Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 137

Lower Urinary Tract Anomalies of 7 Urogenital Sinus and Female Genital Anomalies

Theresa E. Geley and Ingmar Gaßner

CONTENTS 7.1 Introduction

7.1 Introduction 137 Congenital anomalies of the female genital tract result from müllerian duct anomalies and/or abnor- 7.2 Embryology of the Female Genitalia 138 malities of the urogenital sinus or cloaca. Failure of 7.3 Müllerian Duct Anomalies 139 fusion of the müllerian ducts results in a wide vari- 7.3.1 Müllerian Agenesis 141 ety of fusion abnormalities of the uterus, cervix, and 7.3.2 Disorders of Vertical Fusion 142 vagina (Gruenwald 1941). Müllerian duct abnor- 7.3.3 Disorders of Lateral Fusion 142 malities may occur alone or in association with uro- 7.3.4 Vaginal Anomalies With or Without Obstruction 143 genital sinus or cloacal malformations. Persistence 7.3.5 Diagnostic Imaging of Müllerian Duct of the cloaca is believed to be caused by an abnormal Anomalies 146 development of the dorsal part of the cloaca and the urorectal septum (Stephens 1983b; Nievelstein 7.4 Ovarian Cysts 150 7.4.1 Diagnostic Imaging of Ovarian Cysts 151 et al. 1998). Urogenital sinus malformations occur after the cloaca has been organized into the urogeni- 7.5 Lower Urinary Tract Anomalies of tal sinus and the anus (Williams and Bloomberg Urogenital Sinus 152 1976). Early and complete assessment of the patients, 7.5.1 Female Hypospadias 153 including radiological and biochemical examina- 7.5.1.1 Diagnostic Imaging of Female Hypospadias 153 tions, is mandatory to provide an optimal basis for 7.5.2 Urogenital Sinus in Disorders of treatment that will have a great inﬂ uence on the Sex Development 153 quality of the patient’s later life. Due to the close 7.5.2.1 46, XX Disorders of Sex Development 154 embryologic relationship between the urinary and 7.5.2.2 46, XY Disorder of Sex Development 154 7.5.2.3 Ovotesticular Disorder of the genital tract, malformations involving both Sex Development 156 organ systems are very common. Understanding 7.5.2.4 Diagnostic Imaging of Urogenital Sinus the development of the urogenital system is neces- Anomalies 156 sary to comprehend the full spectrum of congenital 7.5.3 Cloacal Malformation 157 anomalies of the female genitalia. 7.5.3.1 Diagnostic Imaging of Cloacal Malformation 160 Ovarian cysts are frequently seen during prenatal and postnatal pelvic ultrasound and have, therefore, References 161 been included in this chapter, although they are not closely related etiologically to the above-mentioned malformations and organ systems.

T. E. Geley, MD I. Gaßner, MD Section of Pediatric Radiology, University of Innsbruck, Section of Pediatric Radiology, University of Innsbruck, Medical School, Anichstrasse 35, 6020 Innsbruck, Austria Medical School, Anichstrasse 35, 6020 Innsbruck, Austria

FOT2.indb 137 21.01.2008 14:06:07 138 T. E. Geley and I. Gaßner

external and internal male genitalia as well as for the 7.2 suppression of further development of the müllerian Embryology of the Female Genitalia duct into female genital structures. In the absence of a Y chromosome, zygotes with two or more X chro- Sex determination at the chromosome level is related mosomes will develop ovaries and female internal to the presence or absence of a Y chromosome. and external genitalia. Whereas the X chromo- Those individuals with a Y chromosome (including some is essential for development, zygotes lacking XXY, XXXY, etc.) will develop into males, and those a Y chromosome (45X) are viable, but are unable without one will become females. Some individu- to develop differentiated gonads (streak gonads) als, however, will undergo what is referred to as 46, (Aaronson 1992; Wilson and Goldstein 1975). XX testicular disorder of sex development (DSD) Both the internal and the external genital organs or 46, XY complete gonadal dysgenesis, also called develop in coordination with the urinary and ano- primary sex reversal, whereby the X and Y chro- rectal system at an early stage of gestation (Fig. 7.1). mosomes cross over and exchange the sex deter- The internal genital organs as well as the lower uri- mination SRY gene (Hughes et al. 2006; Koopman nary system originate from two paired urogenital 1995; Marrakchi et al. 2005). This relatively rare structures that develop in both sexes: the meso- occurrence (approximately 1 in 20,000 births) can nephric ducts (wolfﬁ an ducts) and the parameso- lead to males with two X chromosomes and females nephric ducts (müllerian ducts) (Moore 1993). At with a Y chromosome. While gonad development is 5 weeks of gestation the ureteral bud arises from the a result of the presence or absence of the sex deter- distal segment of the wolfﬁ an duct to grow dorsally mination gene, sex differentiation is determined by and soon becomes connected with the primordium the hormonal products of the gonads including the of the permanent kidney or metanephric blastema. müllerian-inhibiting substance (MIS) produced by The ureteral bud forms the ureter, the renal pelvis, sertoli cells. calyces, and the intrarenal collecting ducts and acts The two factors produced by the testes, andro- as an inducer of differentiation of the renal blas- gen, and MIS, are essential for the formation of the tema into the adult kidney. Between the 6th and the

Fig. 7.1a–d. Schematic presentation of the embryology of the female genitourinary tract. a The mesonephric ducts a b (wolfﬁ an ducts) connect the mesonephros to the cloaca. b At approximately 5 weeks of gestation the ureteric bud originates from the wolfﬁ an duct, reaches the metanephros and induces its differentiation into the kidney while the mesonephros degenerates. The mül- lerian ducts fuse at about 7–9 weeks in the midline to form the uterovaginal canal. c At 8 weeks the uterovaginal canal reaches the urogenital sinus at the müllerian tubercle. The urogenital sinus results from the separation of the cloaca into urogenital sinus and rectum. d The vagina becomes patent at approximately 22 weeks. The wolff- ian ducts are resorbed and remnants cdare referred to as Gartner’s duct

FOT2.indb 138 21.01.2008 14:06:07 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 139

8th week the segment of the wolffi an duct distal to Between the 4th and 6th weeks, the complex pro- the origin of the ureteral bud dilates and is incorpo- cess of partitioning the internal and the external rated into the wall of the vesicourethral canal. The cloaca into separate urinary and anorectal systems ureter undergoes a craniolateral shift relative to the takes place. The theories formulated by Rathke wolffi an duct to open into the bladder. With further (1882), Retterer (1890), and Tourneux (1888) growth of the surrounding structures, the ureteral dominated the understanding of the development opening migrates to the lateral corners of the blad- of the cloaca for decades. More recently, however, a der trigone, while the wolffi an ducts descend with new model of cloacal development has been put for- the urogenital sinus. In the female, the wolffi an duct ward by Van der Putte (1986), Hartwig (1992), epithelium forms the posterior wall of the entire and Kluth et al. (1995). According to their theory, urethra (Stephens 1983a). the distance between the caudal tip of the urorec- During the 6th week of gestation the mülle- tal septum and the cloacal membrane decreases due rian ducts develop alongside the wolffi an ducts to the unfolding process of the embryo and does ( Gruenwald 1941). The müllerian ducts are divided not involve an active proliferation process of the into two segments demarcated by the insertion of the urogenital septum as suggested earlier. According ligamentum inguinale, which eventually becomes the to this model, the urorectal septum is formed by round ligament. The distal segments of the müllerian fusion of the surrounding extraembryonic meso- ducts move towards the midline and soon fuse into a derm of the yolk sac and allantois. The tip of this single tube, the uterovaginal canal. The septum that septum marks the cranial border of the cloaca and divides the uterovaginal canal disappears at 11 weeks. subdivides the internal cloaca into the urogeni- The uterovaginal canal elongates to join the urogenital sinus and the anorectal canal. However, fusion tal sinus at the müllerian tubercle between the two between the cloacal membrane and the urorectal openings of the wolffi an ducts. Further differentia- septum, as suggested by the previous theories, never tion and canalization result in the formation of the occurs (Nievelstein et al. 1998). The cloacal mem- uterus and the cervix. At 12 weeks the vagina forms. brane eventually ruptures to allow communication Induced by the fusion of the uterovaginal canal with between the internal and the external cloaca. the urogenital sinus, bilateral endodermal evagina- The process of partitioning then spreads cau- tions, the sinovaginal bulbs, form in the area of the dally into the external cloaca. The perineal mound müllerian tubercle (Moore 1993). The sinovaginal (i.e., the tip of the urorectal septum) separates the bulbs proliferate into the primitive vaginal plate. urogenital sinus from the anus. The inner genital Canalization of this plate starts at the urogenital folds proliferate to form the perineum and the labia sinus forming the vaginal epithelium and the entire minora, whereas the outer genital folds develop into wall of the distal third of the vagina. The nonepithe- the labia majora. lial components of the proximal two-thirds of the vagina, however, are of uterovaginal canal origin. The proximal segments of the müllerian ducts remain un-united to form the fallopian tubes. In females the wolffi an duct is fi nally resorbed, leav- 7.3 ing only scattered remnants forming an interrupted Müllerian Duct Anomalies channel alongside the fallopian tubes, the proximal uterus, within the cervix and the anterolateral wall Based on the embryological development of the of the vagina, ending at or just above the level of female genital system, uterovaginal malformations the hymen. These remnants are then referred to as are classifi ed as müllerian agenesis in cases of a Gartner’s duct. developmental defect of the caudal portion of the Development of the external genital organs, the müllerian ducts (Mayer-Rokitansky-Küster-Hauser urethra, and the anus involve transformation pro- syndrome), disorders of lateral fusion resulting from cesses of the internal and external cloaca, which are failure of the two müllerian ducts to fuse, and disor- separated by the cloacal membrane in a transverse ders of vertical fusion that are caused by faults in the plane (Stephens 1983a; Nievelstein et al. 1998). union between the müllerian tubercle and deriva- At 4 weeks the internal cloaca is a single chamber, tives of the urogenital sinus (transverse vaginal into which issue the large intestine, the hindgut, the septum, cervical agenesis, disorders of the hymen). allantois, and the wolffi an ducts. Disorders of lateral fusion are very heterogeneous,

