Yield of modern genetic evaluation for patients with proximal hypospadias and descended gonads.


Divison of Pediatric Urology, Connecticut Children's Hospital, Hartford, CT 06106, USA. Electronic address: [Email]


BACKGROUND : Although the pediatric urologic community has embraced a multidisciplinary genetic and endocrine evaluation for newborns with ambiguous genitalia, this approach has been reserved for the most severe cases of undervirilized 46,XY individuals despite growing evidence that genetic differences are found even in patients whose only genitourinary anomaly appears to be proximal hypospadias. Identifying these genetic differences is vital for counseling patients as they move through puberty to parenthood as well as parents on future pregnancies.
OBJECTIVE : The primary objective was to evaluate genetic diagnosis in patients with proximal hypospadias. The authors hypothesized the more sensitive genetic evaluation available in the modern era will reveal a high rate of patients with proximal hypospadias and descended testicles who are found to have a genetic difference, supporting a thorough genetic evaluation in these patients.
METHODS : A retrospective review was performed of all patients who underwent surgical correction for proximal hypospadias at a single institution from January 1, 2010, to December 31, 2016. Those with midshaft hypospadias were excluded as were patients whose primary surgery was performed at an outside institution. Patient characteristics, including demographics, clinical presentation, genetic evaluation, and referral to a multidisciplinary difference of sex development (DSD) clinic, were collected. The chi-squared test and t-test were used for analysis.
RESULTS : There were 112 patients with proximal hypospadias who met the inclusion criteria. Of these, 91 had bilaterally descended testicles, whereas 21 had one or more undescended testicles. Thirty-three percent of patients with isolated proximal hypospadias received genetic testing of some kind, with 24% seen in the multidisciplinary DSD clinic. Four patients had an associated genetic syndrome identified, and 5 had a genetic difference of unknown clinical significance. Overall, 10% of patients with proximal hypospadias and descended testicles had an identifiable genetic difference vs 33% with associated cryptorchidism. Of these, one patient with proximal hypospadias and descended testicles had a genetic difference of known clinical significance that was likely to have been missed in the absence of an evaluation by a geneticist.
CONCLUSIONS : There was a high rate of identifiable genetic differences in patients whose only genitourinary abnormality was proximal hypospadias, especially with the 1% risk of a likely missed diagnosis. These findings support the discussion of a genetic evaluation for all patients with proximal hypospadias, regardless of the testicular location.


Cryptorchidism,Differences in sex development,Genetics,Hypospadias,Proximal hypospadias,

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