A clinical case of an LHCGR gene mutation leading to Leydig cell hypoplasia and disordered sex development

Abstract

Disorders of sex development (DSD) are increasingly discussed in modern medicine. Advances in diagnostic methods have led to an increased identification of individuals with these conditions. This study presents a rare case of a patient with DSD and describes the treatment strategy. A male infant, aged 11 months, was admitted to the urology department for inpatient treatment with a diagnosis of 46XY DSD accompanied by suspected urogenital sinus and vaginal aplasia. According to the medical history, the child’s sex at birth could not be determined with certainty. Externally, the genitalia resembled female structures with incomplete feminization. Karyotyping confirmed a 46XY result. Physical examination in the pediatric hospital revealed that the external genitalia did not correspond to the karyotype. Bilateral, painless, and mobile gonad-like masses were palpated in the inguinal region. The urethral opening was located under a hypertrophied clitoris between hypoplastic labia minora. The labia majora exhibited transverse folds resembling a scrotum, and the vaginal introitus was absent. Whole-exome sequencing identified two mutations in the LHCGR gene. Diagnostic laparoscopy confirmed the absence of Müllerian and Wolffian duct remnants. A multidisciplinary medical council recommended that the parents raise the child as a female, and bilateral orchiectomy was performed. A feminizing genitoplasty is planned. This clinical case illustrates the management of a patient with DSD, emphasizing the key factors influencing treatment decisions. The availability of genetic testing in patients with DSD enables precise identification of the underlying cause, allowing for early adaptive surgical intervention, before the age of gender self-identification. Further analysis of these mutations and their clinical manifestations will contribute to improving the management of patients in this population.

Keywords

disorder of sex development / 46 XY / Leydig cell hypoplasia / LHCGR

References

[1] Jahan S, Abul Hasanat M, Alam F, et al. Leydig cell hypoplasia: a unique paradox in the diagnosis of 46, XY disorders of sex development. AACE Clinical Case Rep. 2020;6(3):e117–e122. doi: 10.4158/ACCR-2019-0152

[2] Jahan S., Abul Hasanat M., Alam F., et al. Leydig cell hypoplasia: a unique paradox in the diagnosis of 46, XY disorders of sex development // AACE Clin Case Rep. 2020. Vol. 6, N. 3. P. e117–e122. doi: 10.4158/ACCR-2019-0152

[3] García-Acero M, Moreno O, Suárez F, Rojas A. Disorders of Sexual Development: Current Status and Progress in the Diagnostic Approach. Curr Urol. 2020;13:169–178. doi: 10.1159/000499274

[4] García-Acero M., Moreno O., Suárez F., Rojas A. Disorders of Sexual Development: Current Status and Progress in the Diagnostic Approach // Curr Urol. 2020. Vol. 13. P. 169–178. doi: 10.1159/000499274

[5] Nikitina IL, Kudrjashova EK, Todieva AM, et al. K voprosu o svoevremennoj diagnostike narushenij formirovanija pola. Lechaschi Vrach. 2020;(3):17–21. (In Russ.) doi: 10.26295/os.2020.83.45.002

[6] Никитина И.Л., Кудряшова Е.К., Тодиева А.М., и др. К вопросу о своевременной диагностике нарушений формирования пола // Лечащий врач. 2020. № 3. С. 17–21. doi: 10.26295/os.2020.83.45.002

[7] Estermann MA, Smith CA. Applying Single-Cell Analysis to Gonadogenesis and DSDs (Disorders/Differences of Sex Development). Int J Mol. Sci. 2020;21(18):6614. doi: 10.3390/ijms21186614

[8] Estermann M.A., Smith C.A. Applying Single-Cell Analysis to Gonadogenesis and DSDs (Disorders/Differences of Sex Development) // Int J Mol Sci. 2020. Vol. 21, N. 18. P. 6614. doi: 10.3390/ijms21186614

[9] Yan M, Dilihuma J, Luo Y, et al. Novel Compound Heterozygous Variants in the LHCGR Gene in a Genetically Male Patient with Female External Genitalia. J Clin Res Pediatr Endocrinol. 2019;11(2):211–217. doi: 10.4274/jcrpe.galenos.2018.2018.0197

[10] Yan M., Dilihuma J., Luo Y., et al. Novel Compound Heterozygous Variants in the LHCGR Gene in a Genetically Male Patient with Female External Genitalia // J Clin Res Pediatr Endocrinol. 2019. Vol. 11, N. 2. P. 211–217. doi: 10.4274/jcrpe.galenos.2018.2018.0197

[11] Hall JE, Guyton AG. Medical Physiology according to Guyton and Hall. 2nd ed. Kobrin VI, Galagudza MM, Umryukhin AE, editors. Moscow: Logosfera; 2018. 1328 p. (In Russ.)

[12] Холл Дж.Э., Гайтон А.Г. Медицинская физиология по Гайтону и Холлу. 2-е изд. Под ред. Кобрина В.И., Галагудзы М.М., Умрюхина А.Е. Москва: Логосфера, 2018. 1328 с.

[13] Hassan HA, Essawi ML, Mekkawy MK, Mazen I. Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I. Hormones. 2020;19(4):573–579. doi: 10.1007/s42000-020-00226-6

[14] Hassan H.A., Essawi M.L., Mekkawy M.K., Mazen I. Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I // Hormones. 2020. Vol. 19, N. 4. P. 573–579. doi: 10.1007/s42000-020-00226-6

[15] Lee PA, Nordenström A, Houk CP, et al. Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care. Horm Res Paediatr. 2016;85(3):158–180. doi: 10.1159/000442975

[16] Lee P.A., Nordenström A., Houk C.P., et al. Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care // Horm Res Paediatr. 2016. Vol. 85, N. 3. P. 158–180. doi: 10.1159/000442975

[17] Radmayr C, Bogaert G, Burgu B, et al. EAU Guidelines on paediatric urology. European Association of Urology, 2023. 198 p.

[18] Radmayr C., Bogaert G., Burgu B., et al. EAU Guidelines on paediatric urology. European Association of Urology, 2023. 198 p.

RIGHTS & PERMISSIONS

Eco-Vector