Duplication Syndrome


Neurological Disorders: 


  • MECP2 (Rett syndrome) 

  • SRSF1 (developmental delay-seizure syndrome) 

  • GABRG2 (generalized epilepsy) 

  • PCDH19 (epilepsy and intellectual disability) 

  • CCM2 (cerebral cavernous malformation) 

  • PDYN (spinocerebellar ataxia 23) 

  • DYNC1H1 (malformations of cortical development) 


Multisystem Syndromes: 


  • ALMS1 (Alström syndrome) 

  • FBN1 (Marfan syndrome) 

  • 17q12 deletion (renal cysts and diabetes syndrome) 

  • Xp22.31 microdeletion (X-linked ichthyosis) 

  • 22q11.2 Deletion (DiGeorge Syndrome) 


Metabolic/Homeostasis Disorders: 


  • MT-TK (mitochondrial myopathy) 

  • CASR (calcium homeostasis disorder) 


Result categories and clinical impact:

1.Immediate Medical Management (28.9%): 

  • Direct therapeutic intervention (11.6%) 

  • Medication modification (17.4%) 

  • Acute surveillance initiation (13.0%)


2.Preventive Care Impact (34.8%): 


  • Disease-specific monitoring protocols (23.2%) 

  • Risk-reduction strategies (18.8%) 

  • Specialist referral networks (15.9%)


3.Long-term Care Planning (37.7%): 


  • Family cascade testing (26.1%) 

  • Reproductive counseling (18.8%) 

  • Resource coordination (14.5%)


Testing efficiency analysis: 

1. Definitive results: WES/WGS 86% vs. Sequential 64% 

2. Uncertain results requiring follow-up: 

- WES/WGS: 14% (5/38) 

  • Variant reclassification needed: 8% 

  • Familial testing needed: 5% 

  • Functional studies needed: 1% 


- Sequential: 36% (11/31) 


  • Additional panel testing needed: 18% 

  • Variant reclassification needed: 12% 

  • Familial testing needed: 6% 




Conclusion:
Conclusions: 

This analysis demonstrates the clinical value of comprehensive genetic testing in adults with intellectual and developmental disabilities (IDD), yielding a diagnostic rate comparable to pediatric populations and emphasizing the relevance of whole exome and whole genome sequencing (WES/WGS) in adult diagnostics. Our findings reinforce the ACMG’s guidelines for children and advocate extending these standards to adults with IDD to bridge an existing healthcare gap. Comprehensive testing strategies, particularly WES/WGS, showed the highest diagnostic efficiency, lower follow-up requirements, and broader clinical impact. These metrics provide an objective framework to assess and optimize diagnostic protocols, showing a measurable improvement in actionable findings and streamlined management for adults with IDD. 



Our study highlights the broad spectrum of genetic diagnoses in the adult IDD population and the tangible benefits, including timely medical interventions, preventive care, and long-term planning for patients and families. The results support the argument for genetic testing as a vital tool in adult care, reducing the diagnostic odyssey and associated costs. These findings suggest the need for guidelines inclusive of adults with IDD to ensure equitable access to genetic evaluations, optimizing patient care across the lifespan. 

Agenda

Sponsors