Congenital Megalourethra

Congenital megalourethra is a rare anomaly characterized by poor development of penile erectile tissue and severe dilatation of the anterior urethra^1,2. Benacerraf et al, in 1989, were the first to report this condition prenatally². Megalourethra has been increasingly recognized early in the second trimester of pregnancy due to high-definition ultrasound technology and systematic examination of fetal anatomy.

 Q64.9

Congenital megalourethra is a very rare condition. Less than 100 cases have been reported in literature till now in the form of case reports^3-6. It occurs mainly in males, with only one case of female pseudo-hermaphrodite with concomitant penile megalourethra reported to date⁷.

Pathogenesis is not well understood. True megalourethra is characterized by the absence of an anatomic urinary obstruction. Albeit there is a functional obstruction to urine outflow as the urethra “balloons” with fetal voiding, with increasing pressure eventually resulting in efflux of urine. This functional obstruction may also act as a valve like flap mechanism in some cases, producing intermittent mechanical obstruction to the urine stream through the glandular urethra. There are embryogenic assumptions that the condition may behave as a severe case of lower urinary tract obstruction (LUTO), when a transient distal urethral obstruction occurring in early gestation would be responsible for the dilatation of the penile urethra, bladder and upper urinary tract. Another hypothesis of a mesenchymal defect that occurs at 6-10 weeks gestation affecting the genitourinary tract has been postulated^4-6.

The etiology is unknown. It does not seem to be inherited as it occurs sporadically¹. Some gene signaling expression pathways have been described with urogenital anomalies and could be linked to the etiology of megalourethra^8,9.

The main pathologic findings are the agenesis of corpus cavernosum and/or spongiosum without evidence of distal anatomical obstruction. The condition was originally classified as two variants: scaphoid (absence or hypoplasia of the corpus spongiosum with bulging of the ventral urethra), and fusiform (absence or deficiency of both corpora spongiosa and cavernosa with circumferential expansion of the urethra)^3,10. The dilatation of the penile urethra and the urinary stasis in the canal causes a functional obstruction of the lower urinary system that can mimic LUTO. Renal impairment in various degrees can be associated with megalourethra.

This fetal anomaly is not usually associated with chromosomal defects. Associated anomalies, however, are common in both types of megalourethra; more frequently seen with the fusiform type⁵. Common extra-genitourinary findings include^3-5,11-17:

• Gastrointestinal: tracheoesophageal fistula, esophageal atresia, imperforated anus
• Cardiac: ventricular septal defects
• Muscle-skeletal anomalies: limb defects, talipes
• VACTERL association
• Prune-Belly syndrome

The recurrence risk is unknown, but it is generally considered to be low, as the condition occurs sporadically.

Antenatal diagnosis is made by ultrasound, with the presence of one or more features of LUTO: megacystis with or without keyhole bladder sign, renal pelvis dilatation, oligo or anhydramnios, and the unique sonographic features of megalourethra (dilated urethra) and ballooning of the penis. Fetal MRI is a valuable diagnostic tool in cases of suboptimal sonographic imaging, especially in cases of anhydramnios.

Pathology will confirm the absence or hypoplasia of corpus spongiosum and/or cavernosum. Postnatally, enlargement and dilatation of bulgy and lax penis with excess skin, with or without abdominal distension, are noted. In the post natal period, the diagnosis can also be confirmed by a micturating cystourethrogram, which shows a massive dilatation in the anterior urethra.

Any differential of LUTO should be included in the differential diagnosis of megalourethra.

Mimicking conditions could be a cystic abdominal wall mass or an umbilical cord loop or cyst; the latter easily distinguished with colour Doppler. Urethral anomalies mimicking megalourethra like urethral atresia, a web, duplication, or diverticulum should also be considered in the differential diagnosis.

Generally, the keyhole sign suggests LUTO (e.g.: PUV, urethral atresia). However, it is also present in approximately 12% of fetuses with megalourethra^3,4,12,18,19. Therefore, it is imperative to assess the fetal perineum systematically when LUTO is suspected. Screening for renal injury should follow upon megalourethra is diagnosed. Severe oligo/anhydramnios, bilateral hydronephrosis, echogenic kidneys, thick bladder wall are features associated with poor renal function and unfavourable prognosis. A bladder tap is indicated to assess fetal urine biochemistry, predict renal function and postnatal prognosis. Levels of beta-2-microglobulin in fetal urine are the best marker of glomerular filtration (levels >6mg/dL reflect poor renal function)²⁰.

In the first trimester, checking for presence of bladder is part of the systematic early anatomy examination of the fetus. Megacystis is defined as a bladder diameter larger than 7mm at the time of the nuchal translucency scan²¹. More than 90% of cases of megacystis will resolve spontaneously in the second trimester. A detailed anatomy scan and genetic investigation are recommended in cases of persistent megacystis in the second trimester, and it should include detailed imaging of the pelvic floor to confirm normal genitalia morphology. The importance of systematic sonographic evaluation of the fetal perineum as part of the morphology scan is emphasized. Early diagnosis of megalourethra is encouraged to support early clinical management and enable appropriate parental counselling.

The fusiform type is associated with a worse neonatal prognosis, including co-presentation with other anomalies and a mortality rate as high as 60%. In some milder forms of megalourethra spontaneous resolution has been observed in fetuses at 19–34 weeks gestation⁴. Sonographic signs of poor prognosis are:

• Severe oligohydramnios/anhydramnios
• Bilateral hydronephrosis
• Echogenic renal parenchyma
• Early gestational age at diagnosis
• Associated anomalies

Termination of pregnancy may be advised in cases with other severe congenital anomalies and renal impairment.

