Ursula Kiechl-Kohlendorfer, Theresa Geley, Kathrin Maurer & Ingmar Gaßner
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1 Uterus didelphys with unilateral vaginal atresia: multicystic dysplastic kidney is the precursor of renal agenesis and the key to early diagnosis of this genital anomaly Ursula Kiechl-Kohlendorfer, Theresa Geley, Kathrin Maurer & Ingmar Gaßner Pediatric Radiology ISSN Volume 41 Number 9 Pediatr Radiol (2011) 41: DOI /s z 1 23
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3 Pediatr Radiol (2011) 41: DOI /s z ORIGINAL ARTICLE Uterus didelphys with unilateral vaginal atresia: multicystic dysplastic kidney is the precursor of renal agenesis and the key to early diagnosis of this genital anomaly Ursula Kiechl-Kohlendorfer & Theresa Geley & Kathrin Maurer & Ingmar Gaßner Received: 24 September 2010 / Revised: 11 December 2010 / Accepted: 12 December 2010 / Published online: 30 June 2011 # Springer-Verlag 2011 Abstract Background Uterus didelphys with obstructed hemivagina (UDWOH) and ipsilateral renal agenesis is a distinct but rare entity. Objective To demonstrate the association between UDWOH and a multicystic dysplastic kidney (MCDK) in neonates. To demonstrate the usefulness of sonography with vaginal fluid instillation in the early and reliable diagnosis of this genital anomaly in girls with MCDK. Materials and methods Our patients were five female neonates with a MCDK, which had been detected in utero. We performed sonography of the internal genitalia in all patients before and after filling the vagina with saline. Results In all five girls, sonographic examination revealed uterus didelphys with obstruction of the vagina ipsilateral to the MCDK. In three girls, a dilated ureter originating from the MCDK and extending to the level of the vagina could be clearly demonstrated, with one of these including the ureteric insertion into the atretic vagina. Conclusion MCDK is key to the early diagnosis of UDWOH and will facilitate the provision of appropriate treatment. The neonatal period provides a unique opportunity for detecting uterine anomalies by sonography. An MCDK usually involutes and eventually mimics renal agenesis later in life. U. Kiechl-Kohlendorfer Department of Paediatrics, Division of Neonatology, Neuropaediatrics and Metabolic Diseases, Innsbruck Medical University, Innsbruck, Austria T. Geley : K. Maurer : I. Gaßner (*) Department of Radiology, Paediatric Radiology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria ingmar@gassner.or.at Keywords Female genital abnormality. Uterus didelphys. Renal malformation. Multicystic dysplastic kidney. Neonate. Ultrasonography Introduction The association between uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis was recognised as early as 1922 [1]. Since then, a number of females with this particular anomaly have been reported in the literature [2 8]. It is a rare but well-established entity, sometimes referred to as Herlyn-Werner-Wunderlich syndrome [6, 7]. Almost all studies of patients with uterus didelphys with obstructed hemivagina (UDWOH) have reported coexisting ipsilateral renal agenesis or severe dysplasia [2, 3, 7, 9], whereas only three patients with UDWOH and bilateral normal kidneys have been described [4, 10, 11]. Unilateral occlusion of the duplicated Müllerian system associated with the ipsilateral ectopic ureter inserting into the occluded half of the double vagina has also been reported [5, 8, 9, 12 17]. We have identified only three reports of UDWOH associated with a multicystic dysplastic kidney (MCDK) [8, 18, 19]. We describe five female neonates with UDWOH and MCDK. In all of them, the condition was identified sonographically in the neonatal period. Materials and methods Local research regulations state that institutional review board approval is not mandatory for this type of study, and it was waived for this retrospective imaging review. Between February 1994 and July 2008, five female
