Hypospadias

Hypospadias is a congenital anatomical variation of the penis, consisting in the incomplete development of the urethra (the duct that carries urine from the bladder through the penis to the outside). The urethral seam is not in its usual location but anywhere on the penis, even near the scrotum or perineum (area between the scrotum and the anus). One of the most common anatomical variants of male genitalia, hypospadias occurs in about 1:250-1:300 children with XY chromosomes, although some data suggest a higher incidence. During the development of a fetus with 46,XY chromosomes, the differentiation into typically male genitalia depends on androgens (typically male hormones) produced by the testicles. Therefore, some cases of hypospadias may be caused by alterations in the production or action of androgens, and may be associated with other anatomical variants resulting in atypical genitalia. Most cases of hypospadias, especially mild/moderate forms, are not associated with hormonal alterations.

Genetic characteristics
Although hypospadias is usually a sporadic phenomenon, there is evidence that it tends to occur more frequently in certain families than others, which suggests that there are genetic factors underlying this anatomical variation. Both genes and environmental factors are likely to contribute to the development of hypospadias. Some Variations in Sex Characteristics (VSCs)/Differences of Sex Characteristic (DSDs) due to specific genetic mutations may occur along with hypospadias, as discussed above.

Background information
Hypospadias is diagnosed at birth by the pediatrician upon examining the infant. Children presenting hypospadias at birth will usually develop male sexual characteristics and normal fertility at puberty. In any case, a hormone test is often needed to rule out a possible defect in testosterone production or action, which in turn requires further studies, including genetic testing. Additionally, a urologic evaluation is typically recommended to rule out possible anatomic changes associated with hypospadias, which could be the cause of recurrent urinary obstructions and infections.

Medical options
The most recent guidelines recommend postponing any irreversible or partially reversible surgical procedure until the intersex person can express their informed consent. However, some anatomical variants may pose a risk to children's physical health, for example, in some cases of hypospadias, there may be obstructions in the urinary tract. Therefore, the recommendation to delay surgery applies to those anatomical variants that do not expose the person to immediate or long-term health risks. It is important that professionals and family consider both the benefits and risks of early surgery (6-18 months) as well as any actual alteration in organ function (generally absent in milder forms). Early intervention can have aesthetic and functional benefits, such as the ability to urinate in an upright position, and the optimization of the sexual and reproductive function in adulthood. However, there could be psychological risks, besides those related to anaesthesia and surgery itself. In most cases, one surgical intervention is enough but, in some more complex cases, two or more may be necessary. If the decision is to avoid surgery, professional support or counselling can help the child deal with their genital anatomy, by identifying possible sources of discomfort as well as solutions, including the option of reconsidering surgery. As an adult, a person with hypospadias may consult professionals about the best course of action to resolve specific health issues such as infertility, pain during sexual intercourse, inability to urinate in an upright position, and others.
 

Bibliography
Baskin LS et al. Urethral seam formation and hypospadias [Abstract]. Cell and tissue research. 2001 Sep;305(3):379-87
Beleza-Meireles A et al. Activating transcription factor 3: a hormone responsive gene in the etiology of hypospadias [Abstract]. European journal of endocrinology. 2008 May;158(5):729-39
Carmack A et al. Should surgery for hypospadias be performed before an age of consent? [Abstract] Jornal of Sex Research. 2016 Oct;53(8):1047-1058
Coleman E et al. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. International journal of transgender health. 2022 Sep 6;23(Suppl 1):S1-S259
Domenice S et al. 46,XY Differences of Sexual Development.  Last Update: 2022 Aug 21. In: Endotext [Internet]. Feingold KR et al. editors. DText.com, Inc: South Dartmouth (MA); 2000
Van der Horst HJ et al. Hypospadias, all there is to know. European Journal of Pediatrics. 2017 Apr;176(4):435-441

Further Links 
Centers for Disease Control and Prevention (CDC). Facts about Hypospadias
Ospedale Pediatrico Bambino Gesù. Ipospadia