Clinical utility of early rapid genome sequencing in the evaluation of patients with differences of sex development

Apoorva Aekka*, Allison Goetsch Weisman, Jaclyn Papadakis, Elizabeth Yerkes, Joshua Baker, Mahima Keswani, Joanna Weinstein, Courtney Finlayson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Establishing an early and accurate genetic diagnosis among patients with differences of sex development (DSD) is crucial in guiding the complex medical and psychosocial care they require. Genetic testing routinely utilized in clinical practice for this population is predicated upon physical exam findings and biochemical and endocrine profiling. This approach, however, is inefficient and unstandardized. Many patients with DSD, particularly those with 46,XY DSD, never receive a molecular genetic diagnosis. Rapid genome sequencing (rGS) is gaining momentum as a first-tier diagnostic instrument in the evaluation of patients with DSD given its ability to provide greater diagnostic yield and timely results. We present the case of a patient with nonbinary genitalia and systemic findings for whom rGS identified a novel variant of the WT1 gene and resulted in a molecular diagnosis within two weeks of life. This timeframe of diagnosis for syndromic DSD is largely unprecedented at our institution. Rapid GS expedited mobilization of a multidisciplinary medical team; enabled early understanding of clinical trajectory; informed planning of medical and surgical interventions; and guided individualized psychosocial support provided to the family. This case highlights the potential of early rGS in transforming the evaluation and care of patients with DSD.

Original languageEnglish (US)
Pages (from-to)351-357
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume194
Issue number2
DOIs
StatePublished - Feb 2024

Keywords

  • DSD
  • WT1-related disorder
  • genomic sequencing
  • molecular diagnostics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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