Background: A normal sex development and appropriate sex assignment take place when sex chromosomes, gonadal histology and genital phenotype are concordant.
A disorder of sex development (DSD) is defined whenever a discordance between two of the aforementioned features is found.
DSDs can be caused by an alteration in the chromosomal complement, or by an abnormal development of the gonads, by a defect in one of the enzymatic pathways for the synthesis of sex hormones or by the absence (or altered structure) of hormone receptors.
In the majority of cases, DSD is heralded by ambiguity of the external genitalia that generally speaking is the result either of a hypervirilization of a 46, XX individual or of a hypovirilization of a 46, XY individual. However, there are cases of DSD in which the genital phenotype is not ambiguous. Those cases are the most difficult to diagnose and are sometimes identified at puberty when unexpected development of secondary sexual characters or primary amenorrhea are observed.
When an obvious ambiguity of the external genitalia is not found, the presence of a DSD should be suspected whenever a newborn with apparent male phenotype shows one of the following features (bilateral impalpable gonads, unilateral undescended testis associated with hypospadias, isolated perineal hypospadias, bifid scrotum) or when an apparent female newborn shows a gonad palpable in a hernia sac, hypertrophied clitoris or fused small labia: such findings should prompt investigation in order to rule out a possible DSD.
Karyotype is key in the diagnosis of suspected DSD. Next step is defining the presence/absence of Müllerian remnants with ultrasound or MRI. At this point, most of the DSD due to an enzymatic defect can be identified by means of hormonal tests (either basal levels or stimulation tests). In the remaining cases in which hormonal tests are not diagnostic, a gonadal biopsy is mandatory to identify a gonadal dysgenesis, an ovotesticular DSD (former hermaphroditism), or a sex reversal.
In cases in which gonads are not palpable, laparoscopy is the gold standard to define their presence, site and macroscopic appearance. It is also very easy to perform a laparoscopic gonadal biopsy and gonadal removal in cases of streak gonads. Finally, laparoscopy is an invaluable tool for the examination of the internal genitalia: it adds useful information to the data obtained by imaging studies and consequently allowing for planning of the definitive treatment.
The video shows a DSD patient in whom laparoscopic gonadal biopsies and left gonadectomy were performed.
Video: A 9-month-old baby with ambiguous genitalia was referred to our centre for evaluation. A female sex assignment was given at birth. At clinical examination, clitoral hypertrophy was evidenced, with a single perineal orifice; the left gonad was palpable in the groin and the right one was non-palpable. No inguinal hernias were detected. Testosterone levels at birth were high (95.8ng/mL) and this finding persisted throughout infancy. The chromosomal complement was 46 XY. Analysis of the AR gene was negative. MRI examination showed the presence of uterus (35 x 10mm); both gonads were visualized in the inguinal region. Laparoscopic gonadal biopsy was decided upon. A 5mm port was placed at the umbilicus through an open access. Pneumoperitoneum was established: carbon dioxide was insufflated at 1L/min and intra-abdominal pressure was set at 8mmHg. Two 3mm operating ports were placed in the right and left iliac fossa.
The presence of a normally developed uterus was confirmed; the right gonad resembled a normal ovary; on the left side, a patent processus vaginalis and an atypical round gonad with a regular surface were observed. Both gonads were biopsied and frozen sections examinations revealed a normal ovary on the right and an ovotestis on the left. Left gonadectomy ensued after monopolar division of the gonadal vessels. The specimen was extracted through the umbilicus.
Results: No conversion to open surgery nor additional trocars were necessary. Total operative time was 120 minutes (including histological examination); biopsy time was 5 minutes for each side; gonadectomy took 15 minutes. No drainage was required. The postoperative course was uneventful and the patient was discharged on day 2.
Conclusion: Laparoscopy in DSD cases is a valuable diagnostic tool in selected patients. It allows gonadal visualization and biopsy together with complete examination of Müllerian derivatives.