ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2022) 19 6.10 | DOI: 10.1530/ey.19.6.10


J Clin Endocrinol Metab. 2022 Apr 19;107(5):e1797-e1806. PMID: 35134971, doi: 10.1210/clinem/dgac064.

Brief Summary: This retrospective clinical research reports the clinical/biochemical, radiological, and genetic findings of a large cohort of 209 non-syndromic 46,XY DSD patients from a single tertiary center collected over the last 25 years in Brazil. A molecular diagnosis was achieved in 59.3% of patients.

The authors classified this cohort into 3 groups based on clinical, hormonal, imaging assessment, and histologic findings of the patients; i) gonadal dysgenesis, ii) disorders of androgen and anti-Mullerian hormone (AMH) secretion or action, and iii) DSD of unknown etiology. For the etiologic diagnosis, the patients were sequenced by Sanger, and/or massively parallel sequencing (MPS) technologies including DSD Target panel or whole-exome sequencing (WES).

Overall, a molecular diagnosis was achieved in 59.3% of the cohort. Pathogenic NR5A1 variants were the most common genetic findings among patients initially classified as DSD of clinically unknown etiology, emphasizing its broad phenotype presentation. Deleterious DHX37 variants were the most common genetic findings in patients with gonadal dysgenesis, especially in those with testicular regression syndrome.

The revised DSD diagnostic algorithm (1) still recommends clinical/biochemical and imaging testing as the initial approach for all individuals with a suspected DSD. Nevertheless, because of the overlapping clinical/biochemical phenotypes, the authors recommend that MPS should be incorporated as a first-line approach because it potentially decreases the complexity of the diagnostic workup, would minimize patient handling, improve diagnosis accuracy, and probably decrease the costs.

References: 1. Cools M, Nordenström A, Robeva R, Hall J, Westerveld P, Flück C, Köhler B, Berra M, Springer A, Schweizer K, Pasterski V; COST Action BM1303 working group 1. Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nat Rev Endocrinol. 2018 Jul;14(7):415–429. doi: 10.1038/s41574-018-0010-8. PMID: 29769693; PMCID: PMC7136158.

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