Kallmann Syndrome Flashcards
A 17-year-old male is evaluated for delayed puberty. He reports a lack of facial and body hair, no voice deepening, and poor muscle development despite being active in sports. On further questioning, he mentions difficulty identifying smells. Physical examination reveals decreased testicular volume and cryptorchidism. Laboratory findings show low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Karyotype analysis is 46,XY. Which of the following is the most likely diagnosis?
A) Klinefelter syndrome
B) Androgen insensitivity syndrome
C) Kallmann syndrome
D) Turner syndrome
E) 5-alpha-reductase deficiency
Answer: Kallmann syndrome
Explanation: Kallmann syndrome is a genetic condition characterized by hypogonadotropic hypogonadism and anosmia or hyposmia. It results from defective migration of GnRH-releasing neurons to the hypothalamic preoptic nucleus, leading to decreased GnRH secretion. This causes a downstream reduction in FSH, LH, and testosterone levels, resulting in absent or incomplete pubertal changes such as lack of facial/body hair, no voice changes, and poor muscle development. Cryptorchidism and anosmia are hallmark features. The karyotype is typically 46,XY in males or 46,XX in females.
Incorrect Answers:
A) Klinefelter syndrome: Features include a 47,XXY karyotype, tall stature, gynecomastia, and small firm testes, not anosmia or cryptorchidism.
B) Androgen insensitivity syndrome: A 46,XY karyotype with a female phenotype and sparse pubic hair is characteristic, but anosmia is not a feature.
D) Turner syndrome: Affects 45,X individuals and is associated with short stature, webbed neck, and ovarian dysgenesis, not cryptorchidism or anosmia.
E) 5-alpha-reductase deficiency: Causes ambiguous genitalia in 46,XY individuals and virilization during puberty, but anosmia is not seen.
What is the prevalence of Kallmann syndrome?
3:100,000 male and 0.8:100,000 female population in the US
- very rare -
What are the karyotypes associated with Kallmann syndrome?
46,XY or 46,XX
What is the etiology of Kallmann syndrome?
Associated with more than 20 different gene mutations.
Result in hypogonadotropic hypogonadism with anosmia or hyposmia.
What is the pathophysiology of Kallmann syndrome?
Defective migration of GnRH-releasing neurons from the olfactory bulbs to the hypothalamic preoptic nuclei, leading to decreased GnRH secretion, underdeveloped olfactory bulbs, and subsequent decreased FSH, LH, testosterone, and estrogen secretion.
What are the hallmark clinical features of Kallmann syndrome?
Anosmia or hyposmia, infertility, cryptorchidism, primary amenorrhea, and osteoporosis.
What pubertal changes are absent or attenuated in Kallmann syndrome?
Decreased growth spurt, reduced or absent facial/body hair, lack of voice changes, no muscle bulk (males), reduced or no axillary hair, absent thelarche (females)
What associated conditions are commonly seen in Kallmann syndrome?
Renal agenesis, cleft lip/palate, dental agenesis, syndactyly, hearing loss
What are the characteristic hormone abnormalities in Kallmann syndrome?
Decreased levels of GnRH, FSH, LH, estrogen/testosterone (otherwise normal pituitary function)
What diagnostic methods are used to confirm Kallmann syndrome?
Clinical presentation and hormone level testing (GnRH, FSH, LH, estrogen/testosterone)
What are the main treatment options for Kallmann syndrome?
Hormone replacement therapy (testosterone in males; estrogen and progesterone in females), pulsatile GnRH therapy, gonadotropins to induce fertility
