201 10 Persistent Cloaca – Clinical Aspects Alexander M. Holschneider and Horst Scharbatke Contents In contrast, the cloacal membrane is always too short in abnormal rodent embryos and the region of the 10.1 Introduction . 201 future anal opening is missing, in contrast to normal 10.2 General Clinical Aspects . 201 mouse embryos (see Chap. 4 for a detailed descrip- 10.3 Classification of Persistent Cloacas . 202 tion) [5]. 10.3.1 The Perineum . 202 Several experimental models of ARM including 10.3.2 UGS Variations . 202 persistent cloaca exist. They are based on the terato- 10.3.3 Vaginal Variations . 202 genic effect of ethylenethiourea in the rat [6] and ex- 10.3.4 Rectal Variations . 202 10.4 Associated Malformations . 203 posure of rat fetuses to adriamycin [7] or etretinate, a 10.5 Initial Management of the Newborn . 207 long-acting vitamin A analog, in mice [8]. 10.5.1 Diagnostic Management . 207 A molecular basis for ARM was first shown by References . 208 Kimmel et al. [9]. In the murine model of ARM; Gli3-/-mutants exhibited anal stenosis and ectopic anus, Gli2-/-mutants exhibited imperforate anus and rectourethral fistula, and Gli2-/-Gli3+/- mutants de- veloped a cloacal abnormality. In addition, isochro- 10.1 Introduction mosome 18q has been shown to cause megacystis, intrauterine growth retardation, and cloacal dysgen- Persistent cloaca represents the most complex de- esis sequence in a fetus [10]. Keppler-Noreuil [11] formity in female anorectal, vaginal, and urogenital suggests a possible etiologic role for homeobox genes, malformations. It is defined as a defect in which the such as HLXB9, with mutations resulting in ARM rectum, one or two vaginas and the urinary tract con- and spinal abnormalities. verge into one common channel. It is very rare and occurs in 1:250,000 newborns [1]. It is physiological in some reptiles, birds, and a few mammals. In hu- 10.2 General Clinical Aspects mans, however, it represents a malformation that oc- curs at a very early stage of development. Prenatal diagnosis of persistent cloaca has been re- According to Qi et al. [2] and Nievenstein et al. ported, but is not always accurate [12,13]. In contrast, [3], the rat tail gut immediately distal to the hindgut clinical diagnosis is simple. In girls, a single opening starts to regress by apoptosis on day 12 of gestation on the perineum is always suspicious of a cloacal mal- in a craniocaudal direction and has regressed com- formation. The length of the introitus is characteristi- pletely by day 13.5. This tail-gut regression and the cally shorter than in a normal girl. Cloacas have only urorectal septum play an important role in the pro- rarely been reported in boys in whom the urethra and cess of cloacal separation by cellular proliferation and rectum has coalesced into a common channel that is differentiation. Rupture of the anal membrane plays connected to the external surface in the perineal or an additional role. Cloacal malformations, accord- anal area [14]. In girls, an abdominal mass and se- ing to these authors, are early defects, while anorectal vere abdominal distension resulting from hydrome- malformations (ARM) with the anus in the normal trocolpos and/or rectal obstruction can frequently position are late embryonic defects. However, in the be observed. Additional malformations of the lower opinion of Kluth and Lambrecht [4], the embryonic limbs, genitalia, skin (hemangioma), urogenital tract, cloaca never passes through a stage that is similar to vertebral, cardiac, and gastrointestinal deformities, any form of ARM in neonates, including the cloaca. among others may occur. A rarity is the posterior clo- 202 Alexander M. Holschneider and H. Scharbatke aca, described first by Peña and Kessler [15]. In these can be observed at the tip of the phallus in addition patients the vagina and urethra fuse together but the to the proximal urethra fusing with the UGS. The urogenital sinus (UGS) opens into the anterior rectal perineal skin can be covered by a hemangioma and wall; the rectum is normal or minimally mislocated abnormal pigmentation (Fig. 10.1 A–F). anteriorly. The most severe type of deformity is cloa- cal exstrophy, a combination of cloaca with blad- der exstrophy that was first reported by Rickham in 10.3.2 UGS Variations 1960 [16]. It is now called vesicointestinal fissure (see Chap. 14 for details). The UGS may exhibit an ending on the tip of the cli- toris, a subclitoral meatus, a wide opening to a short common channel, or a long sinus with the junction 10.3 Classification of urethra, vagina(s), and rectum above the pubococ- of Persistent Cloacas cygeal (PC) line. By using this anatomical projection of the upper border of the prostate and the ischial (I) A detailed description of the varying anatomy of cloa- point representing the plane of the