FOT2.indb 139 21.01.2008 14:06:08 140 T. E. Geley and I. Gaßner

but are best classifi ed according to Buttram and Gibbons who proposed a classifi cation of müllerian anomalies in 1979, which is now the guideline of the American Fertility Society. According to this classifi cation, müllerian duct anomalies are classifi ed into six groups. A particular patient, however, a d may not necessarily fi t neatly into a single category. Class I–class V are shown in Figures 7.2–7.4; class VI (not shown) refers to a uterus with luminal changes secondary to in utero exposure to diethylstilbestrol

b e

a c c f

Fig. 7.4a–f. Schematic presentation of classes III, IV, and V. a Uterus didelphys (class III); b–d bicornuate uterus (class IV): b complete, c partial, d arcuate; e,f septate uterus (class V): e complete, f partial d (DES), used to prevent miscarriage between the late b 1940s and the 1970s. Fig. 7.2a–d. Schematic presentation of class I: Müllerian Due to the frequent association of vertical and agenesis or hypoplasia. a Vaginal. b Combined vaginal and lateral fusion disorders, vaginal anomalies are best fundal. c Cervical. d Fundal considered according to the presence or absence of an obstruction. Syndromes reported to be associated with genital anomalies in the female encompass Mayer-Rokitan- sky-Küster-Hauser syndrome (müllerian agenesis), MURCS association (müllerian duct aplasia, renal agenesis/ectopia, cervical somite dysplasia), hand- foot-genital syndrome (bifi d uterus, double uterus, acseptate vagina), VATER, VACTEL, VACTERL, VACTER association (vertebral, vascular, and anal anomalies, auricular defects, cardiovascular anomalies, tracheoesophageal fi stula, esophageal atresia, renal anomalies, radial defects, rib and limb anomalies), Beckwith-Wiedemann syndrome (bicornuate uterus), EEC syndrome (transverse vaginal septum), Fraser syndrome (bicornuate uterus, vaginal atre- b d sia, rudimentary uterus), Roberts syndrome (septate vagina), renal-genital-ear anomalies (vaginal atre- Fig. 7.3a–d. Schematic presentation of class II: unicornuate sia), Schinzel-Giedion syndrome (hymenal atresia), uterus. a With a rudimentary, communicating horn. b The Taybi rudimentary horn has no cavity, no endometrium. c The Jarcho-Levin syndrome (uterus didelphys) ( rudimentary horn is noncommunicating with active endo- and Lachman 1996), and fi nally Pallister-Hall syn- metrium. d No rudimentary horn drome (vaginal atresia) (Unsinn et al. 1995).

FOT2.indb 140 21.01.2008 14:06:08 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 141

7.3.1 It affects 1 in 4,000–5,000 otherwise normal (46 XX) Müllerian Agenesis girls. Mayer-Rokitansky-Küster-Hauser syndrome type A (typical form) shows normal- appearing Mayer-Rokitansky-Küster-Hauser syndrome is external genitalia, absence of the vagina and uterus, characterized by the absence of the entire vagina normal fallopian tubes, normal ovaries, and no renal or, more commonly, the proximal two-thirds of the anomalies. In type B (atypical form), the uterus may vagina; absence or abnormalities of the uterus; and be normal except for the lack of a conduit to the malformations of the upper urinary tract (Fig. 7.5). introitus or may be rudimentary, commonly show-

a b

c d

Fig. 7.5a–d. Mayer-Rokitansky-Küster-Hauser-syndrome in a 10-year-old girl with normal external genitalia and normal female karyotype. a Longitudinal, b transverse pelvic sonograms: between the ﬂ uid-ﬁ lled rectum (R) and the bladder (B), neither vagina nor uterus is visualized. c Transverse scan through the right iliac fossa: Normal ovary (arrows) with follicles. Iliac vessels (asterisks). d Schematic representation of genital anomalies encountered in Mayer-Rokitansky-Küster-Hauser syndrome. The rudimentary uterine horn consists of muscle bundles and some endometrial tissue. The tubes and ovaries are normally displayed. The perineal anatomy shows a female phenotype, but no vaginal opening

FOT2.indb 141 21.01.2008 14:06:09 142 T. E. Geley and I. Gaßner

ing disorders of the lateral fusion with aplasia of 7.3.2 one or both uterine horns, or asymmetry of the Disorders of Vertical Fusion horns if both are present. However, any of the lateral or vertical fusion abnormalities with or without The disorders of the vertical fusion of the müllerian obstruction may be seen. The fallopian tubes are ducts consists of transverse vaginal septa, imperfo- abnormally developed (hypoplasia and aplasia of rate cervix, and cervical agenesis and results from one or both tubes) and ovarian anomalies such as faults in the junction between the descending mül- inguinal hernia containing an ovary, no descent of lerian ducts and the ascending urogenital sinus. In the ovary, absence of the ovary, or streak ovaries transverse septa the interruption may be complete or have been reported (Taybi and Lachman 1996; incomplete and occur at any level of the vagina, some- Bazi et al. 2006). times at multiple levels. The vagina is obliterated by Malformations of the upper urinary tract occur fi brous connective tissue with vascular and muscular in up to 50% (Rosenberg et al. 1986) of all affected elements lined by squamous epithelium. The septum females and include renal hydronephrosis, agenesis, may be a thin membrane, but more commonly fusion, dysplasia, and unilateral ectopia. Associated involves a whole segment of the vagina (segmental anomalies of the ureters such as ectopia and vesi- vaginal atresia). An increased incidence of associated coureteral refl ux have also been reported. Skeletal proximal müllerian duct anomalies is found, such as anomalies are seen in approximately 10% (Taybi and lateral fusion abnormalities of the uterus, stenosis, Lachman 1996) of patients who have malformations hypoplasia, or absence of the uterus and the fallopian of the spine, such as wedge vertebrae, fusions, rudi- tubes (Silverman and Kuhn 1993). mentary vertebral bodies, and supernumerary ver- Although of different embryological origin, the tebrae. Absence or underdevelopment of one lower imperforate hymen is commonly listed together sacral segment and coccyx as well as tethered spinal with defects of the vertical fusion of the müllerian cord have been reported. Other skeletal anomalies ducts. The hymen membrane separates the vaginal include syndactyly, absence of a digit, long proximal lumen from the urogenital sinus and is entirely of phalanx of digits 3 and 4, long metacarpals of digits urogenital sinus origin. The hymen membrane usu- 1–4, carpal abnormalities, hypoplasia of the thenar ally ruptures in the perinatal period and remains eminence, and bilateral femoral hypoplasia. as a thin fold around the vaginal orifi ce. As with The typical patient seeks medical advice at the all vaginal obstructions found in association with expected time of onset of puberty because of pri- a normal uterus, imperforate hymen may either be mary amenorrhea. Upon physical examination the symptomatic in the newborn period or after onset external genitalia are those of a normal female, of puberty due to the development of hydrocol- although the introitus may end in a shallow blind pos/hydrometrocolpos or hematocolpos/hemato- pouch. Depending on whether there is a functional metrocolpos, respectively. A protruding interlabial endometrium, cyclic or intermittent abdominal pain mass in association with a midline pelvic mass is may be present due to hematocolpos or hematome- found upon physical examination. Imperforate trocolpos. Mayer-Rokitansky-Küster-Hauser syn- hymen is the simplest and most easily correctable drome is the second most frequent cause of primary of all vaginal obliterations. It is not associated with amenorrhea after the classic Turner syndrome. an increased incidence of müllerian duct or renal The classic Turner syndrome (55% of 45 X0 anomalies (Silverman and Kuhn 1993). patients) shows ovarian dysgenesis, primary amenorrhea, and infantile uterus, vagina, and breasts. Less commonly, a mosaicism (X/XX, X/XY, X/XX/ 7.3.3 XY), isochromosome X, ring X, or partial deletion of Disorders of Lateral Fusion the X chromosome is found. In chromosomal mosaic patients the whole spectrum from absent to infantile Incomplete fusion of the distal segments of the two to normal-sized ovaries, uterus, and vagina can be müllerian ducts results in various degrees of bifi dity seen, explaining why 5% of all Turner syndrome of the uterus and/or vagina (Jarcho 1946) (Fig. 7.6). patients have spontaneous menstruation. Patients Disorders of the lateral fusion are rare in the general carrying a Y chromosome in their karyotype have a population and, in the absence of obstruction, are higher risk for developing gonadoblastoma (Siegel asymptomatic during childhood or at puberty. How- 1995). ever, these anomalies are more frequently encoun-

FOT2.indb 142 21.01.2008 14:06:11 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 143

Fig. 7.6a–c. Uterus didelphys with double vagina in a 16-year-old girl. a Filling of the vagina with plain sodium solution. Transverse sonogram shows two uteri (closed arrowheads) with thickened, echogenic endometrium (asterisks) and two fl uid-fi lled vaginas (V) behind the empty bladder. b With a slightly oblique transducer position no sonographic dropout occurs and allows clear demonstration of the two separate vaginas (V). B, Bladder. c Contrast fi lling of the vagina. Anterior posterior view of the double vagina b after retrograde fi lling. The septum is clearly visible

tered in infertile women. This group of uterine mal- vaginal anomalies according to the presence or the formations includes septate, bicornuate, didelphic, absence of obstruction (Fig. 7.7). Nonobstructive and unicornuate uterus (Figs. 7.2–7.4) (Buttram vaginal anomalies encompass biﬁ d vagina, longi- and Gibbons 1979). A minor and relatively common tudinal vaginal septum, and incomplete transverse form of fusion defects of the müllerian ducts is septum. Among the obstructive vaginal anomalies simple septate vagina, in which the vagina is divided are imperforate hymen, complete transverse vaginal in two lateral compartments by a midline sagittal septum, and atresia of the uterine cervix and vagina, septum without uterine anomalies. as mentioned above, as well as unilateral obstructive vaginal septum and obstruction of a unilateral rudimentary horn. 7.3.4 Vaginal Anomalies With or Without Obstruction Unilateral obstructive vaginal septum. In some cases of duplicated uterus with a midline vaginal septum Because of the frequent association of vertical with the caudal end of one hemivagina, more often the lateral fusion anomalies, it is useful to consider left, is obstructed (uterus didelphys with septate

FOT2.indb 143 21.01.2008 14:06:11 144 T. E. Geley and I. Gaßner

and hydronephrosis) due to the close developmental association between the genital system (originating from the müllerian ducts) and the urinary system (originating from the wolfﬁ an ducts) (Silverman and Kuhn 1993). a e Obstruction of a unilateral rudimentary horn. This condition is found at the extreme end of the spectrum of müllerian duct anomalies (Fig. 7.3). One of the two müllerian ducts fails to develop or is par- tially or completely (unicornuate uterus) resorbed. The ipsilateral fallopian tube is, therefore, absent or rudimentary, whereas both ovaries are present and b f functional. If a rudimentary hemiuterus contains functioning endometrium, the patient may develop an accumulation of mucus within this structure, during the neonatal period, or blood, at the time of puberty. Renal agenesis or severe renal dysplasia on the side of the missing or malformed hemiuterus is the rule (Gilsanz et al. 1982; Woolf and Allen c g 1953).