4 Pediatr Radiol (2011) 41: Table 1 Ultrasonographic findings and clinical course in five girls with uterus didelphys, unilateral vaginal atresia and ipsilateral multicystic dysplastic kidney. MDCK Multicystic dysplastic kidney Patient Age at presentation (year of presentation) Antenatal ultrasound findings Postnatal ultrasound findings Clinical course 1 1 day (1994) Right renal cyst Right iliac fossa ectopic MCDK, normal left kidney, uterus didelphys with obstructed right vagina 2 1 day (1999) Suspected left MCDK 3 4 days (2005) Left pelvic MCDK, slightly dilated right renal pelvis Left iliac fossa ectopic MCDK, normal right kidney, uterus didelphys with obstructed left vagina, dilated ureter originating from the MCDK extending to the level of the atretic vagina Left pelvic MCDK, normal right kidney, uterus didelphys with obstructed left vagina, slightly dilated left ureter protruding like an ureterocele into the obstructed vagina 4 1 day (2006) Right renal cyst Right orthotopic MCDK, normal left kidney, uterus didelphys with obstructed right vagina, slightly dilated right ureter extending to the level of the obstructed vagina 5 27 days (2008) Suspected right MCDK Right pelvic MCDK, hypertrophic left kidney, uterus didelphys with obstructed right vagina containing echogenic debris within the 1st year. Resection of the vaginal septum at age 13 years Involution of the MCDK within the 1st year within the 1st year within the 1st year within 7 months. Pyocolpos at the age of 10 months, with resection of the septum and drainage of the obstructed right hemivagina neonates, 1 27 days of age, underwent renal and pelvic sonography at the Radiology Unit of the Department of Paediatrics, Innsbruck Medical University, Austria. In three of the girls, MCDK had been suspected in utero. In two of the girls, prenatal ultrasound revealed a renal cystic structure without a definite diagnosis. Pelvic sonography was performed with special attention to potential concomitant genital anomalies. To improve visualisation of the vaginas, saline was instilled via an 8-French feeding tube that had been inserted into the vaginal orifice under sterile conditions and gently advanced. Continuous infusion of the fluid compensated for leakage through the vaginal orifice. The girls were then examined using an Ultramark 8 HDI, HDI 5000 (Advanced Technology Laboratories, Bothell, WA), or Philips iu22 (Philips Healthcare, Bothell, WA) scanner, equipped with a 7- to 4-MHz or 8- to 5-MHz curved array transducer, or a 5- to 12-MHz linear transducer. the girls, transverse pelvic scans revealed two uteri lying side by side, and a cystic structure just below the uterus ipsilateral to the MCDK (Fig. 2). After saline instillation, we visualised the patent vagina, and also identified that the cystic structure represented an obstructed vagina (Fig. 3). In Results The imaging findings and clinical course of all patients are listed in Table 1, and a schematic representation of the pathological anatomy of patients 2 and 4 is presented in Fig. 1. Abdominal sonography in all five neonatal girls showed an MCDK, one in orthotopic and four in caudal ectopic location with a normal contralateral kidney. In all of Fig. 1 Schematic representation of the pathological anatomy of patients 2 and 4
5 1114 Pediatr Radiol (2011) 41: Fig. 2 Patient 2. a Transverse pelvic sonogram shows two uterine fundi: right fundus (white arrowheads), left fundus (black arrowheads). b Transverse scan at lower level shows a left-sided cyst representing an obstructed left vagina (LV). c Longitudinal scan (coronal plane) of the three girls, a moderately dilated ureter originated from the MCDK and extended to the level of the atretic vagina (Figs. 2c, 4). In one of these three, the ureter protruded like a ureterocele into the atretic vagina (Fig. 4). All five were therefore diagnosed as having UDWOH with ipsilateral MCDK. Follow-up until May 2010 showed that the MCDK disappeared almost completely within the 1st year in four of the girls and within the first 2 years in one. In one girls, surgical resection of the septum was necessary at puberty (Case 1). One girl developed pyocolpos at the age of 10 months and needed surgical resection of the septum and drainage of the obstructed vagina (Case 5). Discussion Female genital tract abnormalities are often misdiagnosed during childhood and early adolescence [8]. Malformations left flank demonstrates the multiple anechoic cysts of variable size of a multicystic dysplastic kidney. The dilated ureter (arrows) could be traced to the obstructed ipsilateral left vagina are described as the consequence of an inadequate process of canalisation-fusion-resorption