Clinical, Biological and Genetic Analysis of Anorchia in 26 Boys

Raja Brauner,Anu Bashamboo,Mathieu Neve,Slimane Allali,Christine Trivin,Henri Lottmann,Ken McElreavey,Joerg Gromoll

doi:10.1371/journal.pone.0023292

Abstract

BackgroundAnorchia is defined as the absence of testes in a 46,XY individual with a male phenotype. The cause is unknown.MethodsWe evaluated the clinical and biological presentation, and family histories of 26 boys with anorchia, and sequenced their SRY, NR5A1, INSL3, MAMLD1 genes and the T222P variant for LGR8.ResultsNo patient had any associated congenital anomaly. At birth, testes were palpable bilaterally or unilaterally in 13 cases and not in 7; one patient presented with bilateral testicular torsion immediately after birth. The basal plasma concentrations of anti-Müllerian hormone (AMH, n = 15), inhibin B (n = 7) and testosterone (n = 19) were very low or undetectable in all the patients evaluated, as were the increases in testosterone after human chorionic gonadotropin (hCG, n = 12). The basal plasma concentrations of follicle stimulating hormone (FSH) were increased in 20/25, as was that of luteinising hormone in 10/22 cases. Family members of 7/26 cases had histories of primary ovarian failure in the mother (n = 2), or sister 46,XX, together with fetal malformations of the only boy with microphallus and secondary foot edema (n = 1), secondary infertility in the father (n = 2), or cryptorchidism in first cousins (n = 2). The sequences of all the genes studied were normal.ConclusionUndetectable plasma concentrations of AMH and inhibin B and an elevated plasma FSH, together with 46,XY complement are sufficient for diagnosis of anorchia. The hCG test is unnecessary. NR5A1 and other genes implicated in gonadal development and testicle descent were not mutated, which suggests that other genes involved in these developments contribute to the phenotypes.

Highlights

Anorchia, or embryonic testicular regression, is defined as the absence of testes in a 46,XY individual with a male phenotype [1,2,3]
As the differentiation of the male genital tract and external genitalia is dependent on anti-Mullerian hormone (AMH) and testosterone, this suggests that functional testes were present, but disappeared in utero in these cases
The families of some patients with anorchia may include other individuals with pure or partial 46,XY gonadal dysgenesis. This has led to the suggestion that anorchia is part of the clinical spectrum of 46,XY gonadal dysgenesis [10]

Summary

Introduction

Embryonic testicular regression (vanishing testis syndrome), is defined as the absence of testes in a 46,XY individual with a male phenotype [1,2,3]. It affects one in 20,000 male births [4] and occurs in 1/177 cases of cryptorchidism [5]. The familial occurrence of anorchia [1,4,6,8] and its association with other anomalies [9] suggests a genetic origin, but the genetic cause remains unknown. The families of some patients with anorchia may include other individuals with pure or partial 46,XY gonadal dysgenesis.

Methods

Results

Discussion

Conclusion