Conclusion Due to the close developmental relationship of the urinary and the genital tract, malformations frequently occur in both of these systems. Major renal anomalies are common in patients present- d h ing with unilateral obstruction or agenesis of duplicated structures derived from the müllerian Fig. 7.7a–h. Schematic presentation of vaginal anomalies with and without obstruction. a Imperforate hymen. b In- duct. complete transverse vaginal septum. c Longitudinal vaginal septum, uterus didelphys. d Bifi d vagina, uterus didelphys. e Obstruction of a hemivagina, hematometrocolpos, uterus didelphys. f Imperforate hymen, hematocolpos; a protruding vestibular mass is found. g Partial vaginal agenesis, hematometrocolpos. h Transverse vaginal septum, hematometrocolpos, spilling of menstrual blood via the fallopian tubes Fig. 7.8a–g. Uterus didelphys with left multicystic dysplastic kidney (MCDK) and ipsilateral vaginal obstruction. a Longitudinal scan (coronal plane) of the left fl ank. MCDK: vagina and uterovaginal obstruction) (Fig. 7.8). No multiple anechoic cysts of variable size and shape that do not hymen tissue is found on the obstructed side. The communicate with each other. The dilated ureter (arrows) disorder may present at birth with a pelvic mass could be traced from the MCDK to the obstructed ipsilateral left vagina. b Transverse pelvic sonogram shows two due to accumulated genital secretion. The ipsilat- uterine fundi: right fundus (closed arrowheads), left fundus eral fallopian tube may also be enlarged. More com- (open arrowheads). c Transverse scan at lower level than b monly, however, the patient presents at puberty with shows a left-sided cyst representing obstructed left vagina a pelvic mass and cyclic abdominal pain despite a (LV). d,e Longitudinal sonograms obtained after instilling normal menstrual blood fl ow. The obstructed vagi- saline solution in vagina demonstrated fl uid-fi lled patent nal compartment may protrude as a cystic mass right vagina (RV) with right uterus (arrowheads); e atretic left vagina (LV) with left uterus (arrowheads). Obstruct- from the introitus. An obstructed hemivagina and ing membrane (arrow). f Transverse scan shows the atretic double uterus are almost always associated with left ureter (closed arrowheads) bulging into the atretic left severe ipsilateral renal anomalies (renal agenesis, vagina (asterisk). Functional right vagina (open arrow- renal dysplasia, ectopia, ipsilateral ectopic ureter, heads). g Schematic representation

FOT2.indb 144 21.01.2008 14:06:12 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 145

f g

FOT2.indb 145 21.01.2008 14:06:13 146 T. E. Geley and I. Gaßner

7.3.5 abdominal pain after the onset of puberty are the Diagnostic Imaging of most common reasons for consultation. Müllerian Duct Anomalies Ultrasound is the most common ﬁ rst-step imaging technique in the evaluation of patients of both Pediatric radiologists will commonly come across age groups. Subsequent tests such as MR imaging müllerian duct anomalies at two different stages of and ﬂ uoroscopic studies provide additional infor- a girl’s life. In neonates diagnostic requests encom- mation (Fielding 1996; Wagner and Woodward pass evaluation of a palpable abdominal mass and 1994). In particular, patients with müllerian agen- delineation of associated genital malformation in esis may need MR imaging to clearly document their urogenital sinus anomalies. In adolescent girls delay ovaries and the rudimentary uterus (Rosenberg et in puberty or primary amenorrhea as well as pelvic al. 1986; Rosenblatt et al. 1991; Lang et al. 1999).

a b

c d

Fig. 7.9a–d. Normal neonatal uterus. a–c Longitudinal sonograms: the cervix and fundus are clearly discernible. The cervix (open arrowheads) has a greater diameter and length than fundus (closed arrowheads). There is a small amount of ﬂ uid within the endometrial canal at the junction of fundus and cervix (asterisk). Single nabothian cyst in the cervix (closed arrow). The inner layer of myometrium is hypoechoic (subendometrial halo). Echogenic endometrial glands (open arrows). In the ﬂ uid-distended vagina cervical mucus adherent to the vaginal part of cervix is visible (M). d Transverse scan at the level of the fundus shows the uterine horns (area where the tubes enter the uterus; curved arrows)

FOT2.indb 146 21.01.2008 14:06:15 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 147

Due to the high association of müllerian duct Estrogen stimulation at the onset of puberty results anomalies with anomalies of the urinary tract, in fundal swelling and endometrial echo (Fig. 7.11). every patient diagnosed with genital malforma- The postpubertal uterus has the adult pear-shaped tions, whether newborn or adolescent, needs a care- appearance and measures 5–8u1.5u3 cm (Teele and ful investigation of the urinary tract. Renal ultra- Share 1992; Ziereisen et al. 2005) (Fig. 7.11). sound and voiding cystourethrography should be performed on all patients diagnosed with a dupli- Sonographic features of hydro/hematocolpos and cated uterine system. Pelvic sonography, on the hydrometro-/hematometrocolpos. Sonographic eval- other hand, is mandatory in patients with unilateral uation of a newborn or adolescent girl with a pal- renal agenesis, ectopia, multicystic dysplastic, or pable abdominal mass may reveal a midline cystic horseshoe kidney (Gilsanz et al. 1982; Woolf 1953; mass refl ecting congenital hydrocolpos or hydrome- Gilsanz and Cleveland 1982). In cases of mül- trocolpos in the former and hematocolpos or hema- lerian agenesis spinal ultrasound in newborns and tometrocolpos in the latter (Figs. 7.12, 7.13). MR imaging in older girls as well as plain X-rays are In some cases the cystic dilatation of the vagina required to rule out spinal cord anomalies and skel- may be very impressive with the less easily dis- etal anomalies, respectively. tensible uterus attached to it as a small cap-like structure. The fl uid-fi lled vagina and/or uterus Sonographic features of the uterus in neonate, pre- may be seen as a cystic structure homogeneously pubertal, and pubertal girls. Under the infl uence and completely fi lled appearing as a solid mass, or of maternal and placental hormones the neonatal cystic with scattered internal echoes, or completely uterus is more prominent and measures 3.5 cm in anechoic. A fl uid-debris level might be found and is length and 1.4 cm in thickness, with a defi nable a crucial fi nding in congenital hydrocolpos/hydro- endometrial stripe (Fig. 7.9). metrocolpos that differentiates the vagina from An uterus didelphys or bicornuate uterus can, the bladder (Blask et al. 1991a,b). Association of therefore, readily be demonstrated. The prepubertal hydro/hematocolpos and hydrometro/hematome- uterus is smaller, has a tube shape, and a non-appar- trocolpos with an obliterate introitus or a shallow ent endometrium, making it almost impossible to blindly ending vaginal pouch is strongly sugges- evaluate uterine anomalies (Fig. 7.10). tive of müllerian agenesis or transverse vaginal septum, but has to be distinguished from pelvic masses caused by an imperforate hymen or unilateral occlusion of a duplicated vagina (Blask et al. 1991b).

Fig. 7.11. Normal postmenarchal uterus of a 12-year-old girl. Fig. 7.10. Normal prepubertal uterus of a 4-year-old Longitudinal sonogram: pear-shaped uterus. Diameter and girl. The uterus is small with a fundus to cervix ratio of length of the fundus (closed arrowheads) are greater than 1:1. B bladder, R rectum those of the cervix (open arrowheads)

FOT2.indb 147 21.01.2008 14:06:17 148 T. E. Geley and I. Gaßner

a b Fig. 7.12a,b. Imperforate hymen with moderate hydrocolpos. a The imperforate hymen protrudes between the labia. b Translabial sagittal scan: the vagina (V) is moderately dilated and the ﬂ uid protrudes the hymen (arrowheads) spherically

a b

Fig. 7.13a–c. Imperforate hymen with excessive hydrocolpos. a,b Longitudinal scans: the low-level echoes within the markedly dilated vagina (V) represent mucous secretions. a The uterus with cervix (open arrowheads) projects into the dilated vagina (V). Mucus plug (closed arrowhead) adherent to the cervical ostium. b The hydrocolpos (V) compresses the inferior vena cava (arrows). c Transverse pelvic scan: the ureters (U) are c dilated due to distal ureteral compression. V; hydrocolpos

FOT2.indb 148 21.01.2008 14:06:17 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 149

In addition, fl uid may be found in the peritoneal tive in delineating these malformations ( Pellerito cavity due to spillage of genital secretion/menstrual et al. 1992; Rosenberg et al. 1986). In our experience blood via the fallopian tubes. Repeated backfl ow traditional vaginography is restricted in value by of menstrual blood results in endometriosis and only demonstrating the inner contour of the vagina chronic epithelial tubal changes that jeopardize fer- (Gassner 2004). Frequently the uterus does not tility (Fig. 7.14). opacify, and the proximal impression of the cervix/ cervices or the lateral impression caused by an Diagnostic imaging of vaginal anomalies. Vaginal obstructed hemivagina may at times be diffi cult and anomalies without obstruction are usually asymp- confusing. Filling the vagina with either ultrasound tomatic unless they represent a mechanical obstacle contrast agents or plain salt solution combined with during intercourse or delivery. Either fl uid fi lling of ultrasound, however, overcomes these problems. In the vagina under sonographic guidance or tradi- our experience, fl uid instillation into either the blad- tional vaginography with contrast material is effec- der or the rectum or both signifi cantly increases the

