Challenges in clinical and laboratory diagnosis of androgen insensitivity syndrome: a case report

Caroline Oa Melo,Daniela M Silva,Aparecido D Da Cruz

doi:10.1186/1752-1947-5-446

Abstract

IntroductionAndrogen is a generic term usually applied to describe a group of sex steroid hormones. Androgens are responsible for male sex differentiation during embryogenesis at the sixth or seventh week of gestation, triggering the development of the testes and penis in male fetuses, and are directed by the testicular determining factor: the gene SRY (sex determining region on Y chromosome) located on the short arm of chromosome Y. The differentiation of male external genitalia (penis, scrotum and penile urethra) occurs between the 9th and 13th weeks of pregnancy and requires adequate concentration of testosterone and the conversion of this to another more potent androgen, dihydrotestosterone, through the action of 5α-reductase in target tissues.Case presentationThis report describes the case of a teenage girl presenting with a male karyotype, and aims to determine the extension of the mutation that affected the AR gene. A Caucasian girl aged 15 was referred to our laboratory for genetic testing due to primary amenorrhea. Physical examination, karyotype testing and molecular analysis of the androgen receptor were critical in making the correct diagnosis of complete androgen insensitivity syndrome.ConclusionsSex determination and differentiation depend on a cascade of events that begins with the establishment of chromosomal sex at fertilization and ends with sexual maturation at puberty, subsequently leading to fertility. Mutations affecting the AR gene may cause either complete or partial androgen insensitivity syndrome. The case reported here is consistent with complete androgen insensitivity syndrome, misdiagnosed at birth, and consequently our patient was raised both socially and educationally as a female. It is critical that health care providers understand the importance of properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a child with a pseudohermaphrodite phenotype should always undergo adequate endocrine and genetic testing to reach a conclusive diagnosis before gender is assigned and surgical interventions are carried out. Our results show that extreme care must be taken in selecting the genetic tools that are utilized for the diagnosis for androgen insensitivity syndrome.

Highlights

Androgen is a generic term usually applied to describe a group of sex steroid hormones
Our results show that extreme care must be taken in selecting the genetic tools that are utilized for the diagnosis for androgen insensitivity syndrome
The results reported in this paper underline the fact that great care must be taken when selecting genetic testing tools to be utilized to reach the proper diagnosis for androgen insensitivity syndrome (AIS)

Summary

Conclusions

We report that FISH alone was not able to properly diagnose our patient, despite the proximal deletion within the AR observed on PCR (Figure 3). This result could be explained by the size of the probe used (380 kb), which was bigger than the AR gene (90 kb), indicating that the deletion of some exons within the gene was not large enough to prevent probe hybridization (Figure 4) [11]. It is critical that health care providers understand the importance of properly diagnosing a newborn with ambiguous genitalia Prompt evaluation of both clinical and genetic findings is crucial to determine proper gender assignment and the detection of lifethreatening conditions [12]. Author details 1Pontifícia Universidade Católica de Goiás, Departamento de Biologia, Núcleo de Pesquisas Replicon, Goiânia, Goiás, Brazil. Competing interests The authors declare that they have no competing interests

Introduction

Findings

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