Hypospadias refers to a birth defect of the urethra in the male where the urinary opening is not at the usual location on the head of the penis. These malformations mainly comprise of an abnormal ventral opening of the urethral meatus, an abnormal ventral curvature of the penis (chordee) and/or an abnormal distribution of the foreskin. The extent of the malformation varies.

Such ectopic urethral openings (meatus) can be located at the tip of the glans penis (hypospadia sine hypospadia), glanular, coronal, subcoronal, along the penile shaft, penoscrotal, scrotal, or perineal. The form and extent of malformation of the urethral opening varies as well and is in some cases widely gaping and resembling the mouth of a fish. A stenosis is rather rare.

Further abnormalities in hypospadia concern the prepuce. Typically, there is a dorsal hump with excessive skin on the dorsal and a scarcity of foreskin on the ventral aspect of the penis. In most cases, the frenulum (an elastic band of tissue under the glans penis that connects the foreskin (prepuce) to the vernal mucosa, and helps contract the foreskin over the glans) is entirely missing. In the rare cases when the prepuce is normally developed, it must be preserved and a circumcision avoided.

The prevalence of hypospadia is around 0.3-0.8%, making it the most frequently occuring male external genitalia congenital malformation. The pathogenesis of hypospadias is uncertain, but there are several risk factors associated with the onset of hypospadias such as genetic, environmental and endocrine factors. Babies of young and older mothers and the low birth weight babies are at risk for the occurrence of hypospadias. A significant increase of the incidence of hypospadias in last 20 years shows the role of environmental factors such as hormonal and pesticides. 

Surgery to repair anatomical defect is the only treatment for hypospadias. The aim of surgical correction is to achieve: (1) a cosmetically acceptable penile shaft, glans, and meatus; (2) allow a straight forward-directed urinary stream; and (3) a straight penis on erection for adequate sexual function.

Reproduction system related disorders:

  • Undescended testes
  • Klinefelter syndrome
  • Hypogonadism
  • XX male syndrome

Undescended testes

Hypospadias may be accompanied by different genital malformations. The frequency of associated anomalies increases with the severity of hypospadias. Cryptorchidism (undescended testicles) and inguinal hernia are the most commonly associated anomalies.

Klinefleter syndrome

The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism.


The luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis. In the male the LHR has been identified on the Leydig cells that are critical for testosterone production, and support spermatogenesis.

Normal LHR functioning is critical for male fetal development, as the fetal Leydig cells produce testosteroneto induce masculinization. Hypogonadotropic hypogonadism is a condition which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including luteinizing hormone (LH), by the pituitary gland in the brain, and in turn decreased gonadotropin levels and a resultant lack of sex steroid production.

Inactivating mutations of luteinizing hormone receptor are present in all domains of the receptor. As a result, there may be partial inactivation or complete loss of receptor function. Milder form, caused by mutations that allow partial LHR function, results in micropenis and hypospadia. 

XX male syndrome

46, XX male syndrome is a rare sex reversal syndrome (SRY) characterized by a female karyotype in discordance with a male phenotype. SRY gene is located in the Y chromosome and encodes a domain, present in many DNA-binding proteins, which could regulate testicular differentiation. SRY protein is expressed in the genital ridge before testis formation, and in the testis during the period of testicular formation early in fetal life, until the development of adult testis. Molecular genetics analysis demonstrated that most 46, XX patients carry SRY gene which translocated to X chromosome. The phenotype of the XX male observed in SRY positive 46,XX individuals varies greatly, from normal internal and external male gonads to abnormal secondary sexual characteristics, small testes and hypospadias, to a true hermaphrodite.

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Klinefelter syndrome and other sex chromosomal aneuploidies ―by Visootsak and Graham licensed under CC BY 2.0
Hypogonadotropic hypogonadism ―sourced from Wikipedia licensed under CC BY- SA 3.0
Hypospadias ―by Djakovic et al. licensed under CC BY 3.0
Frenulum of prepuce of penis ―sourced from Wikipedia licensed under CC BY- SA 3.0
Luteinizing hormone/choriogonadotropin receptor ―sourced from Wikipedia licensed under CC BY- SA 3.0
Penis with hypospadia ―by Buddy I Con licensed under CC0
Hypospadia ―by Quercus07 licensed under CC BY- SA 3.0
Types of hypospadia ―sourced from Wikipedia licensed under CC0
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