of the Müllerian duct. The frequently described coexistence of reproductive and urinary tract abnormalities suggests an alteration in development affecting both the Wolffian and the Müllerian ducts [9, 20, 21]. Several gene mutations are associated with congenital abnormalities of the kidneys and urinary tract. Hepatocyte nuclearfactor1β (HNF1β) is important in the embryogenesis of the kidneys, pancreas and liver, and is expressed in the Wolffian and the Müllerian ducts [22]. HNF1β gene abnormalities have been reported in individuals with congenital abnormalities of the kidneys and urinary tract [23, 24], suggesting a key role of this transcription factor during development. MCDK is most commonly believed to result from obstruction in the urinary tract during early gestation [25]. There are several clinical reports of a ureter, with or without connection to a hypoplastic kidney, inserting into an Fig. 3 Patient 4. Longitudinal scans obtained after instilling saline into the vagina demonstrate (a) a fluid-filled patent left vagina (LV) with a left uterus (black arrowheads), and (b) an atretic right vagina (RV) with a right uterus (white arrowheads), and an obstructing membrane (arrow). (c) Transverse sonogram shows the atretic right vagina (RV), the patent left vagina (LV) and the obstructing membrane (arrow)
6 Pediatr Radiol (2011) 41: Fig. 4 Case 3. Transverse scan shows the left ureter (black arrowhead) bulging into the atretic left vagina (asterisk); white arrowheads patent right vagina occluded vagina in UDWOH [5, 8, 9, 12, 13, 15 17]. In all of our patients, ultrasound enabled the diagnosis of MCDK and uterus didelphys with obstruction of the ipsilateral vagina. The ureter of the MCDK appeared to be obstructed as a result of insertion into an ipsilateral occluded half of a double vagina. In three of our patients, a dilated ureter could be traced from the MCDK to the obstructed ipsilateral vagina. In one of these, even the ureteric termination in the wall of the blind vagina was clearly visible. To our knowledge, there are only three reports of MCDK with UDWOH; the association with renal agenesis, however, is well-known as Herlyn-Werner-Wunderlich syndrome [8, 18, 19]. The cysts of MCDK may involute over time, in rare cases prenatally, more commonly postnatally, resulting in a small dysplastic, or even absent, kidney, thus mimicking renal agenesis. This phenomenon has been described [18, 26 28] and could also be confirmed in our patients. In addition, the MCDK is frequently located ectopically, which was the case in four of our patients. Small ectopic remnants could easily be overlooked [8]. We therefore speculate that renal agenesis in Herlyn-Werner-Wunderlich syndrome is merely a consequence of MCDK [8] being supported by the fact that routine foetal sonography estimates the incidence of MCDK at 1 in 2,400 live births [29]. In contrast, only a single case of true unilateral agenesis was noted in more than 33,000 foetuses. This incidence is far lower than that quoted for unilateral renal agenesis in adult autopsy series (1 in 1,070) [29]. Therefore, many cases of solitary kidney in the adult population may be the result of involution of MCDK, rather than pure unilateral renal agenesis. Symptoms of UDWOH usually present after menarche with progressive pelvic pain and a palpable mass due to hemihaematocolpos. Menstrual flow from the unobstructed system may be regular despite a dilated obstructed hemivagina. Haematocolpos is suspected only months after menarche, and the diagnosis is made only if this syndrome is suspected; its rarity may contribute to a diagnostic delay [2 4, 6, 8]. Fortunately, renal congenital abnormalities are now usually diagnosed antenatally. Female neonates with MCDK, renal dysplasia or renal agenesis should alert the radiologist to the increased likelihood of associated genital malformation, i.e. UDWOH in girls. Oestrogenic influence increases the overall size of the uterus and the thickness of the myometrium markedly, and increases the definition of the endometrial lining. Uterus didelphys can therefore readily be demonstrated with ultrasound in the neonate and young infant [30]. Fluid instillation into the vagina considerably improves visualisation of the patent and the obstructed vagina [30, 31]. Early and accurate diagnosis