Puberty strikes a discord: a rare case of Klinefelter syndrome — ASN Events
  1. Schedule
  2. Sex Steroids Cases
  3. Puberty strikes a discord: a rare case of Klinefelter syndrome

Puberty strikes a discord: a rare case of Klinefelter syndrome (#5)

Caitlin Corkhill 1 , Tim Greenaway 1 , Tony Lafferty 2
  1. Department of Endocrinology and Diabetes, Canberra Health Services, Garran, ACT, Australia
  2. Department of Paediatric Endocrinology and Diabetes, Canberra Health Services, Garran, ACT, Australia

Introduction

Klinefelter syndrome (KS) is the commonest sex chromosome aneuploidy, affecting 1 in 500-1000 males(1,2). >80% have the classical 47,XXY karyotype(1). Phenotype is variable and influences age at diagnosis. The majority are diagnosed after puberty onset(1) and ~30% in adulthood with symptomatic androgen deficiency or infertility(2). Minor KS karyotypes include: 48,XXXY, 48,XXYY, 49,XXXXY and the extremely rare 46,XX/47,XXY mosaic with 20 cases reported(3,4).

“Disorders/difference of sexual development (DSD)” is an umbrella term for congenital conditions of atypical chromosomal, gonadal or anatomical sex development(5,6).  We describe a rare case of DSD with 46,XX/47,XXY mosaic KS with gender-discordant puberty.

Case

J was born via caesarian-section for premature labour and transverse lie at 29 weeks’ gestation. Ambiguous genitalia were noted at birth: micropenis and severe hypospadias. Ultrasound confirmed gonads resembling testes and a cystic structure left the bladder, suggestive of Mullerian remnant. Lymphocyte chromosomal analysis scored 46% of cells 46,XX and 54% 47,XXY, diagnostic of mosaic KS.

Gonadotrophin and testosterone levels postnatal day 6 were consistent with normal neonatal pubertal surge with AMH in the male range.

Cystoscopy and laparoscopy found no obvious cervical/uterine tissue. Left inguinal exploration and orchidopexy report describes normal-appearing, small testis(<1ml) with normal epididymis.

Growth tracked along 25-50th centiles and mild developmental delay noted. External genitalia matured with testosterone treatment. At 2 years 3 months, penile length measured 3cm. Family described preferentially male behaviour. Staged surgery from age 3 included right orchidopexy, laparoscopic excision of Mullerian remnant/utricle and hypospadias repair. Bilateral gonadal biopsies showed prepubertal testis.

At 12 years 2 months, J had Tanner 3-4 pubic hair and stage 3 genitalia. Right testis was 6-7mL, left 2-3mL. Bilateral gynecomastia developed: 6-7cm discs of breast tissue with secondary areolar elevation. Ultrasound scrotum demonstrated a right testis. A heterogenous, ovoid structure was seen in the left hemi-scrotum inconsistent with normal testis.

  1. Bonomi, Marco, et al. "Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism." Journal of endocrinological investigation 40.2 (2017): 123-134.
  2. Radicioni, A. F., et al. "Consensus statement on diagnosis and clinical management of Klinefelter syndrome." Journal of endocrinological investigation 33.11 (2010): 839-850.
  3. Tangshewinsirikul, Chayada, et al. "Klinefelter Syndrome Mosaicism 46, XX/47, XXY: A New Case and Literature Review." Journal of Pediatric Genetics 9.04 (2020): 221-226.
  4. Pattamshetty, Preethi, Harika Mantri, and Vasavi Mohan. "Rare Disorder of Sexual Differentiation with a Mosaic 46, XX/47, XXY in a Klinefelter Syndrome Individual." Journal of Reproduction & Infertility 21.3 (2020): 222.
  5. Cools, Martine, et al. "Caring for individuals with a difference of sex development (DSD): a consensus statement." Nature Reviews Endocrinology 14.7 (2018): 415-429.
  6. Lee, Peter A., et al. "Global disorders of sex development update since 2006: perceptions, approach and care." Hormone research in paediatrics 85.3 (2016): 158-180.
  7. Lambert, Sophie, et al. "SRY‐negative 46, XX testicular/ovotesticular DSD: Long‐term outcomes and early blockade of gonadotropic axis." Clinical endocrinology 94.4 (2021): 667-676.
  8. Verkauskas, Gilvydas, et al. "The long-term followup of 33 cases of true hermaphroditism: a 40-year experience with conservative gonadal surgery." The Journal of urology 177.2 (2007): 726-731.
  9. Syryn, Hannes, Koen Van De Vijver, and Martine Cools. "Ovotesticular Difference of Sex Development: Genetic Background, Histological Features, and Clinical Management." Hormone Research in Paediatrics 94.7-8 (2021): 263-272.
  10. Variation in Sex Characteristics (Restricted Medical Treatment) Bill - Draft (ACT) 2022.