Management includes genetic counselling (karyotype) and detailed anatomy ultrasound to rule out associated anomalies. If there are sonographic signs of poor prognosis, a bladder tap is indicated to assess renal function and define prognosis. In cases of preserved renal function and anhydramnios, if the couple is committed to the pregnancy, a vesicoamniotic shunt may be an option. At minimum, it will provide normal levels of amniotic fluid essential for lung development. Furthermore, it prevents renal and bladder dysplasia by alleviating the pressure in the urinary system.

There is no specific prevention for megalourethra. However, preconception folic acid supplementation is globally recommended to decrease the risk of genitourinary anomalies.

1. Perrotin F, Ayeva-Derman M, Lardy H, Cloarec S, Lansac J, Body G. Prenatal diagnosis and postnatal outcome of congenital megalourethra: Report of two cases. Fetal Diagn Ther. 2001;16(2):123–8.

2. Benacerraf B, Saltzman D, Mandell J. Sonographic diagnosis of abnormal fetal genitalia. J Ultrasound Med. 1989;8:613–7.

3. Amsalem H, Fitzgerald B, Keating S, Ryan G, Keunen J, Pippi Salle JL, et al. Congenital megalourethra: Prenatal diagnosis and postnatal/autopsy findings in 10 cases. Ultrasound Obstet Gynecol. 2011;37(6):678–83.

4. Moaddab A, Sananes N, Hernandez-Ruano S, Britto ISW, Blumenfeld Y, Stoll F, et al. Prenatal diagnosis and perinatal outcomes of congenital megalourethra: A multicenter cohort study and systematic review of the literature. Vol. 34, Journal of Ultrasound in Medicine. 2015. p. 2057–64.

5. Promsonthi P, Viseshsindh W. Case report and review: prenatal diagnosis of congenital megalourethra. Fetal Diagn Ther. 2010;28(2):123–8.

6. Sepulveda W, Berry S, Romero R, King M, Johnson M, Cotton D. Prenatal diagnosis of congenital megalourethra. J Ultrasound Med. 1993;12:761–6.

7. Di Meglio L, Mazzarelli LL, Boscaino A, Cancemi D, Morelli F, Lonardo MC, et al. Congenital megaurethra in a fetus with Meckel syndrome and in a fetus with female pseudohermaphroditism. The first report of these occurrences. J Prenat Med. 2014;8(3–4):42–426.

8. Podlasek CA, Barnett DH, Clemens JQ, Bak PM, Bushman W. Prostate development requires sonic hedgehog expressed by the urogenital sinus epithelium. Dev Biol. 1999;209(1):28–39.

9. Vaux KK, Jones MC, Benirschke K, Bird LM, Jones KL. Megalourethra: A report of three cases associated with maternal diabetes and a review of the literature - Is sonic hedgehog the common pathway? In: American Journal of Medical Genetics. 2005. p. 314–7.

10. El Akkary EEDES. Megalourethra: Clinical review and management . J Med Res Inst. 2005;26(1):104–7.

11. Krapp M, Geipel A, Germer U, Krokowski M, Gembruch U. First-trimester sonographic diagnosis of distal urethral atresia with megalourethra in VACTERL association. Prenat Diagn. 2002;22:422–4.

12. Wu M, Wu R, Kuo P, Huang K. Prenatal ultrasonographic diagnosis of congenital megalourethra. Prenat Diagn. 1995;15:765–8.

13. Simma B, GaBner I, Brezinka C, Ellemunter H, Krecky A. Complete prenatal urinary tract obstruction caused by congenital megalourethra. J Clin Ultrasound. 1992;20:197–9.

14. Dillon E, Rose P, Scott J. Case report: the antenatal ultrasound diagnosis of megalourethra. Clincal Radiol. 1994;49:354–5.

15. Gandhi S, Cohen M, Sprigg A, Roberts L, Anumba D. Fetal Megalourethra Associated with Hypoplastic left heart and imperforated anus: a previoulsy unreported association. 2008. p. 17:47-51.

16. Ardiet E, Houfflin-Debarge V, Besson R, Subtil D, Puech F. Prenatal diagnosis of congenital megalourethra associated with VACTERL sequence in twin pregnancy: favorable postnatal outcome. Ultrasound Obstet Gynecol. 2003;21:619–20.

17. Fisk N, Dhillon H, Ellis C, Nicolini U, Tannirandorn Y, Rodeck C. Antenatal diagnosis of megalourethra in a fetus with the prune belly syndrome. J Clin Ultrasound. 1990;18:124–8.

18. Duy Anh D, To Nguyen H, Meagher S, Araujo E. Prenatal diagnosis of congenital megalourethra in the second trimester of pregnancy. J Ultrason. 2019;19(79):302–4.

19. Asma B, Jumana B. Megalourethra : a case report managed with a single intrauterine bladder aspiration. AJUM. 2012;15(1):18–23.

20. Muller F, Dommergues M, Bussières L, Lortat-Jacob S, Loirat C, Oury J-F, et al. Development of human renal function : reference intervals for 10 biochemical markers in fetal urine. Clin Chem. 1996;42(11):1855–60.

21. Kenkhuis MJA, Bakker M, Bardi F, Fontanella F, Bakker MK, Fleurke-Rozema JH, et al. Effectiveness of 12–13-week scan for early diagnosis of fetal congenital anomalies in the cell-free DNA era. Ultrasound Obstet Gynecol. 2018;51(4):463–9.

Please note that the maximum upload size is 5MB, and larger images and video clips can be sent to [email protected].