Fig. 7.14a–c. Imperforate hymen with hydrometrocolpos and ascites due to spillage of genital secretions via the fallopian tubes into the peritoneal cavity. a,b Sagittal scans: the vagina (V) as well as the uterus (U) are dilated with broad communication through the cervical ostium (open arrowheads). The vagina shows a fl uid-debris level (closed arrowheads). c Distended, fl uid-fi lled abdomen. The air- fi lled loops of bowel cluster in the center of the abdomen. The lateral edge of the liver (arrowheads) is visible

b c

FOT2.indb 149 21.01.2008 14:06:19 150 T. E. Geley and I. Gaßner

performance of ultrasound by generating “sonographic windows” surrounding the uterus and vagina (Kiechl-Kohlendorfer et al. 2001). Filling the vagina in a newborn is performed via an 8-F feeding tube. A catheter of adjusted size is used in older girls. Simultaneously performed transabdominal or perineal ultrasound delineates the internal anatomy and patency of the vagina, the presence of one or two cervices, and allows the differentiation of a cystic mass being related to an obstructed vagina, an ureterocele, renal cysts (multicystic dysplastic kidney) (Fig. 7.8), or a dilated Gart- ner’s duct or a Gartner’s duct cyst. Gartner’s duct cysts are usually asymptomatic, do not exceed 2 cm in size, and typically exhibit a hypoechoic, sharply delineated cystic structure in close proximity to the anterolateral wall of the cervix (Rosenfeld and Lis Fig. 7.15. Normal ovarian appearance in the neonate. Trans- 1993). In the rare cases of the ureteral bud failing verse scan: the ovary contains multiple follicular cysts to separate from the wolffi an ducts, a single ectopic ureter may terminate directly or via Gartner’s duct or a Gartner’s duct cyst into the bladder neck, the a few months after birth. Ovarian cysts are thought urethra, the vaginal vestibule, or the vagina itself to be caused by maternal hormonal stimulation and (Currarino 1982). A single ectopic ureter is always have been found associated with hypersecretion of accompanied by ipsilateral renal hypoplasia, dys- placental hCG or increased placental permeability plasia, or agenesis ( Gharagozloo and Lebowitz to hCG (Müller-Leisse et al. 1992). 1994). Furthermore, an increased frequency of ovarian cysts is found in infants of diabetic mothers or Conclusion mothers who had toxemia or a large placenta com- plicating Rh sensitization as well as in infants suf- In the evaluation of müllerian duct anomalies in fering from adrenogenital syndrome (Silverman neonates and adolescent girls, sonography is the and Kuhn 1993; Topaloglu et al. 1997). most useful fi rst-step examination technique. In Great variations in the size of ovarian cysts are all patients with congenital malformations of the well documented, and they may occupy nearly the inner genitalia, the urinary tract needs to be eval- whole of the abdomen. According to their sono- uated. graphic morphology, two forms of ovarian cysts are described: simple and complex cysts. Although simple cysts are purely cystic without internal echoes, complex cysts, which result from salpin- gotorsion and subsequent ovarian infarction or 7.4 hemorrhage into a simple cyst, may show a fl uid- Ovarian Cysts debris level, a retracting clot, or thick septa. Due to autoamputation complex, cysts may be found any- Congenital ovarian cysts in the fetus and newborn where in the abdomen. Up to 30% of large simple used to be considered uncommon. With the intro- cysts undergo torsion, which most often happens duction of ultrasound as a screening procedure prior to birth. Torsion of an ovarian cyst occur- during pregnancy, the detection of both small and ring in postnatal life may be asymptomatic or may large cysts has increased. The presence of small fol- cause fever, irritability, vomiting, leukocytosis, and licular cysts is a common and normal fi nding in abdominal tenderness. Hemorrhage within an ovar- neonatal ovaries and can already be seen after the ian cyst may also occur without signs of torsion. 26th week of gestation in prenatal ultrasound. They Lower abdominal pain and tenderness are common are usually less than 1 cm in diameter (Fig. 7.15), features in these cases (Silverman and Kuhn 1993). contain clear fl uid, and resolve spontaneously within Controversy still exists as to whether conservative

FOT2.indb 150 21.01.2008 14:06:20 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 151

(close observation), intermediate (percutaneous Conclusion needle aspiration of large simple cyst under sonographic guidance, percutaneous drainage of com- The presence of small ovarian follicular cysts is plex cysts), or aggressive (surgical removal) therapy a normal ultrasound fi nding whatever the age. In is more appropriate. Müller-Leisse et al. (1992) neonates cysts may be found to be rather promi- demonstrated considerable regression of the ovar- nent due to maternal hormonal stimulation. ian cysts in almost all of their conservatively treated patients, regardless of the sonographic appearance of the cyst and, therefore, recommend conservative treatment in asymptomatic patients and percutaneous puncture of space-occupying cysts. 7.4.1 Ovarian cysts, however, that compromise bowel Diagnostic Imaging of Ovarian Cysts function, have ruptured and cause ascites or hemo- peritoneum, or require biopsy for histological exam- Ultrasound has proven reliable in differentiating ination due to their unspecifi c appearance, have to be simple cysts (unilocular-transonic) from complex surgically evaluated (Aslam et al. 1995). If surgical cysts (fl uid–debris level, retracting clot, thick septa) exploration is performed every attempt to salvage (Figs. 7.16, 7.17). Simple cysts should be monitored the gonad should be made. Viable ovarian tissue for spontaneous resolution and may be aspirated may still be present even if macroscopically invisible under sonographic guidance if the threat of second- (Brandt et al. 1991; Brandt and Helmrath 2005). ary torsion is considerably high. Bilateral ovarian cysts in older girls are often Complex cysts may present anywhere in the abdo- found in association with cystic fi brosis, untreated men and frequently bleed during or immediately hypothyroidism (Lindsay et al. 1983), Cushing syn- after birth so that a fl uid–sludge level or an evolv- drome, and other endocrinopathies with increased ing clot can be seen (Figs. 7.16, 7.17). In some cases, circulating androgen levels. Bilateral ovarian percutaneous puncture of the cyst can be diagnostic enlargement with discrete cysts has been seen in in showing evidence of increased estradiol in the children with McCune-Albright syndrome (fi brous withdrawn fl uid. dysplasia, patchy cutaneous pigmentation, sexual Complex ovarian masses need to be differen- precocity) (Rieth et al. 1981) and in patients suffer- tiated from cystadenoma, pelvic infl ammatory ing from polycystic ovarian disease. disease, neoplasm, enteric duplication cysts, and In polycystic ovarian disease, both of the gener- benign teratomas. Sonography permits the cor- ally enlarged ovaries contain many small follicular rect diagnosis with a high confi dence level in cysts (2–6 mm), but larger cysts may also be pres- simple cysts, and occasionally a specifi c diagno- ent. Polycystic ovarian syndrome (Stein-Leventhal sis of ovarian teratoma can be made when highly syndrome) is characterized by the association of echogenic foci with shadowing are demonstrated polycystic ovaries with irregular menses, prolonged within a complex adnexal mass. However, ultra- uterine bleeding, amenorrhea, anovulation, and sound was not found to be reliable to distinguish often hirsutism and obesity. The clinical manifes- between hemorrhagic cysts and benign teratoma tation of this syndrome begins at or shortly after in cases where no calcifi cation or fat was present puberty. (Wu and Siegel 1987). The sonographic appear- Unilateral or bilateral ovarian follicular cysts of ance of benign ovarian teratomas is a predomi- various sizes are frequently observed in girls with nantly cystic structure containing focal areas of precocious puberty (onset of secondary sexual soft-tissue echogenicity and septation. In addi- characteristics before 8 years of age). These cysts tion, complicated ovarian cysts often have thick may either be secondary to ovarian stimulation by echogenic walls resulting from dystrophic calcifi - an increased level of circulating pituitary gonado- cation associated with infarction. These sonogra- tropins (central precocious puberty) or functional phic appearances may be indistinguishable from cysts similar to those seen in normal girls (partial the typical “thick-walled sign or double-wall sign” precocious development). However, in some cases a described for enteric cysts (Godfrey et al. 1998). large ovarian cyst may assume an autonomous func- Further investigations such as CT or MR imag- tion and be responsible for precocious puberty due ing are sometimes inevitable to provide a specifi c to excessive estrogen production. diagnosis in these cases.

FOT2.indb 151 21.01.2008 14:06:21 152 T. E. Geley and I. Gaßner

Conclusion Sonography is a reliable imaging technique to dif- ferentiate between simple and complex ovarian cysts. Unrelated to their sonographic appearance, ovarian cysts show a high potential for self-resolution. Conservative treatment with sonographic monitoring seems appropriate for most cases.

7.5 Lower Urinary Tract Anomalies of Urogenital Sinus

The most common urogenital sinus malformations a radiologist will come across are patients suffering from female hypospadias (simple urogenital sinus), intersexual conditions, and cloacal malformation (urogenital sinus associated with anorectal malformation) (Fig. 7.18). Fig. 7.16. Congenital ovarian cyst in a newborn of diabetic Urogenital sinus is suspected during physical mother complicated by torsion. Longitudinal sonogram of examination of a newborn with a normally placed the right hemiabdomen shows a large cyst with low-level echoes, a ﬂ uid-debris (blood) level, and an undulating thick anus in association with either ambiguous genita- membrane (ﬁ brin; arrowheads). The cyst decreased in size lia or a normal external genitalia, but only a single and resolved completely perineal opening within the vestibulum. It is either

a c

Fig. 7.18a–d. Schematic presentation of lower urinary tract anomalies of the urogenital sinus. a Distal female hypospadia: the urethral meatus lies in the roof of the vagina. b Proximal female hypospadia. c Urogenital sinus. d Persis- tent cloaca. The most common anatomy of persistent cloaca Fig. 7.17. Congenital ovarian cyst complicated by torsion. is shown. There is a urogenital sinus; the vagina enters just Transverse scan shows the large cyst with low-level echoes, below the bladder neck, the rectum enters just below the a ﬂ uid-debris level, as well as a huge retracting clot (arrow- vagina. The conﬂ uence level can be high, intermediate, or heads). The cyst and clot resolved completely low

FOT2.indb 152 21.01.2008 14:06:21 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 153

isolated or found in association with chromosomal may, therefore, be asymptomatic or cause symptoms and hormonal abnormalities or as a cloacal vari- such as postmicturition incontinence and imper- ant. Neonates with urogenital sinus frequently have fect control, recurrent urinary tract infections, and ambiguous genitalia, since a main cause of this mal- urethral syndrome (referring to isolated urethritis formation stems from virilization of a female fetus with symptoms of increased frequency, pain during or an intersex anomaly. However, urogenital sinus micturition, urgency, and dyspareunia) once sexual may also result from incomplete development of the intercourse has commenced (Van Bogaert 1992). lower vagina and the external genitalia may appear The more severe cases of proximal hypospadias completely normal (Marshall et al. 1979). often show a narrowing of the urethra with signs In patients with ambiguous genitalia, determi- of urinary outﬂ ow obstruction and are commonly nation of the sex has to be performed using bio- associated with cloacal anomalies and female pseu- chemical, genetic, and radiological studies in order dohermaphroditism (Knight et al.1995). to exclude the life-threatening salt-losing form of adrenogenital syndrome and to provide adequate 7.5.1.1 information to the parents. Diagnostic Imaging of Female Hypospadias

