Basics
Description
Hypospadias is one of the most common congenital anomalies of the male external genitalia. It is characterized by a urethral meatus that opens proximally on the ventral surface of the penis or in the scrotum or perineum instead of at the tip of the glans. Classification is based on the position of the external meatus relative to the penile shaft or surrounding structures (distal, middle, proximal). Although the ventral foreskin is incomplete in the vast majority of cases, the megameatus variant is characterized by an intact foreskin.
Epidemiology
- 1/200-1/300 live male births
- Concordance rates among twins: 18-77%
- Megameatus variant: 5% of cases
- Incidence is likely not increasing over time. Although there have been some data suggesting an increasing incidence over time, the majority of published studies in the U.S. population indicate a stable incidence.
Risk Factors
- In vitro fertilization
- Maternal exposures to substances such as pesticides, hormones, phthalates, and phytoestrogens that can act as endocrine disruptors during penile development
- Associated with maternal preexisting diabetes mellitus, placental insufficiency, and low birth weight
- More common among Caucasians
Genetics
- Likely polygenic
- Familial clustering: 7% of affected boys have an affected 1st- or 2nd-degree relative.
- Equally maternally and paternally transmitted
- Associated with genetic mutations in several genes involved in the androgen pathway and external genitalia development, including homeobox, fibroblast growth factor, and sonic hedgehog genes
Etiology
- Due to incomplete fusion of the urethral folds during penile development, which is an androgen-driven process that occurs during weeks 8-16 of gestation
- Likely multifactorial with environmental and genetic interplay
- Defects in urethral development are usually accompanied by foreskin developmental defects (an incomplete ventral foreskin and dorsal hooded foreskin), except in the megameatus variant
Commonly Associated Conditions
- Usually idiopathic and isolated
- Less commonly associated with some chromosomal abnormalities and ~200 syndromes, including disorders of sexual differentiation (DSD)
- Hypospadias, particularly proximal hypospadias, can be associated with an increased risk of other genitourinary (GU) malformations.
- The most commonly associated GU malformations include the following:
- Chordee
- Cryptorchidism
- Inguinal hernia
Diagnosis
History
- Important to inquire about the following:
- Family history of hypospadias, congenital anomalies, or genetic disorders
- Patient history of genetic disorder and/or DSD
- GU symptoms
- Maternal history of fertility treatments
- Maternal exposures during pregnancy
- Birth history
- For older patients
- Painful erections
- Infertility or difficulties with intercourse
- Difficulty urinating while standing
- Deflected urinary stream
Physical Exam
- Assess for hypospadias in all male newborns with complete GU exam, paying particular attention to the following:
- Any sign of incompletely formed foreskin or dorsal hooded foreskin
- Any phallus curvature
- Location of the meatus
- Presence of rugated scrotum
- Impalpable testes
Diagnostic Tests & Interpretation
Lab
- No tests are needed for isolated hypospadias.
- If testes are impalpable bilaterally with proximal hypospadias, consider workup for DSD.
- Additional workup for DSD as needed based on level of concern
Imaging
- Not usually indicated
- Renal ultrasound or voiding cystourethrogram in cases of proximal hypospadias
- Ultrasound of urinary tract and internal genitalia if hypospadias is present in conjunction with cryptorchidism or nonpalpable testicle(s)
Differential Diagnosis
DSD such as congenital adrenal hyperplasia or partial androgen insensitivity syndrome
Treatment
General Measures
- Preferably refer to pediatric urologist within the first few weeks of life.
- Preoperative stimulation with parenteral testosterone may be required to increase penis size in cases of micropenis to improve surgical outcomes.
- Cases of mild, distal hypospadias may be observed.
Alert
- For newborn circumcision, retract the foreskin (megameatus variant requires foreskin retraction for detection). If any abnormalities noted, abort the circumcision and refer to a pediatric urologist.
- In cases of hypospadias, circumcision is absolutely contraindicated because foreskin is used in hypospadias repair.
- Bilateral impalpable testes and hypospadias during newborn period must be worked-up to rule out DSD.
