Hypospadias

Incidence

The incidence of hypospadias has been estimated between 0.8 and 8.2 per 1000 live male births. In Europe the prevalence of hypospadias is estimated at 18.6 per 10,000 births, while in North America this is 34.2 per 10,000 births. The lowest prevalence is in Asia at 0.7 per 10,000 births. This wide variation probably represents geographic and racial differences, but of more significance is likely the exclusion of the more minor degrees of hypospadias in some reports. If all degrees of hypospadias, even the most minor, are included, it is likely that the incidence is probably 1 in 125 live male births. With the most quoted figure of 1 per 200–300 live male births, it can be assumed that more than 6000 boys are born with hypospadias each year in the United States.

Etiology

The etiology of isolated hypospadias without associated disorders of sexual differentiation (DSD) is unclear. Many theories have been proposed to explain the etiology of hypospadias. Genetic factors, inadequate hormonal stimulation, maternal/placental factors, and environmental factors have all been implicated. It is likely that a combination of all these factors play a role in the development of hypospadias.

Deficient androgen production by the testes, failure of 5α-reductase enzyme to convert testosterone to dihydrotestosterone, insufficient hCG production by the placenta, or faulty androgen receptors in the genitalia can, in part, explain the development of hypospadias. Various DSD are associated with hormone deficiencies or derangements that lead to hypospadias or hypospadias variants. An endocrine cause has been implicated in some reports that show a diminished response to hCG in some patients with hypospadias, suggesting delayed maturation of the hypothalamic–pituitary axis and poor hormonal stimulation during the early crucial weeks of development. Other reports have described an increased incidence of hypospadias in monozygotic twins, suggesting an insufficient amount of hCG production by the single placenta to accommodate the two male fetuses. This has been further supported by linking maternal hypertension to an increased risk of hypospadias. In utero exposure to certain medications (e.g., valproate, loperamide, paroxetine, and estrogenic or anti-androgenic medications) have been associated with an increased risk of hypospadias. A weak association between hypospadias and the maternal exposure to progestin-like agents has also been reported. However, no association has been found between hypospadias and oral contraceptive use before or during early pregnancy. Interestingly, there appears to be a higher incidence of hypospadias with winter conceptions.

A large number of genes have been implicated in hypospadias. A genetic predisposition is highly suggested given the high incidence of this anomaly in first-degree relatives, with 7–10% of cases having an affected relative. However, only 30% of isolated hypospadias cases have an identifiable genetic cause, and most are idiopathic. The heritability of hypospadias can range between 55% and 75% with no difference between maternal and paternal transmission. In one study that evaluated 307 families with hypospadias, the risk of hypospadias in a second male sibling was 12%. If the index child and his father were affected, the risk for a second sibling increased to 26%. If the index child and a second-degree relative (rather than the father) were affected, the risk of the sibling being affected was 19%. This pattern suggests a multifactorial mode of inheritance and penetrance. Hypospadias has been associated with multiple genetic disorders and syndromes, most notably WAGR syndrome (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) and Denys–Drash syndrome (genitourinary malformations and susceptibility to Wilms tumor). Both syndromes are associated with WT1 gene mutations.

Anatomy of the Defect

The clinical significance of hypospadias is related to several factors. The abnormal location of the meatus and the tendency toward meatal stenosis result in a ventrally deflected and splayed stream. These factors make the stream difficult to control and often make it difficult for the patient to void while standing. The ventral curvature associated with chordee can lead to painful erections, especially with severe chordee. These can lead to impaired copulation due to the chordee and thus inadequate insemination. In addition, the unusual cosmetic appearance associated with the hooded foreskin, flattened glans, and ventral skin deficiency frequently has an adverse effect on the psychosexual development of the adolescent with hypospadias. These factors should be discussed and considered when determining timing and indication for surgical correction of hypospadias, regardless of the severity of the defect.

