Is routine karyotyping necessary in the evaluation of hypospadias and cryptorchidism?

The incidence of intersex states has been reported to be 27% to 100% in patients with hypospadias and cryptorchidism, and routinely determining karyotypes has been recommended. This incidence seems much higher than in our experience. We reviewed the records of patients with hypospadias and/or chordee plus cryptorchidism as well as those referred with ambiguous genitalia to determine whether these findings were associated with a high incidence of chromosomal abnormalities and whether they warrant routine karyotype screening.

We reviewed the records of patients with undescended testis plus hypospadias and/or chordee, and those with ambiguous genitalia who presented between 1986 and 1999. Patients without karyotype determination, and those with iatrogenic cryptorchidism, retractile testes, congenital adrenal hyperplasia or female-appearing external genitalia were excluded from study. Meatus and testis locations at surgery, and associated Müllerian structures and medical conditions were documented. Fisher's exact test was done to determine statistical significance.

Of the 113 patients whose records matched study inclusion criteria only 48 had complete anatomical, karyotypic, pathological and radiographic information available. Eight patients (16.7%) had chromosomal abnormalities, including 2 (4.2%) with karyotypic intersex disorder and 6 (12.5%) with autosomal chromosomal abnormalities. There were persistent Müllerian structures in 2 patients (4.2%) with a normal 46 XY karyotype. As described by a staff pediatric urologist, 20 patients (41.7%) had ambiguous genitalia and 8 of the 48 (16.7%) had nonpalpable cryptorchidism. Ambiguous genitalia were associated with chromosomal abnormalities, in 4 of the 20 cases, including 2 karyotypic intersex cases. Only 3 patients with ambiguous genitalia had nonpalpable gonads and 1 with karyotypic intersex disorder had a nonpalpable gonad that involved the testicular elements only. The incidence of autosomal chromosomal abnormalities was not significant (2-tailed Fisher's exact test p <==0.05) and the incidence of karyotypic (autosomal or sex) abnormalities was not significant compared with hypospadias (p = 0.3), genital ambiguity (p = 0.7) or cryptorchidism (p = 0.69), including nonpalpable testis (p = 1). When patients had karyotypic abnormalities, they were more likely to have proximal hypospadias (57.2%), palpable cryptorchidism (62.5%) and ambiguous genitalia (50%).

Most patients who present for the evaluation of hypospadias, chordee and undescended testis have a normal karyotype. Routine karyotype investigation of all patients with hypospadias, chordee and cryptorchidism does not seem warranted. If karyotypic intersex abnormalities are identified, those patients are more likely to have ambiguous genitalia, especially those with perineal hypospadias and cryptorchidism.