of UDWOH is important for correct management at the onset of puberty to prevent acute abdominal pain and dysmenorrhoea. The finding of an MCDK in a girl should prompt further examination to exclude UDWOH. References 1. Purslow CE (1922) A case of unilateral hematocolpos, hematometra, and hematosalpinx (letter). J Obstet Gynecol Br Emp 29: Stassart JP (1992) Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience. Fertil Steril 57: Candiani GB, Fedele L, Candiani M (1997) Double uterus, blind hemivagina and ipsilateral renal agenesis: 36 cases and long-term follow-up. Obstet Gynecol 90: Heinonen PK (2000) Clinical implications of the didelphic uterus: long-term follow-up of 49 cases. Eur J Obstet Gynecol Reprod Biol 91: Zurawin RK, Dietrich JE, Heard MJ et al (2004) Didelphic uterus and obstructed hemivagina with renal agenesis: case report and review of the literature. J Pediatr Adolesc Gynecol 17: Gholoum S (2006) Management and outcome of patients with combined vaginal septum, bifid uterus, and ipsilateral renal agenesis (Herlyn-Werner-Wunderlich syndrome). J Pediatr Surg 41: Orazi C, Lucchetti MC, Schingo PMS et al (2007) Herlyn- Werner-Wunderlich syndrome: uterus didelphys, blind hemivagina and ipsilateral renal agenesis. Sonographic and MR findings in 11 cases. Pediatr Radiol 37: Capito C (2008) Pitfalls in the diagnosis and management of obstructive uterovaginal duplication: a series of 32 cases. Pediatrics 122:e Gilsanz V, Cleveland RH, Reid BS (1982) Duplication of the müllerian ducts and genitourinary malformations. II. Analysis of malformations. Radiology 144: Pinsonneault O, Goldstein DP (1985) Obstructing malformations of the uterus and vagina. Fertil Steril 44: Johnson J, Hillman BJ (1986) Uterine duplication, unilateral imperforate vagina, and normal kidneys. AJR 147: Constantian HM (1966) Ureteral ectopia, hydrocolpos, and uterus didelphys. JAMA 197:54 56
7 1116 Pediatr Radiol (2011) 41: Johansen K (1972) Uterus didelphys with unilateral haematocolpos. J Obstet Gynaecol Br Commonw 79: Burbige KA (1984) Uterus didelphys and vaginal duplication with unilateral obstruction presenting as a newborn abdominal mass. J Urol 132: Shibata T, Nonomura K, Kakizaki H et al (1995) A case of unique communication between blind-ending ectopic ureter and ipsilateral hemi-hematocolpometra in uterus didelphys. J Urol 153: Sheih CP (1997) Ultrasonic detection of a single vaginal ectopic ureter inserted into an imperforate hemivagina. J Clin Ultrasound 25: Wang ZJ (2010) Ectopic ureter associated with uterine didelphys and obstructed hemivagina: preoperative diagnosis by MRI. Pediatr Radiol 40: Prada Arias M, Muguerza Vellibre R, Montero Sanchez M et al (2005) Uterus didelphys with obstructed hemivagina and multicystic dysplastic kidney. Eur J Pediatr Surg 15: Cho Y-A, Lee M-W (2010) Herlyn-Werner-Wunderlich syndrome: imaging findings in 13 cases (abstract). Pediatr Radiol 40: Woolf RB, Allen WM (1953) Concomitant malformations: the frequent, simultaneous occurrence of congenital malformations of the reproductive and urinary tracts. Obstet Gynecol 2: Acien P (1992) Embryological observations on the female genital tract. Hum Reprod 7: Coffinier C, Thépot D, Babinet C et al (1999) Essential role for the homeoprotein vhnf1/hnf1beta in visceral endoderm differentiation. Development 126: Heidet L, Decramer S, Pawtowski A et al (2010) Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol 5: Nakayama M, Nozu K, Goto Y et al (2010) HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 25: Beck AD (1971) The effect of intra-uterine urinary obstruction upon the development of the fetal kidney. J Urol 105: Avni EF (1987) Multicystic dysplastic kidney: natural history from in utero diagnosis and postnatal follow up. J Urol 138: Strife JL (1993) Multicystic dysplastic kidney in children: US follow up. Radiology 186: Keski-Nisula L (1999) Prenatal collapse of cysts in a dysplastic kidney. J Clin Ultrasound 27: Liebeschuetz S, Thomas R (1997) Unilateral multicystic dysplastic kidney. Arch Dis Child 77: Gassner I (2004) Ultrasound of female genital anomalies. Eur Radiol 14:L107 L Kiechl-Kohlendorfer U, Geley TE, Unsinn KM et al (2001) Diagnosing neonatal female genital anomalies using salineenhanced sonography. AJR 177:
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