The distal form of hypospadias is the most common (see Box 59.1 ). Frequently, little or no associated chordee is present ( Fig. 59.1 ). The size of the meatus and the quality of the surrounding supportive tissue as well as the configuration of the glans can be variable, and ultimately determine the appropriate operative approach for each patient. Well-formed, mobile perimeatal skin and a deep ventral glans groove may allow development of perimeatal flaps to create the urethra ( Fig. 59.2 ). In contrast, atrophic and immobile skin around the meatus may require tissue transfer, typically from the prepuce or other donor sites, to form a neourethra ( Fig. 59.3 ).

An unusual variant of the distal hypospadias is the large wide-mouthed meatus with a normal appearing circumferential foreskin (the megameatus intact prepuce variant) ( Fig. 59.4 ). Owing to the intact prepuce, this variant is often not identified until a circumcision is attempted or performed. Historically, clinicians have opted not to perform a newborn circumcision if a hypospadias is discovered after a dorsal slit is created and the glans is exposed. This thinking has recently been questioned, as most patients with complete prepuce have a very mild form of hypospadias, most of which require no intervention or can be repaired without the use of the prepuce.

At times, the distally located meatus may be associated with significant chordee, sometimes of a severe degree ( Fig. 59.5 ). The release of the chordee can result in a much more proximal location of the meatus, requiring a more complicated repair to bridge the gap between the proximal meatus and the tip of the glans. When the meatus is located on the penile shaft, the character of the urethral plate (midline ventral shaft skin distal to the meatus) is important in determining what type of repair is possible. A well-developed and elastic urethral plate suggests minimal, if any, distal ventral curvature ( Fig. 59.6 ). However, a thin atrophic urethral plate heralds a significant chordee. The proximal supportive tissue of the urethra also is important. If there is a lack of spongiosum proximal to the hypospadiac meatus, this portion of the native urethra is not substantial enough to be used in the repair ( Fig. 59.7 ). Therefore, the neourethra must be constructed from the point of adequate spongiosum by cutting back.

The position of the meatus at the penoscrotal, scrotal, or perineal location is usually associated with severe chordee, which requires chordee release and an extensive urethroplasty ( Fig. 59.8 ). This type is usually more predictable in the preoperative period as to the choice of technique than are some of the more distal types previously discussed. Other anatomic elements of the anomaly that are important include penile torsion, glans tilt, penoscrotal transposition, and chordee without hypospadias. These are discussed in more detail later in the chapter.

Associated Anomalies

Inguinal hernia and undescended testes are the most common anomalies associated with hypospadias. They occur in 7–13% of patients with a greater incidence when the meatus is more proximal. An enlarged prostatic utricle also is more common in proximal hypospadias, with an incidence of about 10%. Infection is the most common complication of a utricle, but excision is rarely necessary. Several reports have emphasized significantly high numbers of upper urinary tract anomalies associated with hypospadias, suggesting that routine upper tract screening is necessary. However, when the association is stratified by degree of hypospadias, it is evident that the types of hypospadias at risk for significant upper tract anomalies are the penoscrotal and perineal forms, and those associated with other syndromes or organ system abnormalities. When one, two, or three other organ system abnormalities are associated with hypospadias, the incidence of significant upper tract anomalies is 7%, 13%, and 37%, respectively. Associated myelomeningocele and imperforate anus carry a 33% and 46% incidence, respectively, of upper urinary tract malformations. In isolated proximal hypospadias, the incidence of associated upper tract anomalies is under 5%.

In midshaft and distal hypospadias, when not associated with other organ system anomalies, the incidence is similar to that in the general population. Therefore, it is recommended that screening for upper urinary tract abnormalities with renal ultrasonography and/or voiding cystourethrogram (VCUG) be performed only in patients with proximal hypospadias (i.e., penoscrotal and perineal), and in those with anomalies associated with at least one additional organ system. Screening should also be done in patients with other known indications, such as a history of urinary tract infection, upper or lower tract obstructive symptoms, hematuria, and in those boys having a strong family history of urinary tract abnormalities.

