18-Year-old patient with Klinefelter syndrome (47, XXY) and complete androgen insensitivity syndrome (CAIS) – case report

Abstract Aims The aims of the presented case report are to emphasize the importance of a proper diagnostics and treatment in the case of the coexistence of Klinefelter syndrome (KS, 47 XXY) and complete androgen insensitivity syndrome (CAIS). Since there is no causal treatment it is necessary to provide the patient with a good quality of life, including psychological and sexological support. Materials and methods The presented case report is the retrospective analysis of the patient’s medical history over the 3 years. Results At the age of 15, the patient was directed to genetic testing due to primary amenorrhea. The results of the patient showed an incorrect male karyotype with the SRY gene present (47, XXY). A molecular diagnostics revealed a very rare variant of the androgen receptor (AR) mutation responsible for tissue insensitivity to androgens. The detected mutation has not been described in the available databases so far. Following a diagnosis of the presence of Klinefelter syndrome (KS, 47 XXY) together with complete androgen insensitivity syndrome (CAIS), the patient underwent a bilateral gonadectomy. Conclusions In women with KS and CAIS physiological reproduction and maintenance of normal sex, hormone levels are not possible. A gonadectomy is performed due to the risk of malignant testicular tumors.

[1]  R. Płoski,et al.  Rapid Whole-Exome Sequencing as a Diagnostic Tool in a Neonatal/Pediatric Intensive Care Unit , 2020, Journal of clinical medicine.

[2]  Weber Dm,et al.  Complete Androgen Insensitivity Syndrome (CAIS) and Karyotype 47, XXY, with Sertoli-Leydig Cell Tumor: Description of a Rare Case , 2019 .

[3]  Mostafa El-Feky.  Androgen insensitivity syndrome. , 2019, Bailliere's clinical endocrinology and metabolism.

[4]  A. Sobczyńska-Tomaszewska,et al.  Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1 , 2019, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  S. Esposito,et al.  Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS) , 2019, International journal of environmental research and public health.

[6]  D. Sherman,et al.  Homozygous mutation in the Neurofascin gene affecting the glial isoform of Neurofascin causes severe neurodevelopment disorder with hypotonia, amimia and areflexia , 2018, Human molecular genetics.

[7]  I. Arnhold,et al.  Androgen insensitivity syndrome: a review , 2018, Archives of endocrinology and metabolism.

[8]  L. Wünsch,et al.  Gonadectomy in Complete Androgen Insensitivity Syndrome: Why and When? , 2017, Sexual Development.

[9]  L. Looijenga,et al.  Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome , 2017, Sexual Development.

[10]  G. Baroncelli,et al.  Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads , 2017, Sexual Development.

[11]  C. Foresta,et al.  Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations? , 2017, Scientific Reports.

[12]  T. Fujiwara,et al.  Complete androgen insensitivity syndrome and anti-Müllerian hormone levels before and after laparoscopic gonadectomy , 2016, Gynecology and minimally invasive therapy.

[13]  C. Gravholt,et al.  Klinefelter syndrome and medical treatment: hypogonadism and beyond , 2015, Hormones.

[14]  A. Lteif,et al.  Development of the Human Breast , 2013, Seminars in Plastic Surgery.

[15]  D. Kotzot,et al.  Chromosomal Variants in Klinefelter Syndrome , 2011, Sexual Development.

[16]  E. Lemyre,et al.  Molecular studies of a patient with complete androgen insensitivity and a 47,XXY karyotype. , 2009, The Journal of pediatrics.

[17]  G. Frank.  Role of estrogen and androgen in pubertal skeletal physiology. , 2003, Medical and pediatric oncology.

[18]  F. E. Eyben.  Laboratory Markers and Germ Cell Tumors , 2003 .

[19]  P. D. Semple.  KLINEFELTER'S SYNDROME , 1977, The Medical journal of Australia.

[20]  H. Jones,et al.  The age of occurrence of gonadal tumors in intersex patients with a Y chromosome. , 1976, American journal of obstetrics and gynecology.

[21]  P. Jacobs,et al.  A Case of Human Intersexuality Having a Possible XXY Sex-Determining Mechanism , 1959, Nature.

[22]  C. Gravholt,et al.  Clinical review: Klinefelter syndrome--a clinical update. , 2013, The Journal of clinical endocrinology and metabolism.

[23]  I. Hughes,et al.  Androgen resistance. , 2006, Best practice & research. Clinical endocrinology & metabolism.

[24]  H. Maibach,et al.  Lifetime changes in the vulva and vagina , 2005, Archives of Gynecology and Obstetrics.

[25]  F. V. von Eyben.  Laboratory markers and germ cell tumors. , 2003, Critical reviews in clinical laboratory sciences.