upper border of cal malformations has been published by Hendren [1, the internal anal sphincter, high, intermediate, and 17–22] and Peña [23–25]. Hendren distinguishes be- low types of cloaca can be distinguished according tween anomalies of the perineum, UGS, vagina, and to the Wingspread classification of ARM [26]. How- rectum (Table 10.1). ever, there are so many variations of anomalies of the vagina, urethra, and rectum in cloacae that this clas- sification, which is very useful in ARM, is not very Table 10.1 Classification of cloacal malformations. UGS uro- helpful for the classification of cloacae. Peña’s sacral genital sinus, PC pubococcygeal ratio [25], which should be in 0.77 in normal children, Type Anomaly gives an idea of sacral hypodevelopment and, there- fore, the probable degree of neurogenic bladder dys- Type I: Forme fruste Anteposition of anus with ultra short UGS and normal female genitalia function and disturbed bowel control, but is no clas- sification. Nevertheless, it is important to distinguish Type II: Low cloacal Short UGS < 3 cm (confluence between high and low cloacal deformities because, for malformation below PC line) example, a UGS less than 3 cm long can be treated by Type III: High cloacal long UGS > 3 cm (confluence total UGS advancement, whereas in longer channels malformation at or above PC line) an abdominal approach is necessary (Fig. 10.2) [27]. Type IV: Vagina and/or rectum into bladder cavity Rare cloacal Posterior cloaca in boys 10.3.3 Vaginal Variations malformations Cloacal exstrophy The two most common variations are a single vaginal opening in the upper urethra, with the rectal opening below this orifice, and a double side-by-side vagina 10.3.1 The Perineum with the rectum ending on the septum between both vaginas. In cases of hemivaginas and an incomplete According to Hendren [1] there is a wide range of septum, the rectal fistula can be situated high on deformities of each pelvic structure. At the mild end the septum; in cases with two separated vaginas it of the spectrum of perineal malformations there is can usually be found between the vaginal openings. an almost normal-looking vaginal opening with an There might be two vaginas but atresia, or even ab- anal orifice that is situated very close, but not incor- sence of one, double diverging vaginas, two separate porated into, the UGS. In the next degree the vagi- vaginas, or both, or two vaginas entering the bladder nal introitus might be incompletely formed and the (Fig. 10.3 A–G). anus displaced forward with a dysplastic perineum between both openings. There might be a large sinus urogenitalis opening and the anal opening just be- 10.3.4 Rectal Variations hind it, or a single perineal opening covered by the clitoris, which could be either hyper- or hypoplastic. The rectum can enter the UGS separate from and be- In a very few cases an accessory hypoplastic urethra low the vagina, may enter the posterior wall of the 10 Persistent Cloaca – Clinical Aspects 203 Fig. 10.1 Clinical aspects of cloacal malformations. A Almost D Malformation of the labia majora. E Total malformation of normal-looking female genitalia. B Enlarged labia majora. C the introitus; the labia majora are visible. F Labia majora not Male aspect of female genitalia (after drainage of hydrocolpos). developed vagina or the bladder, it can be positioned between 10.4 Associated Malformations and anterior to two vaginal openings, or run as a long fistula all along the posterior wall of the vagina down Being a very complex deformity of a very early stage to the UGS. The rectal pouch at the upper end of the of human development, many associated anomalies fistula is very high up in these cases, sometimes even can be observed in patients with cloacal malforma- above the peritoneal reflection (Fig. 10.4). tions (Table 10.2). 204 Alexander M. Holschneider and H. Scharbatke Table 10.2 Vesicoureteral reflux Absence of uterus Some of the associ- ated anomalies found in children Malformations of the kidneys Bladder exstrophy with cloacal anomalies Tethered cord Gastrointestinal duplications Neurogenic Bladder Pouch colon Diastematomyelia Cardiac malformations Myelomeningocele Vertebral deformities Lower-limb deformities Esophageal atresia Occluded tubes Cerebral anomalies Absence of one ovary Abnormalities of the enteric nervous Hypoplastic labia Fig. 10.2 Urogenital sinus (UGS) variations [modified ac- cording to Hendren (1992) J Pediatr Surg 27:890–901, Fig. 3]. a Long UGS ending in the tip of the clitoris. b Subclitoral me- atus. c Wide opening of the UGS (like a vagina). d With acces- sory tract 10 Persistent Cloaca – Clinical Aspects 205 Fig. 10.3 Vaginal variations [modified according to Hendren (1992) J Pediatr Surg 27:890–901, Fig. 4]. a Double vagina, side by side. b Double vagina, but atresia of one.