Disorders of sex development: timing of diagnosis and management in a single large tertiary center

Abstract

BackgroundWe describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center.MethodsDSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts.ResultsAmong the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001).ConclusionsOur results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients’ adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Controversies on Timing of Sex Assignment and Surgery in Individuals With Disorders of Sex Development: A Perspective

“…In patients with complete androgen insensitivity syndrome (CAIS), conservative management of gonads is suggested until puberty, as there is a small risk of malignancy (27). Furthermore, in patients assigned as boys, the time for orchidopexy has decreased significantly after the 2006 consensus (from 54.5 ± 43.0 months to 41.4 ± 45.3 months) (32).…”

Onset and progression of puberty in Klinefelter syndrome

“…KS is highly underdiagnosed due to large phenotypic variation. According to some studies, less than half of the males with KS become diagnosed during their lifetime 1,3,4 . In our unit, the average age at diagnosis of KS was 6.7 years 4 .…”

“…According to some studies, less than half of the males with KS become diagnosed during their lifetime 1,3,4 . In our unit, the average age at diagnosis of KS was 6.7 years 4 . Only a minority of boys with KS are diagnosed prenatally, usually due to suspicion of other chromosome disorders than KS 5 .…”

The Evaluation of Parental Acceptance Towards Children with Sex Chromosomal Disorders of Sex Development Using A Mixed-Method

“…But, in adolescents, the condition is identified with symptoms of an inguinal hernia in the female, late or incomplete puberty, virilization in the female, primary amenorrhea, breast growth in males, and a previously unknown ambiguous genitalia. 24 In cases of sex chromosome mosaicisms, the question is often about the gender assignment, the right time for surgery, and the potential for gonadal malignancy. 26 Enforcement of early DSD diagnosis is considered important, and diagnostic procedures efficacy often requires evaluation based on the child's developmental stages.…”

“…26 Enforcement of early DSD diagnosis is considered important, and diagnostic procedures efficacy often requires evaluation based on the child's developmental stages. 24 In Indonesia, this health condition is not widely known by both health workers and the common population, while clinical treatment is a challenge because of limited diagnostic and therapeutic facilities. Consequently, many patients experience delays in diagnosis, 27 but treatment in children reduces parental anxiety about their condition and possible stigmatization due to these abnormalities.…”