In mild forms of female hypospadias the urethral 7.5.1 meatus is on the roof of the vagina just inside the Female Hypospadias introitus and might be entirely overlooked unless attempts to catheterize the urethra, usually for In female hypospadias the urethral meatus is posi- radiologic evaluation of the urinary tract, are frus- tioned in the anterior wall of the vagina (Figs. 7.18, trated by the inability to locate the meatus (Balk 7.19). Merguerian and McLorie (1992) regard et al. 1982). In these patients the urethra must be female hypospadias as a mild form of urogenital catheterized blindly using a catheter with a curved sinus. Currarino (1986) and Knight et al. (1995) tip (Coudé catheter). To rule out associated malfor- describe female hypospadias as an abnormality of mations both kidneys, the uterus and the vagina of the urethra itself caused by a defect in the differ- these patients should be examined. The more severe entiation of either the wolfﬁ an ducts, which form cases of female hypospadias are usually part of a the dorsal part of the urethra, or the urogenital complex urogenital malformation and diagnostic sinus, which develops into the distal third of the evaluation will, therefore, be discussed below. vagina. Differentiation defects of the wolfﬁ an duct lead to the development of the more severe proximal Conclusion hypospadias, whereas developmental anomalies of the urogenital sinus result in the less severe distal Inability to locate the urethral meatus in a little hypospadias. girl may be due to the presence of female hypospadias. In these patients the urethral meatus is Distal hypospadias is more likely to have a ure- positioned in the anterior wall of the vagina and thra of normal diameter with no meatal stenosis and catheterization has to be attempted blindly.

7.5.2 Urogenital Sinus in Disorders of Sex Development

Disorders of the external genitalia are especially troubling for parents because of the unconscious emotional signiﬁ cance of these reproductive struc- ab tures, and it is the role of the radiologist to assist in assigning the correct gender of the neonate and to Fig. 7.19a,b. Schematic representation of female hypospadia. a The perineal anatomy shows a female phenotype but anticipate and diagnose any life-threatening condi- no urethral opening. b The urethral meatus is in the roof tions related to intersexual states. According to the of the vagina Consensus statement on management of intersex

FOT2.indb 153 21.01.2008 14:06:22 154 T. E. Geley and I. Gaßner

2006, the three major types of disorders of sex devel- Placental aromatase defi ciency. This results from opment (DSD) with ambiguous genitalia are referred a very low aromatizing activity of the placenta and to as 46, XX DSD, 46, XY DSD and ovotesticular DSD thus fails to convert androgens derived from fetal (Hughes et al. 2006). dehydroepiandrosterone into estrogens (Shozu et al. 1991; MacGillivary et al. 1998). 7.5.2.1 46, XX Disorders of Sex Development Virilizing maternal tumors. These include adrenal adenoma, androblastoma, luteomas, and Kruken- In most instances 46, XX disorders with ambigu- berg tumors and are reported to cause fetal vir- ous genitalia (former female pseudohermaphrodit- ilization. In cases of unclear hermaphroditism, ism) result from either exposure of a female fetus to evaluation of the mother should always include excessive androgens or sex chromosome disorders. measurement of her plasma androgen levels. The most common causes of androgen excess are congenital adrenal hyperplasia, followed by placen- Administration of androgenic drugs to pregnant tal aromatase defi ciency, masculinizing maternal women. Over the past couple of years this mainly iat- hormones, and administration of androgenic drugs rogenic problem has been signifi cantly reduced by to women during pregnancy. The increased level of replacing virilizing progestational compounds with androgens within the fetal blood stream causes vir- nonvirilizing analogs in the treatment of threat- ilization of the external genitalia, which may vary ening abortion. The frequent cause of ambiguous from minimal phallic enlargement of the clitoris to genitalia in sex chromosome DSD is mixed gonadal almost complete masculinization (Fig. 7.20). The dysgenesis. degree of masculinization of the fetus is thought to be related to the time and amount of androgen Mixed gonadal dysgenesis is a condition of abnormal exposure. If the androgen stimulus is received after and asymmetrical gonadal development, and/or sex 12 weeks of gestation, only clitoral hypertrophy will chromosomal mosaicism, as well as retained mul- occur (Merguerian and McLorie 1992). Earlier lerian ducts. A number of abnormalities have been androgen exposure results in urogenital sinus and reported in the karyotype, most commonly a mosa- a higher degree of ambiguity of the external geni- icism 45,X/46, XY. The phenotypical expression may talia. At birth these patients present with marked be ambiguous, or male, or female depending on the clitoral enlargement, variable degree of labioscrotal extent of the mosaicism. The gonads may not be fold fusion and rugation. The opening of the uro- symmetrical, thus the development of the müllerian genital sinus at the clitoral base may mimic penile duct and wolffi an duct may be asymmetrical, too hypospadias. (Donahoe et al. 1979). In the presence of dysgenetic gonadal tissue and Y chromosome material, there Congenital adrenal hyperplasia. This is caused by a is a high risk of the development of tumors such as family of autosomal recessive disorders of adrenal gonadoblastomas and seminoma-dysgerminomas steroidogenesis leading to a defi ciency of cortisol. with the risk exceeding 50% as the 3rd decade is Lack of glucocorticoid hormone causes an increase approached. Removal of the gonads is usually indi- in corticotropin, hyperstimulation of the fetal adre- cated. nal gland, and excessive androgen synthesis. One out of three adrenal enzymes involved in the path- 7.5.2.2 way on which glucocorticoids are synthesized is 46, XY Disorder of Sex Development affected. The condition 21-hydroxylase defi ciency counts for 90–95%, and a defect of 11E-hydroxylase 46, XY disorder of sex development with ambiguous is found in 5–8% of cases (New 2003). The remain- genitalia (former male pseudohermaphroditism) is ing patients show defects of other enzymes involved most frequently caused by an abnormal plasma tes- in steroidogenesis. Due to impaired aldosterone bio- tosterone level or an abnormal testosterone response. synthesis, salt-losing symptoms are common in 21- The most common causes are disorders in androgen and 3E-hydroxysteroid dehydrogenase defi ciencies synthesis or action. and usually present soon after birth. Owing to allelic variants, severe and mild forms are described for 5-alpha reductase defi ciency is an androgen biosyn- each defect (Chan-Cua et al. 1989). thesis defect that blocks the transformation of testos-

FOT2.indb 154 21.01.2008 14:06:23 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 155

a b

Fig. 7.20a–c. Congenital adrenal hyperplasia with virilization of the external genitalia and urogenital sinus with vaginal stenosis in a 1-day-old female. a Right longitudinal sonogram; b left axial sonogram. The adrenal gland is enlarged with the so-called cerebriform pattern (resem- bling cerebral cortex). c Longitudinal pelvic scan conﬁ rms the presence of uterus (arrowheads). There is moderate d hydrometrocolpos (asterisks) due to urogenital sinus with vaginal stenosis. d The bladder is catheterized. Contrast material ﬁ lls the bladder (B) and during micturition the vagina (V). Stenotic vaginal communication (open arrow). Urogenital sinus opening (closed arrow)

terone into the more potent 5-alpha dihydrotestos- opment of the epididymis, vas deferens, seminal ves- terone (DHT). The affected 46XY individuals have icle, and ejaculatory duct, but also a pseudovagina high normal to elevated plasma testosterone levels (Imperato-McGinley and Zhu 2002). with decreased DHT levels and elevated testosterone/DHT ratios. DHT is necessary to exert andro- Androgen insensitivity syndrome (AIS) is also called genic effects farther from the site of testosterone testicular feminization and results from a complete production. A 5-alpha reductase deﬁ ciency results or partial absence of cytoplasmic receptors for tes- in a disorder characterized by female phenotype or tosterone in target tissues (Holterhus et al. 2005). It severely undervirilized male phenotype with devel- is an X-linked (band Xq11-q12) disorder with an inci-

FOT2.indb 155 21.01.2008 14:06:23 156 T. E. Geley and I. Gaßner

dence of 1 in 62,000 male births. The feminization 7.5.2.4 is a consequence of increased testicular secretion of Diagnostic Imaging of Urogenital Sinus Anomalies oestradiol, peripheral conversion of androgens to oestradiol and a lack of testosterone function during In congenital adrenal hyperplasia (Willi 1991; fetal development. Serum LH and FSH are elevated as Chertin et al. 2000) the primary task of the radi- testosterone is ineffective at the hypothalamus. The ologist is to demonstrate the level of communication syndrome is characterized by a 46, XY karyotype and between the vagina and the urethra, the anatomy of negative sex chromatin. It is divided into two main the internal genitalia and to rule out kidney anom- categories: complete (CAIS) and partial (PAIS). CAIS alies and adrenal gland hyperplasia. Sonographic results in bilateral testes, absent or hypoplastic wolff- evaluation of the patient is usually the fi rst-step ian ducts, and female-appearing external genitalia imaging technique to provide detailed information with diminished axillary and pubic hair develop- on the urogenital system. Sonography is then to ment (Collins et al. 1993). be followed by conventional radiology using con- In PAIS the degree of sexual ambiguity varies trast material to visualize the exact anatomy of the widely from individual to individual. PAIS can malformation. Transabdominal ultrasound demon- include other disorders, such as Reifenstein’s syn- strates the internal genitalia, delineates müllerian drome (also known as Gilbert-Dreyfus syndrome or duct anomalies, and rules out any obstructions such Lubs syndrome), which is associated with hypospa- as hydrocolpos and hydrometrocolpos (Blask et dias, gynecomastia, and cryptorchism. al. 1991a), and allows investigation of the kidneys CAIS is rarely discovered during childhood, and adrenal glands at the same time. Urinary tract unless a mass is felt in the abdomen or groin that anomalies are common and include renal agenesis, turns out to be a testicle. Most with this condition ectopia, and cystic dysplasia as well as uni- and bilat- are not diagnosed until they fail to menstruate or eral hydronephrosis, vesicoureteral refl ux, and signs they try to become pregnant. PAIS, however, is often of urinary outfl ow obstruction (Woolf and Allen discovered during childhood because the affected 1953). Enlargement of the adrenal cortex occurs in child has both male and female physical character- many, but not all babies with congenital adrenal istics and/or ambiguous genitalia such as partial hyperplasia. Demonstration of enlarged adrenal fusion of the outer vaginal lips, an enlarged clitoris, glands with a wavy confi guration of their limbs, or a short, blind-ending vagina. however, is highly suspicious of congenital adrenal hyperplasia even before biochemical or genetic data 7.5.2.3 can be obtained (Fig. 7.20) (Teele and Share 1991; Ovotesticular Disorder of Sex Development Hernanz-Schulman et al. 2002; Barwick et al. 2005). Ovotesticular disorder of sex development (former After the patient has been evaluated by ultra- true hermaphroditism) is a very rare form of inter- sound, fl uoroscopic studies with water-soluble con- sex disorder characterized by the presence of both trast material are required to examine the exact ovarian and testicular tissue in the same individual. anatomy of the malformation (Fig. 7.20). Barium There may be an ovary on one side and a testis on the paste or another opaque material is useful for mark- other, but more commonly one or both gonads is an ing the external orifi ce on the perineum and the ovotestis containing both types of tissue. External urethra and/or the urogenital sinus is catheterized. genitalia are often ambiguous, the degree depend- If the catheter enters the bladder, voiding cysto- ing mainly on the amount of testosterone produced ureterography should be performed in the lateral by the testicular tissue between 8 and 16 weeks of position to demonstrate the urethra as well as the gestation. It is rare for both types of gonadal tissue vagina during micturition and to rule out vesicoure- to function. teral refl ux. If only the vagina is fi lled, however, the catheter should be left in place and a second cath- Conclusion eter passed anteriorly into the urogenital sinus in an attempt to catheterize the urethra. The relative posi- Phenotypic sex differentiation is determined by tion of the vaginal orifi ce both to the urethra and to hormonal products of the gonads. Anomalous the vestibulum can then be demonstrated. hormone production during fetal development Using ultrasound and contrast studies, a defi ni- frequently results in ambiguous genitalia. tive diagnosis of anatomical features and associated

