Klinefelter Syndrome Flashcards
A 17-year-old male is brought to the clinic by his parents due to concerns about delayed puberty. On examination, he is tall and thin, with sparse facial and body hair. Testicular examination reveals small, firm testes bilaterally. Laboratory tests show a low testosterone level and elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Chromosomal analysis reveals a 47,XXY karyotype. Which of the following is the most likely diagnosis?
A) Turner syndrome
B) Androgen insensitivity syndrome
C) Noonan syndrome
D) Kallmann syndrome
E) Klinefelter syndrome
Answer: Klinefelter syndrome
Explanation: Klinefelter syndrome is the most common chromosomal disorder causing primary hypogonadism in males. It results from a 47,XXY karyotype due to nondisjunction during gametogenesis. Patients typically present with features of androgen deficiency, including tall stature, sparse body and facial hair, gynecomastia, and small, firm testes due to seminiferous tubule dysgenesis. The seminiferous tubule damage leads to impaired spermatogenesis, often resulting in infertility. The elevated gonadotropin levels (LH and FSH) are a compensatory response to testicular failure, and low testosterone levels contribute to the clinical phenotype. Diagnosis is confirmed with karyotype analysis.
Incorrect Answers:
A) Turner syndrome is a chromosomal disorder affecting females (45,X karyotype), associated with short stature, webbed neck, and ovarian dysgenesis.
B) Androgen insensitivity syndrome presents with a 46,XY karyotype and a female phenotype due to androgen receptor dysfunction.
C) Noonan syndrome can mimic Turner syndrome but is not associated with a chromosomal aneuploidy like 47,XXY.
D) Kallmann syndrome involves hypogonadotropic hypogonadism and anosmia, not hypergonadotropic hypogonadism seen in Klinefelter syndrome.
What is the karyotype associated with Klinefelter syndrome?
47,XXY (rarely 48,XXXY or 48,XXYY)
This is primarily due to nondisjunction of sex chromosomes.
Presence of a Barr body (inactivated X chromosome).
What increases the risk for developing Kleinfelter syndrome?
Advanced maternal age.
How common is Kleinfelter syndrome?
One of the most common causes of male hypogonadism.
occurs about 1 out of every 650 people in the US.
What are the common physical features of Klinefelter syndrome?
“Eunuchoidism”
- Tall stature and long limbs.
- Gynecomastia and female fat distribution (hips and chest).
- Female hair distribution.
- Small firm testes (low sperm counts) and micropenis.
What hormonal abnormalities are typically seen in Klinefelter syndrome?
Elevated FSH and LH.
Seminiferous tubules dysgenesis → loss of Sertoli cells → ↓ inhibin B → ↑ FSH
Leydig cell dysfunction → ↓ testosterone → ↑ LH
Low testosterone levels.
Both ↑ LH and ↑ FSH lead to increased conversion of testosterone to estrogen.
What psychosocial abnormalities are commonly associated with Klinefelter syndrome?
Increased risk of depression, anxiety, low self-esteem, social withdrawal, and difficulty forming relationships.
What is the most common cause of infertility in men with Klinefelter syndrome?
Testicular atrophy leading to azoospermia.
There’s an increase for developing testicular cancer.
Testicular biopsies can be performed after puberty showing seminiferous tubule fibrosis and leydig cell hyperplasia.
What are the main components of management for Klinefelter syndrome?
Testosterone replacement therapy, psychosocial support, fertility counseling, and regular screening for associated complications.
What are the common complications associated with Klinefelter syndrome?
Mitral valve prolapse.
Osteoporosis.
Metabolic syndrome and type 2 diabetes.
Increased risk of breast cancer.
Increased risk of testicular cancer.
How does Klinefelter syndrome typically present in adulthood?
Infertility, gynecomastia, female fat distribution, low libido, reduced muscle mass, and psychosocial issues.
What diagnostic test confirms Klinefelter syndrome?
Karyotype analysis showing 47,XXY.
Why do individuals with Klinefelter syndrome have gynecomastia?
Due to an imbalance of estrogen and testosterone levels.
↑ aromatase and ↑ estrogen levels.
What cognitive or developmental features might be seen in Klinefelter syndrome?
Mild learning disabilities, delayed speech and language development, and social adjustment difficulties.
Impaired executive function and memory, decreased intelligence.
Neurocognitive developmental delay becomes increasingly severe with each additional X chromosome.
Poor social skills.
What is the long-term management focus for Klinefelter syndrome?
Hormonal therapy, bone density monitoring, regular cancer screenings, fertility preservation options, and psychological counseling to address emotional and social challenges.
Lifelong testosterone improves the development of secondary sexual characteristics, prevents gynecomastia, and prevents the development of osteoporosis.
