USMLE® Step 1 style questions USMLE
A 15-year-old boy presents to his family physician for a routine school physical. The patient appears anxious and uneasy during the encounter. During the physical exam, the patient confesses that he feels insecure about his body. During gym practice, the patient has noticed that his genitalia appears different from his peers. There is no history of a disorder of sexual development within the family. The patient’s height and weight are at the 56th and 45th percentile for his age, respectively. On physical examination, ambiguous genitalia are present with a bifid scrotum, undescended testicles and hypospadias. Laboratory testing reveals an increased testosterone to dihydrotestosterone ratio. Which of the following is likely true regarding this patient’s parents?
5-alpha-reductase deficiency exam links
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS, Marisa Pedron, Brittany Norton, MFA, Antonia Syrnioti, MD
5α- reductase deficiency is a genetic disorder in which a protein called 5α reductase is defective or absent.
That’s an enzyme that converts the male hormone testosterone to its more potent form, called dihydrotestosterone.
One of the most important roles of dihydrotestosterone is to help male external genitalia develop in a male fetus.
Okay, normally, very early on in fetal life, male and female internal sex organs and external genitalia are undifferentiated and look identical.
Within the first few months of development, testes develop in the male fetus.
The testes start producing testosterone - a male steroid hormone that belongs to a class of hormones called androgens.
The testosterone gets released into the blood and a tiny fraction of it gets converted by 5α- reductase, which is mainly made in the skin of the genital area, into dihydrotestosterone.
Over time, dihydrotestosterone levels start rising and it affects undifferentiated genital structures.
Looking closely at these structures, at the top there’s the genital tubercle, which is a small projection.
Just below that, there's the urethral groove, which is the external opening of the urogenital sinus or the future urethra and bladder and is surrounded by the urethral folds and the labioscrotal swellings.
Now, once dihydrotestosterone reaches these structures, it makes the genital tubercle elongate into the phallus which will eventually be the penis.
The elongating genital tubercle pulls up the urethral folds which fuse in the midline, forming the spongy or penile urethra.
The tips of the urethral folds remain unfused and that forms the external urethral opening at the distal tip of the penis.
The labioscrotal swellings also fuse proximally to form the scrotum, which eventually houses the testes.
In females, the gonads develop into ovaries, which produce very low levels of androgens, so the genital tubercle remains small, forming the clitoris and the urethral folds and labioscrotal swellings remain unfused or separate, surrounding the opening of the vagina.
This process is usually complete by month four of fetal development.
In 5α- reductase deficiency there’s a mutation in the gene SRD5A2 and that reduces the amount of 5α- reductase enzyme that’s made.
The condition is inherited in an autosomal recessive but sex-limited pattern.
This means that for the disease to appear, both copies of the gene have to be mutated and the individual has to be genetically male, with one X and one Y chromosome in each cell, since dihydrotestosterone has no role in the development of genetically female individuals, with two X chromosomes in each cell.
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