FOT2.indb 156 21.01.2008 14:06:24 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 157

genitourinary tract malformations can be made. Vaginal anomalies include biﬁ d vagina, unilat- More invasive imaging techniques such as endos- eral obstruction of one hemivagina, distal vaginal copy and MR imaging can thus frequently be post- stenosis or atresia, absence of the vagina, a mislocal- poned until shortly prior to surgical repair. ized retrorectal vagina, and a biﬁ d vagina commu- In androgen insensitivity syndrome ultrasound nicating widely with the trigonal area of the bladder will demonstrate an absent uterus, no or a blind (Fig. 7.22) (Jaramillo et al. 1990; Tolete-Velcek ending vagina, and testes located in the inguinal et al. 1989). canal, labia, or intra-abdominal. Coexistence with Apart from the incomplete cloaca with two peri- urologic abnormalities has to be is expected such as neal openings, most patients present with a single unilateral renal agenesis (Tokgoz et al. 2006). The perineal opening. The perineal anatomy varies from patient is at increased risk of undergoing malig- an almost normal female phenotype (Fig. 7.23) to a nant transformation of the undescended gonad. The gonads should not be removed until puberty and growth are complete, but closely monitored sono- graphically during childhood.

Conclusion Narrowing differential diagnosis of the possible cause of urogenital sinus as well as demonstration a d of its anatomical features can be achieved at a high conﬁ dence level using contrast studies and ultrasound to assess pelvic structures and the adrenal glands.

7.5.3 Cloacal Malformation b e

The cloacal malformation is the most complex type of imperforate anus with conﬂ uence of the rectum, vagina, and bladder in a urogenital sinus. Cloaca is exclusively seen in phenotypic females and occurs in one of every 40,000–50,000 newborns. Cloaca should not be confused with cloacal exstrophy, a malformation due to a failed closure of the lower abdominal wall seen in boys and girls. The diagnosis of cloacal c f malformation includes a wide spectrum of pelvic Fig. 7.21a–f. Schematic presentation of cloacal malforma- and perineal anomalies (Jaramillo et al. 1990; tion variants. a Incomplete cloacal malformation: a persis- Hendren 1998). At the mild end of the spectrum is tent urogenital sinus opening is found adjacent to an ante- a persistent urogenital sinus opening with an anteriorly placed anus. b Posterior cloaca: the urogenital sinus riorly placed anus adjacent to it (incomplete cloaca), derives posteriorly and opens in the anterior rectal wall at the anus or immediately anterior to it. Jaramillo et al. while in more severe malformations all three tracts (1990) characterize the anatomy of persistent cloaca accord- converge inside the pelvis. Variants of the cloacal ing to its urinary-cloacal or urinary-rectal communication malformations include the presence of an accessory pattern. Urinary-cloacal communication is called either ﬁ liform channel or sinus that connects the blad- urethrocloacal or vesicocloacal. c Urethrocloacal commu- der or urethra to the perineum, anomalies of the nication: the urethra empties into the proximal end of the vagina, and the so-called posterior cloaca, where the cloaca and is well formed. d Vesicocloacal communication: the urethra is rudimentary or absent. Rectal communication urogenital sinus is posteriorly placed and found to is called either vaginal or cloacal. e Vaginal communication open either into the orthotopic rectum or perineally of the rectum: the rectum usually joins the vagina low on its close to the normal anus (Pena and Kessler 1998) posterior wall. f Cloacal communication of the rectum: the (Fig. 7.21). rectum joins the cloaca

FOT2.indb 157 21.01.2008 14:06:24 158 T. E. Geley and I. Gaßner

Except for the rare instances of incomplete cloaca, immediate colostomy is required to prevent fecal contamination of the urinary tract and renal damage, which is the most signifi cant potential cause of morbidity and mortality in these patients. Obstruction of the cloaca may occur at any level and acdetermines whether the proximal distended urinary and/or genital system is fi lled solely with genital secretions or contains urine and/or meconium as well (Fig. 7.22). In patients with hydronephrosis or severe obstruction of the vagina, early drainage is required. Immediate correction of severe vesicoure- bdteral refl ux or another life-threatening uropathy is essential. In cases of tethered cord, neurosurgical Fig. 7.22a–d. Schematic presentation of cloacal variants and release can prevent neuronal defi cits during growth, genital anomalies. a Bifi d vagina and uterus, the rectal fi s- but usually fails to alleviate already established neu- tula enters at the base of the septum dividing the vagina. rological defi cits. b Distal vaginal stenosis or atresia leading to hydrometrocolpos. c Bifi d uterus and vagina, unilateral obstruction and Defi nitive correction of the cloaca can now be hydrometrocolpos. d Obstruction of the urogenital sinus performed between the ages of 6 and 24 months resulting in distention of the vagina by a combination of (Hendren 1998), and the prognosis of infants with genital secretion, meconium, and urine cloacal malformation has improved signifi cantly during recent years due to surgical repair techniques pioneered by Hendren. rudimentary phallic structure with poorly formed labia (Hendren 1998). Additional pelvic anomalies include fusion defects of the müllerian ducts, with Conclusion a duplication of the uterus in 55% of patients and obstruction of the genital tract in 25% (Jaramillo The diagnosis of cloacal malformation includes a et al. 1990; Blask et al. 1991a,b; Tolete-Velcek wide spectrum of pelvic and perineal anomalies. et al. 1989). Major renal anomalies such as renal Associated malformations of the inner genitalia and urinary tract need to be considered. agenesis, multicystic dysplasia, or renal ectopia are frequently associated with cloacal malformation. Vesicoureteral refl ux usually occurs bilaterally and is sometimes associated with bladder diverticula and ectopia of the ureter (Jaramillo et al. 1990; McLorie et al. 1987). The ureteral ostium might then be found in a lateral or inferior location in the bladder, the vagina, or the cloaca. In cases of functional bladder outlet obstruction, hydronephrosis is common (Rich et al. 1988; Hassink et al. 1996). Fig. 7.23a–k. Cloacal malformation with uterus didel- Furthermore, cloacal malformation can be associ- phys. a The perineal anatomy shows a female pheno- ated with anomalies of the pelvic osseous structures type, but only a single perineal opening. Meconium is seen within the ostium of the cloaca. b Plain X-ray. such as sacral agenesis or hypoplasia, dysraphism, The vagina is dilated (closed arrowheads) and contains and pubic diastasis. Pubic diastasis, if wider than air. A sagittal vaginal septum is visible (open arrow- 4 cm, is frequently associated with either duplica- heads). c Transverse pelvic scan: right (R) and left (L) tion of the bladder or a common vesicovaginal or cervix uteri behind the empty bladder. d Transverse vesicocloacal chamber. In addition, lower spinal pelvic scan at lower level than c shows the right and cord abnormalities such as lipomyelomeningocele, left vagina (V), urethra (open arrowheads), and the rectocloacal fi stula (arrowhead). e Axial MR view high cord, and most frequently (affecting one-third (T2-weighted) of the gadolinium-fi lled vagina shows of all patients with cloacal malformation) teth- the sagittal vaginal septum with the rectocloacal fi s- ered cord (Karrer et al. 1988; Metts et al. 1997; tula (closed arrowhead) and the dilated vagina halves Barkovich 1999) are found. with air-fl uid levels. The open arrowhead marks the

FOT2.indb 158 21.01.2008 14:06:25 a b c

d e f

ghi

catheter. f Longitudinal pelvic scan shows the cloacal fi stula (asterisk), rectum (R), and vagina (V). g,h Frontal and lateral view after contrast fi lling of the colon via colostomy demonstrates the rectum (R), the right and left vagina (V), and the rectocloacal fi stula (arrowheads). i Transperineal sagittal scan: urethra (U), vagina (V), and rectum (R) converge to a short common cloacal channel (arrows). j Lateral view after contrast fi lling: bladder (B), vagina (V), and rectum (R). Three separate catheters are inserted through the single perineal opening. k Lateral view during voiding after removal of the catheters in rectum and vagina. The short common cloacal channel is clearly demonstrated (arrows). Bladder (B), vagina (V), rectum (R) jk