Surgery/Other Procedures
- Surgical repair
- Outpatient procedure
- May be accompanied by chordee repair if needed
- Performed at age 6 months-1 year to minimize psychological trauma of surgery
- Complex cases may require staged repair, with stage 1 generally performed at 6 months of age and stage 2 at 1 year of age.
- Perioperative care may include the following:
- Antibiotics (no standard course duration)
- Pain management (generally with a caudal nerve block and acetaminophen with opioid analgesic or ketorolac as needed)
- Type of repair performed is based on patient's anatomy.
- Some types of repair may involve temporary urethral stent placement.
- Types of repair include the following:
- Urethromeatoplasty
- Meatal advancement and glanuloplasty (MAGPI)
- Meatal inverted V flap
- Sleeve technique
- Flip-flap technique (local flap)
- Adjacent tissue transfer
- Glans approximation procedure
- Thiersch-Duplay
- Transverse incised plate or Snodgrass procedure
- Most common complications include the following:
- Urethrocutaneous fistula
- Urethral diverticulum
- Urethral or meatal stenosis
- Dehiscence
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Surgical dressings are variable and surgeon dependent.
- Postoperative clinic visit (surgeon-dependent)
- If urethral stent is placed, removal usually occurs on postoperative days 5-14 at clinic visit.
- Antibiotics may be continued postoperatively.
Prognosis
Success rate is generally high, although dependent on the type of repair, degree of hypospadias, and patient's overall medical condition.
Additional Reading
- Kalfa N, Liu B, Klein O, et al. Mutations of CXorf6 are associated with a range of severities of hypospadias. Eur J Endocrinol. 2008;159(4):453-458. [View Abstract]
- Kalfa N, Liu B, Klein O, et al. Genomic variants of ATF3 in patients with hypospadias. J Urol. 2008;180(5):2183-2188; discussion 2188. [View Abstract]
- Kalfa N, Philibert P, Baskin LS, et al. Hypospadias: interactions between environment and genetics. Mol Cell Endocrinol. 2011;335(2):89-95. [View Abstract]
- Madhok N, Scharbach K, Shahid-Saless S. Hypospadias. Pediatr Rev. 2009;30(6):235-237. [View Abstract]
- Moriyama M, Senga Y, Satomi Y. Klinefelter's syndrome with hypospadias and bilateral cryptorchidism. Urol Int. 1988;43(5):313-314. [View Abstract]
- van der Zanden LF, van Rooij IA, Feitz WF, et al. Aetiology of hypospadias: a systematic review of genes and environment. Hum Reprod Update. 2012;18(3):260-283. [View Abstract]
- Wang MH, Baskin LS. Endocrine disruptors, genital development, and hypospadias. J Androl. 2008;29(5):499-505. [View Abstract]
- White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21(3):245-291.
- Zaontz M, Long CJ. Management of distal hypospadias. AUA Update Series. 2013;32(Lesson 5):1-51.
Codes
ICD09
ICD10
- Q54.9 Hypospadias, unspecified
- Q54.1 Hypospadias, penile
- Q54.3 Hypospadias, perineal
- Q54.2 Hypospadias, penoscrotal
- Q54.8 Other hypospadias
SNOMED
- 416010008 hypospadias (disorder)
- 204888000 hypospadias, penile (disorder)
- 702462000 Scrotal hypospadias (disorder)
- 204890004 Hypospadias, perineal (disorder)
- 204889008 Hypospadias, penoscrotal (disorder)
FAQ
- Q: Does the patient with hypospadias routinely have other urinary tract abnormalities?
- A: No. Hypospadias is usually an isolated anomaly, and most patients have no other anatomic problems.
- Q: Should a newborn circumcision be performed if there are concerns with the meatal opening?
- A: Circumcision should be delayed, and the patient should be evaluated by a pediatric urologist.
- Q: Are there any medical alternatives to surgical repair?
- A: No. Surgery is the only treatment of hypospadias, but very mild cases may not warrant surgical repair.