Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS)

Abstract

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive genetic disorder resulting from maternally inherited or de novo mutations involving the androgen receptor gene, situated in the Xq11-q12 region. The diagnosis is based on the presence of female external genitalia in a 46, XY human individual, with normally developed but undescended testes and complete unresponsiveness of target tissues to androgens. Subsequently, pelvic ultrasound or magnetic resonance imaging (MRI) could be helpful in confirming the absence of Mullerian structures, revealing the presence of a blind-ending vagina and identifying testes. CAIS management still represents a unique challenge throughout childhood and adolescence, particularly regarding timing of gonadectomy, type of hormonal therapy, and psychological concerns. Indeed this condition is associated with an increased risk of testicular germ cell tumour (TGCT), although TGCT results less frequently than in other disorders of sex development (DSD). Furthermore, the majority of detected tumoral lesions are non-invasive and with a low probability of progression into aggressive forms. Therefore, histological, epidemiological, and prognostic features of testicular cancer in CAIS allow postponing of the gonadectomy until after pubertal age in order to guarantee the initial spontaneous pubertal development and avoid the necessity of hormonal replacement therapy (HRT) induction. However, HRT is necessary after gonadectomy in order to prevent symptoms of hypoestrogenism and to maintain secondary sexual features. This article presents differential clinical presentations and management in patients with CAIS to emphasize the continued importance of standardizing the clinical and surgical approach to this disorder.

46, XY disorder of sex development (DSD) complicated by a serous borderline tumor of the ovary: a case report and review of the literature

“…Surgical resection of dysplastic gonads is currently the best way to prevent tumorigenesis or the malignant transformation of benign tumors. However, gonadectomy can be postponed until after puberty to ensure that puberty progresses and to avoid the influence of hormone replacement therapy on the patient's body [8]. In our case, the streak ovary formed the basis for a serous borderline tumor; ovariectomy was effectively able to prevent exacerbation of the tumor.…”

Malignant Germ Cell Tumors and Their Precursor Gonadal Lesions in Patients with XY-DSD: A Case Series and Review of the Literature

“…In order to ensure the right diagnosis, molecular characterization should be performed in patients with XY-DSD. Genetic analysis at an early timepoint is vital to establish endocrinological and surgical therapy as soon as possible [ 45 ]. This fact also limits the power of our study, as karyotyping was performed in every patient, yet molecular characterization was done in only 15 patients (43%) in total.…”

The challenges of androgen insensitivity syndrome

“…• Contains a polymeric amino acid region that includes glycine and glutamine repeats (GGN and CAG) • Contains the transactivation function 1 region (AF1), known as transcription activation unit 1 (TAU1) [11][12][13] • Involved in the transcription regulation process • Its length interferes with AR transcription activity • Extensive deletions of this first domain are responsible for the decrease of the transactivation process • FxxLF (F -phenylalanine, L -leucine, x -any other amino acid) acts as a coactivator in the transcription activation process • The length of the polyglutamine region correlates with the risk of genital anomalies and also with the risk of prostate cancer (when the polyglutamine repeat region is shorter) [11][12][13] • A larger polyglutamine repeat seems to be associated with the risk of Kennedy disease, which consists in spinal bulbar muscular atrophy [14] DNA-binding domain (DBD) • Encoded by exons 2 and 3 • Presents 2 zinc protein modules, the first being involved in establishing the contact with the DNA, while the second modulates this interaction and the DNA dimerization process • The structure depends on the interaction between cysteine and the zinc ion.…”