FOT2.indb 159 21.01.2008 14:06:25 160 T. E. Geley and I. Gaßner

7.5.3.1 up to 43%. The spinal cord can either be examined Diagnostic Imaging of Cloacal Malformation by means of spinal ultrasound during the neonatal period or, if necessary, using MR imaging later in Prenatal ultrasound often fails to provide an early life (Barkovich 1999). diagnosis, and the large, sometimes septated, fl uid- Sonographic features of spinal anomalies in fi lled pelviabdominal mass is often mistaken for patients with cloacal malformations are either a the urinary bladder. After delivery the diagnosis of high-lying plump conus or a tethered cord with a cloacal malformation is made when, in addition to thickened fi lum terminale (greater than 2 mm at an absent anus, only one perineal orifi ce is found L5-S1), a low-lying conus medullaris (the tip of the between the labia (Fig. 7.23). These patients need conus lies below the level of L2), a posterior posi- urgent referral to the pediatric radiology depart- tion, and a restricted motion of the conus and fi lum ment for early defi nition of the abnormal anatomy terminale within the thecal sac. In some cases of and detection of associated malformations or poten- tethered cord, no distinct fi lum can be seen, but the tial life-threatening complications. spinal cord is markedly elongated, extending down- Ultrasound is the most effi cient fi rst-step imag- ward to the lower end of the dural sac (Fig. 7.24). This ing technique in the diagnostic work-up of these feature is particularly common in caudal regression patients. Early after birth, no or only a small syndrome, frequently associated with anal atresia amount of intestinal gas will be present and a and cloacal malformation (Barkovich 1999). clearer documentation of the intrapelvic structures After having obtained a good sonographic over- can be obtained (Fig. 7.23). A pelvic mass, which is view of the pelvic anatomy, radiological examina- almost always a distended vagina and/or uterus, tion should then be continued with plain radio- can readily be visualized (Blask et al. 1991a). graphs performed a couple of hours after birth to A fl uid-debris level is frequently seen and the provide evidence of any distal bowel obstruction level of obstruction can be determined. If there is due to the accumulation of air (Fig. 7.23). Gas seen obstruction of the common outlet, retrograde fl ow in the bladder indicates urinary-intestinal com- via the fallopian tubes may result in accumulation munication. A pelvic mass is usually a distended of intra-abdominal fl uid. Depending on the level of vagina and/or uterus, secondary to obstruction. If obstruction, this fl uid may consist of genital secre- this mass contains gas it is a sign of a rectovaginal tion only (obstruction lies above the communica- communication. Linear calcifi cations in the abdo- tion between the bladder, rectum, and vagina) or men along the peritoneal surface are signs of cal- contains urine and/or meconium as well. Vaginal cifying peritonitis, which is not necessarily a result and bladder duplication as well as malformations of of congenital intestinal perforation, but can occur the uterus can be visualized. In cases of duplicated whenever either meconium (Jaramillo et al. 1990) genital structures, care should be taken to docu- or genital secretion (Nidecker and Humphry 1978; ment any obstruction (Tolete-Velcek et al. 1989; Ceballos and Hicks 1979) spills into the peritoneal Blask et al. 1991a). The distance between the blind cavity via the fallopian tubes. Granular abdominal end of the rectum and the perineum can accurately calcifi cations suggest calcifi ed intraluminal meco- be measured by transperineal ultrasound (Teele nium (enteroliths) due to mixing of urine and meco- and Share 1997). The sonographic evaluation of nium that are commonly associated with vaginal the newborn is completed by analysis of the kidney atresia or stenosis and rectovesical or rectourethral and the spinal cord. The result of the sonographic communication. examination of the upper urinary tract is used to The next step in the imaging process is fl uoro- choose further diagnostic tests, such as scintigra- scopic studies using water-soluble contrast mate- phy and intravenous urography. If not put in the rial to visualize the often unpredictable and erratic hands of an investigator highly experienced with courses of the communication between the multiple MR imaging in young infants, we still regard intra- structures and to provide functional information venous urography as superior to MR imaging in about refl ux and competence of the urinary sphinc- delineating all relevant features of urinary tract in ter (Fig. 7.23). Contrast material is injected into cloacal malformation. the cloaca using an 8-F feeding tube if the perineal In every patient with cloacal malformation, the opening is small. A wider opening may need partial spinal cord needs to be evaluated, since anomalies sealing using the balloon of a Foley catheter or a of the lower spinal cord occur with an incidence of nipple (the Poznanski technique). Accessory peri-

FOT2.indb 160 21.01.2008 14:06:28 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 161

a b

Fig. 7.24a,b. Cloacal malformation with a tethered cord and a high-lying plump conus. a Longitudinal scan shows that the cord (open arrowheads) extends into the sacral canal. b Longitudinal scan shows a high-lying stubby conus (arrowheads)

neal openings should be sought. A second rudimen- onstrate the narrow communication between the tary urethra (phallic urethra) is expected in cases organ systems. where an additional small opening is found at the Some authors recommend using MR imaging to base or the tip of the clitoris (Jaramillo et al. 1990). delineate the anatomy of the inner genitalia prior to Imaging during injection should begin in the lateral defi nitive surgical repair of the cloacal malforma- projection to display the various communications. tion (Metts et al. 1997; Tolete-Velcek et al. 1989). Frontal projections are useful to delineate vaginal or We, however, have never obtained much additional bladder duplications. A competent urethral sphinc- information from MR imaging and do not believe ter can be expected when the bladder fails to opacify, that MR imaging, which requires sedation of the and vaginal obstruction or atresia is documented patients, should be performed routinely during the if contrast material fails to visualize the vagina. It work-up of cloacal malformation. might sometimes be diffi cult to distinguish between the bladder and the vagina. Refl ux into a ureter or a Conclusion urachal remnant helps to identify the bladder; a cervical impression or a septum identifi es the vagina. To assess pelvic structures in cloacal malforma- However, in our experience this cervical impression tion, ultrasound should be performed as soon as possible after birth since no or only a small is often diffi cult to observe. amount of intestinal gas will be present. Fluoro- Following the injection into the cloaca, an attempt scopic studies to demonstrate the complex anat- to catheterize the bladder should be made to perform omy as well as to evaluate the urinary tract and a voiding cystourethrogram, the only way to rule out the inner genitalia for diagnostic purposes are vesicoureteral refl ux. In some cases catheterization mandatory. of the bladder may be diffi cult and needs to be sup- ported by the use of a Coudé catheter, cystoscopy, or suprapubic puncture. The rectum frequently fails to opacify after the References injection of contrast material into the cloaca. In patients who have already had a colostomy, contrast Aaronson IA (1992) Sexual differentiation and intersexu- material can be directly injected into the distal limb ality. In: Kelalis PP, King LR, Belman AB (eds) Clini- cal pediatric urology, 3rd edn. Saunders, Philadelphia, of the colostomy prior to retrograde cloacal injec- pp 977–1014 tion. This technique regularly demonstrates the Aslam A, Wong C, Haworth JM, Nobelett HR (1995) Autoam- level of rectal occlusion and the presence of commu- putation of ovarian cyst in an infant. J Pediatr Surg nication between other pelvic structures, making 30:1609–1610 Balk SJ, Dreyfus NG, Harris P (1982) Examination of genitalia further cloacal injections unnecessary (Fig. 7.23). in children: the remaining taboo. Pediatrics 70:751–753 Most commonly, a balloon catheter is used to inject Barkovich AJ (1999) Pediatric neuroimaging, 3rd edn. Lip- contrast material under moderate pressure to dem- pincott Williams & Wilkins, Philadelphia, pp 648–653

