Which of the following is implicated in the development of this patient\'s underlying condition?

A 15-year-old male comes to his doctor worried that he has not yet gone through puberty. He feels that his genitals are less developed than they should be for his age. On physical exam, you note an absence of facial hair and that his voice has not yet deepened. Your exam confirms that he is Tanner Stage 1. On a thorough review of systems, you learn that the patient has lacked a sense of smell from birth. Which of the following is implicated in the development of this patient’s underlying condition?

1.Chromosomal dupication
2.Exposure suprasellar tumor
3.Exposure of normal neuronal migration during development
4.Failure of neuronal migration during development
5.Defect in steroid production

This clinical presentation is consistent with Kallmann syndrome, a type of hypogonadotropic hypogonadism associated with anosmia that results from failure of GnRH-secreting neurons to migrate from the olfactory placode, through the cribriform plate and olfactory bulb, and into the hypothalamus.
A lack of pulsatile GnRH in Kallmann syndrome leads to decreased levels of LH/FSH produced by the anterior pituitary, and a concomitant decline in testosterone production by the testes. Kallmann syndrome involves delayed puberty and anosmia, or an inability to smell, as well as other potential congenital abnormalities (mid-line defects, renal agenesis, or skeletal abnormalities). Laboratory analysis will show low levels of LH/FSH and testosterone, an important finding that distinguishes Kallmann’s syndrome from forms of hypergonadotrophic hypogonadism.

Illustration A depicts the important GnRH-FSH/LH-testosterone axis that is disrupted in Kallman’s syndrome, along with the resulting clinical effects.