Males with DSD often have associated hypospadias, but the majority of isolated hypospadias are rarely associated with DSD. When hypospadias is associated with undescended testes, micropenis, penoscrotal transposition (see Fig. 59.5 ), or bifid scrotum (see Fig. 59.8 ), DSD should be considered and warrants evaluation with karyotype along with evaluation by a multidisciplinary team with expertise and interest in DSD.

Age at Repair

The technical advances over the past few decades have made it possible to repair hypospadias in the first 6–12 months of life in most patients. Some surgeons have suggested delaying repair until after the child is 2 years of age. However, most surgeons who deal routinely with hypospadias prefer to perform the repair when the patient is 6–12 months old. One study compared the emotional, psychosexual, cognitive, and operative risks for hypospadias. The “optimal window” recommended for repair was age 6–15 months. There is also evidence that healing may be better with decreased inflammatory factors and less scarring in the <6-month age group. Unless other health or social problems require delay, we believe the ideal time to complete penile reconstruction in the child is between 6 and 8 months of age. The anesthetic risk is low and, at this age, postoperative care is much easier for the parents than it is when the child is a toddler or toilet trained. In postpubertal patients, the complication rates are significantly higher, which reinforces the concept of performing hypospadias repairs early in life.

Objectives of Repair

The objectives of hypospadias correction are divided into the following categories:

• 1.

  Complete straightening of the penis

• 2.

  Locating the meatus at the tip of the glans

• 3.

  Forming a symmetric, conically shaped glans

• 4.

  Constructing a neourethra uniform in caliber

• 5.

  Completing a satisfactory cosmetic skin coverage

If these objectives can all be attained, the ultimate goal of forming a “normal” penis for the child with hypospadias can be accomplished.

Straightening

Curvature of the penis is difficult to judge, at times, in the preoperative period. Artificial erection, by injecting physiologic saline in the corpora at the time of the operation, allows determination of the exact degree of curvature, which is typically ventrally. This curvature may be caused by ventral skin or subcutaneous tissue tethering, which can be corrected with the release of skin and dartos tissue. Infrequently, the curvature may be secondary to true fibrous tissue. In these cases, it is often required to divide the urethral plate and excise the fibrous tissue down to the tunica albuginea.

Occasionally, even after extensive ventral dissection of chordee tissue, a repeated artificial erection reveals persistent significant ventral curvature. This situation is typically secondary to corporal body disproportion caused by a true deficiency of ventral corporal development. This problem can be corrected by one or a combination of several methods. By dissecting and elevating the urethral plate off the corpora cavernosa, the ventral tunica albuginea can be incised and augmented by inserting either a dermal patch, a piece of small intestinal submucosa, or a tunica vaginalis patch to expand the deficient ventral surface. Elevation of the urethral plate with ventral grafting can result in devascularization of the urethral plate and increases the risk of urethral stricture. This maneuver also prevents the use of grafts due to concern of poor revascularization of the graft and/or graft loss. Alternatively, several nearly full-thickness ventral tunica albuginea incisions (“fairy cuts”) can be made to release the chordee without the need for ventral grafting of the corpora cavernosa. An alternative technique includes excision of the tunica albuginea dorsally with transverse closure to shorten the dorsal surface and straighten the penis. This should be done with caution, as it can lead to damage to the neurovascular bundle that courses dorsally. Other surgeons have had success with multiple tandem dorsal plications without excision of the tunica albuginea, but this can result in significant shortening of the phallus and the straightening may not be long lasting. Anatomic studies suggest that this plication should be done in the midline dorsally to avoid injury to the neurovascular bundle. Still others advocate corporal rotation dorsally with or without penile disassembly to correct the severe chordee. However, this is seldom required given the success with the less invasive techniques mentioned above.

Axial rotation of the penis, or penile torsion, is another aspect of penis straightening that must be managed. This problem can generally be corrected by releasing the dartos layer as far proximal as possible on the penile shaft. Typically, this is done down to the penopubic and penoscrotal junction. This allows the ventral shaft to rotate back to the midline and corrects the torsion. Chordee or torsion can also occur without hypospadias ( Fig. 59.9 ). The management of these boys encompasses the same spectrum of approaches as for those with hypospadias.