FOT2.indb 161 21.01.2008 14:06:29 162 T. E. Geley and I. Gaßner

Barwick TD, Malhotra A, Webb JA, Savage MO, Reznek RH Gruenwald P (1941) The relation of the growing Müllerian (2005) Embryology of the adrenal glands and its relevance ducts to the Wolffi an duct and its importance for the gen- to diagnostic imaging. Clin Radiol 60:953–959 esis of malformations. Anat Rec 81:1–19 Bazi T, Berjawi G, Seoud M (2006) Inguinal ovaries asso- Hartwig NG (1992) Pathoembryology: developmental pro- ciated with Mullerian agenesis: case report and review. cesses and congenital malformations. Thesis, State Uni- Fertil Steril 85:1510–1518 versity Leiden, The Netherlands Blask AR, Sanders RC, Gearhart JP (1991a) Obstructed Hassink EAM, Rieu PNMA, Hamel BCJ, Severijnen RSVM, vd uterovaginal anomalies: demonstration with sonography. Staak FHJ, Festen C (1996) Additional congenital defects I. Neonates and infants. Radiology 179:79–83 in anorectal malformations. Eur J Pediatr 155:477–482 Blask AR, Sanders RC, Rock JA (1991b) Obstructed utero- Hendren H (1998) Cloaca, the most severe degree of imper- vaginal anomalies: demonstration with sonography. forate anus. Ann Surg 228:331–346 II. Teenagers. Radiology 179:84–88 Hernanz-Schulman M, Brock JW, III, Russell W (2002) Brandt ML, Luks FI, Filiatrault D, Garel L, Desjardins JG, Sonographic fi ndings in infants with congenital adrenal Youssef S (1991) Surgical indications in antenatally diag- hyperplasia. Pediatr Radiol 32:130–137 nosed ovarian cysts. J Pediatr Surg 26:276–282 Holterhus PM, Werner R, Hoppe U, Bassler J, Korsch E, Brandt ML, Helmrath MA (2005) Ovarian cysts in infants Ranke MB, Dorr HG, Hiort O (2005) Molecular features and children. Semin Pediatr Surg 14:78–85 and clinical phenotypes in androgen insensitivity syn- Buttram VC, Gibbons WE (1979) Müllerian anomalies: a pro- drome in the absence and presence of androgen receptor posed classifi cation (an analysis of 144 cases). Fertil Steril gene mutations. J Mol Med 83:1005–1013 32:40–46 Hughes IA, Houk C, Ahmed SF, Lee PA, LWPES/ESPE Con- Ceballos R, Hicks GM (1979) Plastic peritonitis due to neona- sensus Group (2006) Consensus statement on manage- tal hydrometrocolpos: radiologic and pathologic obser- ment of intersex disorders. Arch Dis Child 91:554–563 vations. J Pediatr Surg 5:63–70 Imperato-McGinley J, Zhu YS (2002) Androgens and male Chan-Cua S, Freidenberg G, Jones KL (1989) Occurrence of physiology: the syndrome of 5alpha-reductase-2 defi - male phenotype in genotypic females with congenital ciency. Mol Cell Endocrinol 198:51–59 virilizing adrenal hyperplasia. Am J Med Genet 34:406– Jaramillo D, Lebowitz RL, Hendren WH (1990) The cloacal 410 malformation: radiologic fi ndings and imaging recom- Chertin B, Hadas-Halpern I, Fridmans A, Kniznik M, bu- mendation. Radiology 177:441–448 Arafeh W, Zilberman M, Farkas A (2000) Transabdomi- Jarcho J (1946) Malformation of the uterus: review of the nal pelvic sonography in the preoperative evaluation subject, including embryology, comparative anatomy, of patients with congenital adrenal hyperplasia. J Clin diagnosis and report of cases. Am J Surg 71:106–166 Ultrasound 28:122–124 Karrer FM, Flannery AM, Nelson MD, McLone DG, Raffens- Collins GM, Kim DU, Logrono R, Rickert RR, Zablow A, Breen perger JG (1988) Anorectal malformations: evaluation of JL (1993) Pure seminoma arising in androgen insensitiv- associated spinal dysraphic syndromes. J Pediatr Surg ity syndrome (testicular feminization syndrome): a case 3:45–48 report and review of the literature. Mod Pathol 6:89–93 Kiechl-Kohlendorfer U, Geley TE, Unsinn KM, Gassner I Currarino G (1982) Single vaginal ectopic ureter and Gart- (2001) Diagnosing neonatal female genital anomalies ner’s duct cyst with ipsilateral renal hypoplasia and dys- using saline-enhanced sonography. AJR Am J Roentgenol plasia (or agenesis) J Urol 128:988–993 177:1041–1044 Currarino G (1986) Large prostatic utricles and related struc- Kluth D, Hillen M, Lambrecht W (1995) The principles of tures, urogenital sinus and other forms of urethrovaginal normal and abnormal hindgut development. J Pediatr confl uence. J Urol 136:1270–1279 Surg 30:1143–1147 Donahoe PK, Crawford JD, Hendren WH (1979) Mixed Knight HML, Phillips NJ, Mouriquand PDE (1995) Female gonadal dysgenesis, pathogensis, and management. J Pe- hypospadias: a case report. J Pediatr Surg 30:1738–1740 diatr Surg 14:287–300 Koopman P (1995) The molecular biology of SRY and its Fielding JR (1996) MR imaging of Müllerian anomalies: role in sex determination in mammals. Reprod Fertil impact on therapy. AJR 167:1491–1495 Dev 7:713–722 Gassner I, Geley TE (2004) Ultrasound of female genital Lang IM, Babyn P, Oliver GD (1999) MR imaging of paediat- anomalies. Eur Radiol 14 [Suppl 4]:L107–L122 ric uterovaginal anomalies. Pediatr Radiol 29:163–170 Gharagozloo AM, Lebowitz RL (1994) Detection of poorly Lindsay AN, Voorhess ML, MacGillivary MH (1983) Multi- functioning malpositioned kidney with single ectopic cystic ovaries in primary hypothyroidism. Obstet Gyne- ureter in girls with urinary dribbling. AJR 164:957–961 col 61:433–437 Gilsanz V, Cleveland RH (1982) Duplication of the Müllerian MacGillivary MH, Morishimo A, Conte F, Grumbach M, ducts and genitourinary malformations. Part I: the value Smith EP (1998) Pediatric endocrinology update: an over- of excretory urography. Radiology 144:793–796 view. The essential roles of estrogens in pubertal growth, Gilsanz V, Cleveland RH, Reid BS (1982) Duplication of epiphyseal fusion and bone turnover: lessons from muta- the Müllerian ducts and genitourinary malformations. tions in the gene for aromatase and the estrogen receptor. Part II: analysis of malformations. Radiology 144:797– Horm Res 49:2–8 801 Marrakchi A, Belhaj L, Boussouf H, Chraibi A, Kadiri A Godfrey H, Abernethy L, Boothroyd A (1998) Torsion of (2005) Pure gonadal dysgenesis XX and XY: observations an ovarian cyst mimicking enteric duplication cyst on in 15 patients. Ann Endocrinol (Paris) 66:553–556 transabdominal ultrasound: two cases. Pediatr Radiol Marshall FF, Jeffs RD, Sarafyan WK (1979) Urogenital sinus 28:171–173 abnormalities in the female patient. J Urol 122:568–572

FOT2.indb 162 21.01.2008 14:06:30 Lower Urinary Tract Anomalies of Urogenital Sinus and Female Genital Anomalies 163

McLorie GA, Sheldon CA, Fleisher M, Churchill BM (1987) Silverman FN, Kuhn JP (1993) Caffey’s pediatric X-ray diag- The genitourinary system in patients with imperforate nosis: an integrated imaging approach, 9th edn. Mosby, anus. J Pediatr Surg 22:1100–1104 St Louis Merguerian PA, McLorie GA (1992) Disorders of the female Stephens FD (1983a) Normal embryology of the cloaca. In: genitalia In: Kelalis PP, King LR, Belman AB (eds) Clini- Stephens FD (ed) Congenital malformation of the urinary cal pediatric urology, 3rd edn. Saunders, Philadelphia, tract. Praeger, New York, pp 1–14 pp 1084–1105 Stephens FD (1983b) Abnormal embryology–cloacal dysgen- Metts JC, Kotkin L, Kasper S, Shyr Y, Adams MC, Brock JW esis. In: Stephens FD (ed) Congenital malformation of the (1997) Genital malformations and coexistent urinary urinary tract. Praeger,, New York, pp 15–52 tract or spinal anomalies in patients with imperforate Taybi H, Lachman RS (1996) Radiology of syndromes, meta- anus. J Urol 158:1298–1300 bolic disorders, and skeletal dysplasias, 4th edn. Mosby, Moore KL (1993) The developing human: Clinically oriented St Louis Embryology. W.B. Saunders Company, Harcourt Brace Teele RL, Share JC (1991) Ultrasonography of infants and Jovanovic, Philadelphia children. Saunders, Philadelphia, pp 240–244 Müller-Leisse C, Bick U, Paulussen K, Tröger J, Zachariou Teele RL, Share JC (1992) Ultrasonography of the female Z, Holzgreve W, Schumacher R, Horovitz A (1992) Ovar- pelvis in childhood and adolescence. Radiol Clin North ian cysts in the neonate-changes in sonographic pattern Am 30:743–758 in the follow-up and their management. Pediatr Radiol Teele RL, Share JC (1997) Transperineal sonography in chil- 22:395–400 dren. AJR 168:1263–1267 New MI (2003) Inborn errors of adrenal steroidogenesis. Mol Tokgoz H, Turksoy O, Boyacigil S, Sakman B, Yuksel E (2006) Cell Endocrinol 211:75–83 Complete androgen insensitivity syndrome: report of a Nidecker AC, Humphry A (1978) Peritoneal calcifi cation in case with solitary pelvic kidney. Acta Radiol 47:222–225 a neonate with imperforate hymen. J Can Assoc Radiol Tolete-Velcek F, Hansbrough F, Kugaczewski J, Coren CV, 29:277–279 Klotz DH, Price AF, Laungani G, Kottmeier PK (1989) Nievelstein RAJ, Van der Werff JFA, Verbeek FJ, Valk J, Ver- Uterovaginal malformations: a trap for the unsuspecting meij-Keers C (1998) Normal and abnormal embryonic surgeon. J Pediatr Surg 24:736–740 development of the anorectum in human embryos. Tera- Topaloglu AK, Vade A, Zeller WP (1997) Congenital adrenal tology 57:70–78 hyperplasia and bilateral ovarian cysts in a neonate. Clin Pellerito JS, McCarthy SM, Doyle MB, Glickman MG, DeCher- Pediatr 36:719–720 ney AH (1992) Diagnosis of uterine anomalies: relative Tourneux F (1888) Sur les premiers développements du cloa- accuracy of MR imaging, endovaginal sonography, and ques du tubercule génital et de l’anus chez l’embryon de hysterosalpingography. Radiology 183:795–800 mouton. J Anat 24:503–517 Pena A, Kessler O (1998) Posterior cloaca: a unique defect. Unsinn KM, Neu N, Krejci A, Posch A, Menardi G, Gassner I J Pediatr Surg 33:407–412 (1995) Pallister-Hall syndrome and McKusick-Kaufmann Rathke H (1882) Abhandlung zur Bildungsgeschichte der syndrome: one entity? J Med Genet 32:125–128 Tiere. Leipzig Van Bogaert LJ (1992) Surgical repair of hypospadias in Retterer E (1890) Sur l’origine et l’évolution de la région ano- women with symptoms of urethral syndrome. J Urol génitale des mammifères. J Anat Physiol 26:126–216 147:1263–1264 Rich MA, Brock WA, Pena A (1988) Spectrum of genitouri- Van der Putte SCJ (1986) Normal and abnormal development nary malformations in patients with imperforate anus. of the anorectum. J Pediatr Surg 24:434–440 Pediatr Surg Int 3:110–113 Wagner BJ, Woodward P (1994) Magnetic resonance evalu- Rieth KG, Comite F, Shawker TH, Cutler GB (1981) Pituitary ation of congenital uterine anomalies. Sem Ultrasound and ovarian abnormalities demonstrated by CT and CT MR 15:4–17 ultrasound in children with features of McCune-Albright Willi UV (1991) Pediatric genitourinary imaging. Curr Opin syndrome. Radiology 153:389–393 Radiol 3:936–945 Rosenberg HK, Sherman NH, Tarry WF, Duckett JW, McCrum Williams DJ, Bloomberg S (1976) Urogenital sinus in the Snyder H (1986) Mayer-Rokitansky-Kuster-Hauser syn- female child J Pediatr Surg 11:51–56 drome: US aid to diagnosis. Radiology 161:815–819 Wilson JD, Goldstein JL (1975) Classifi cation of hereditary Rosenblatt M, Rosenblatt R, Kutcher R, Coupey SM, Klein- disorders of sexual development. Birth Defects Orig Artic haus S (1991) Utero-vaginal hypoplasia. Pediatr Radiol Ser 11:1–16 21:536–537 Woolf RB, Allen WM (1953) Concomitant malformations: Rosenfeld DL, Lis E (1993) Gartner’s duct cyst with single the frequent simultaneous occurrence of congenital mal- vaginal ectopic ureter and associated renal dysplasia or formations of the reproductive and urinary tracts. Obstet agnesis. J Ultrasound Med 12:775–778 Gynecol 2:236–265 Shozu M, Akasofu K, Harda T, Kubota Y (1991) A new cause Wu A, Siegel MJ (1987) Sonography of pelvic masses in chil- of female pseudohermaphrodism: placental aromatase dren: diagnostic predictability. AJR 148:1199–1202 defi ciency. J Clin Endocrinol Metab 72:560–566 Ziereisen F, Guissard G, Damry N, Avni EF (2005) Sonogra- Siegel MJ (1995) Pediatric sonography, 2nd edn. Raven Press, phic imaging of the paediatric female pelvis. Eur Radiol New York, pp 441–442 15:1296–1309

FOT2.indb 163 21.01.2008 14:06:30