The etiology of ARM is unclear, but it is assumed to be multifactorial. In the animal models and human studies, genetic and environmental factors were identified. ARM have been induced in mice and rats by in utero exposure to Adriamycin, etretinate, and ethylenethiourea [4]. Some studies have suggested a link to in vitro fertilization [5] and maternal diabetes mellitus [6, 7]. No single gene or chromosomal locus has been identified. However, the frequent association with other congenital anomalies and genetic syndromes (Table 29.2) [8, 9] strongly supports a genetic component. Familial incidence has been shown in non-syndromic or isolated ARM, especially with the perineal and vestibular fistulas. Cloaca and rectoprostatic fistulae are less likely to have affected family members. The recurrence risk for rectovestibular and perineal fistulae is 3–4 % for full siblings and approximately 2 % for first-degree relatives [9].

The embryology of many congenital anomalies in humans is still not completely understood and recent studies are questioning the traditional theories. ARM is an example and several animal models have been developed to better characterize it.

Abnormal development of the cloaca rather than a persistent stage of normal embryology is the hypothesis for most of the ARM [4]. In the normal embryo, the cloaca is formed around the third week of gestation. It consists of a common cavity into which the hindgut (rectum), the allantois (bladder), and the mesonephric ducts (Wolffian) open cranially. Caudally, the cloaca ends as the tail gut. The cloacal membrane extends vertically and anteriorly from the allantois to the tail gut. As a result of the ventral growth of the genital tubercle, the shape of the cloaca changes and the cloacal membrane swings to a horizontal position. A urorectal fold (or urogenital septum) situated between the allantois and the hindgut descents caudally until it meets the cloacal membrane. This descent results in the separation of the urethra and the rectum and in the disintegration of the cloacal membrane at that area (seventh week of gestation). The dorsal cloaca in the tail region remains fixed and will constitute the anal orifice. In ARM animal models, unusual shape of the cloaca, too short cloacal membrane (absent dorsal parts), and abnormal junction between the proximal hindgut and the cloaca were found (Fig. 29.2).

The muscles surrounding the anorectum develop at the same time and are composed of three parts: the external sphincter, the puborectalis muscle , and the internal sphincter [10, 11]. The external sphincter appears first, followed by the puborectalis muscle which appears before 10 weeks of gestation and forms a sling around the anorectum. The internal sphincter grows after the rupture of the cloacal membrane and is not well differentiated until 10 weeks.

More than 50 % of the newborns with ARM have at least one associated anomaly [12]. The higher forms are even more likely to have more other anomalies. The severity of these associated anomalies is variable from incidental findings to life-threatening conditions. ARM can be part of a syndrome in 3.7 %, a chromosomal anomaly in 11 %, a sequence in 9 % (caudal dysplasia, Potter syndrome, prune belly), or the VACTERL association (vertebral defects, anal atresia, cardiac septal defects, esophageal atresia, renal anomalies, and radial limb defect) in 10 % [8]. Abdominal wall defects, especially omphalocele (OEIS complex: omphalocele, exstrophy, imperforate anus, and spine anomalies), can be associated with anal anomalies in 6.8 %. Associated affected systems include cardiovascular, gastrointestinal, spinal, sacral, vertebral, genitourinary, and gynecologic. Cardiovascular anomalies need to be ruled out before the surgical management because they are present in 16–22 % of patients with ARM [13, 14], and they can change the initial management if significant. The most frequent anomalies are atrial septal defect and ventricular septal defect, but more significant malformations such as tetralogy of Fallot, transposition of great vessels, and hypoplastic left heart syndrome are also possible. Many gastrointestinal anomalies have been described; the most frequent are tracheoesophageal in 10 % and duodenal with or without malrotation in 1–2 %. Hirschsprung disease is rare in patients with ARM, and the diagnosis must be confirmed with certitude because of the increased risk of fecal incontinence if proctectomy is performed in a context of ARM. Sacrovertebral anomalies are the most frequent bony structures defects (hemivertebrae, scoliosis, hemisacrum) and affect about a third of the patients [15]. The co-occurrence of sacral defect (typically hemisacrum), ARM, and presacral mass (teratoma or anterior meningocele) is known as the Currarino triad [16]. It is autosomal dominant with variable expressivity. Hypodevelopment of the sacrum can be quantified by the sacral ratio which is a helpful prognostic tool for continence and is associated with the severity of the ARM [17]. The prevalence of spinal anomalies is about 50 % [18] with a wide variety of severity (thickened filum, fibrolipoma, tethered cord, syringomyelia, myelomeningocele). The clinical significance of the occult spinal dysraphism is unclear, but routine detection is recommended in all types of ARM [15, 19]. Untethering of the cord improves the motor function in symptomatic patients, but it does not change the bowel or urinary function [20]. Patients with tethered cord have a worse functional prognosis that is also predictable by the type of ARM and sacral defect, but there is no evidence that prophylactic surgery can change the prognosis [21]. Close clinical follow-up and urodynamic studies are recommended in patients with tethered cord [18]. Genitourinary anomalies affect one third to half of patients [22]. Vesicoureteral reflux is the most frequent anomaly, affecting 60 % [23], followed by renal agenesis and dysplasia. In males, 20 % have cryptorchidism [24] and 5 % have hypospadias [22]. Patients with ARM associated with partial sacral agenesis are at increased risk of bladder-sphincter dysfunction and should be assessed by urodynamic studies [25]. Gynecologic anomalies have been unrecognized in the past but constitute a significant cause of morbidity on the long term [26]. In girls with rectovestibular fistula, 5 % have a vaginal septum and 9 % an absent vagina [27]. Hydrocolpos can cause a urinary obstruction or pyocolpos in the neonatal period. The absence or underdevelopment of the Mullerian structures can cause obstruction of the menstrual flow at the puberty.

A thorough physical examination is of critical importance and will often lead to the diagnosis of the ARM and the associated anomalies [28]. When inspecting the perineum, it is important to look at the color and aspect of the skin, assess the external sphincter contraction, and identify presence of ectopic anal opening. In boys, the presence of meconium at the meatus or in the urine will automatically confirm the presence of a rectourinary fistula. In girls, a single perineal orifice establishes the diagnostic of a cloaca. In this eventuality, it is mandatory to rule out hydrocolpos and urinary obstruction. In the cases where there is no visible meconium on physical examination, it is important to wait 24 h before labeling the type of anomaly and planning the surgical intervention. In the meantime, the baby should receive intravenous fluids, antibiotics, and nasogastric decompression. Associated anomalies must be ruled out by cardiac echography, renal and spinal ultrasound, and lumbar spine and sacrum plain radiographs. Within the first 24 h of life, if there is evacuation of meconium through a perineal fistula, a primary anoplasty can be performed. If the baby has other life-threatening issues, the fistula can be dilated and the definitive surgical treatment postponed for a few months as long as the rectum is well decompressed. If after 24 h there is no evidence of meconium in the urine or through a perineal fistula, a cross-table lateral radiograph can be performed with the baby in prone position and a marker at the suspected site of the external sphincter in order to assess the level of the rectal gas compared to the pubococcygeal line. A perineal ultrasound can also be performed. A distance between the distal rectal pouch and the perineum greater than 15 mm suggests an intermediate or high ARM [29].

Modern surgical techniques and neonatal care have improved the outcomes of all the congenital malformations and ARM are not an exception. Mortality of patients with ARM had been between 10 and 20 % and has decreased to 3 % more recently. It is principally due to the severe associated anomalies. The mortality is about three times higher in patients with high anomalies than in patients with low anomalies [3].