One Hundred Three Consecutive Patients with Anorectal Malformations and Their Associated Anomalies

ARTICLE One Hundred Three Consecutive Patients With Anorectal Malformations and Their Associated Anomalies

Sechin Cho, MD; Shawn P. Moore, MD; Tony Fangman, MD

Objective: A long-term retrospective analysis of 103 in- Results: The incidence of ARMs in our study was ap- fants with anorectal malformations (ARMs) was con- proximately 1 in 2500 live births. Additional anomalies ducted to describe any associated congenital anomalies were found in 71% of infants with ARMs. Associated and surgical classifications. anomalies by major organ system included genitourinary anomalies (49%), musculoskeletal anomalies (43%), Design: Retrospective medical record review. craniofacial anomalies (34%), cardiovascular anomalies (27%), gastrointestinal anomalies (18%), respiratory Setting: This case series was conducted on all infants anomalies (13%), and central nervous system anoma- with ARMs born at, or referred to, any of 3 major lies (12%). The most common chromosomal abnormali- medical centers in Wichita, Kan, for close to a 22-year ties were trisomies (8%), and ARMs were associated with period. VATER complex (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and Patients: The 103 infants in this study represent a con- renal anomalies) in 11 cases (11%) and VACTERL (ver- secutive sample of patients with ARMs. Patients were sepa- tebral, anal, cardiac, tracheal, esophageal, renal, and limb rated into 2 groups: isolated ARMs without associated anomalies) in 4 cases (4%). anomalies (n=30), and ARMs with associated anomalies (n=73). The male-female ratio was 2:1. Conclusions: Patients with ARMs have a high incidence of associated congenital anomalies. Evaluation of Main Outcome Measures: Patients with associated the most commonly affected organ systems in these in- anomalies were further classified into groups of ARMs fants is essential because it is these associated anomalies with minor anomalies; major anomalies; chromosomal that account for most of the morbidity and mortality that abnormalities; and malformation syndromes, associa- is associated with this condition. tions, or sequences. Only anomalies that occurred more than once were reported. Malformations were also classified according to major organ systems. Arch Pediatr Adolesc Med. 2001;155:587-591

HE INCIDENCE of anorectal RESULTS malformations (ARMs) var- ies from 1 in 1500 to 1 in INCIDENCE AND DEMOGRAPHICS 5000 live births.1-5 The surgical and medical manage- In our patient population, the incidence mentT of patients with these malformations of ARMs was approximately 1 in 2500 can be complex, especially when one con- based on all infants born at Wesley Med- siders the high frequency of concomitant ical Center from January 1, 1975, to anomalies that occur with ARMs. This fre- October 16, 1996. During this time pe- quency of additional anomalies in patients riod, there were 43 births with ARMs of with ARMs ranges from 40% to70%.1,2,4,5 106 012 total births at this hospital. Sex Thorough evaluation of patients with distribution of all 103 patients with ARMs ARMs is essential because it is these was 67% male (n=69) and 33% female coexisting anomalies that account for (n=34). The racial composition of these most of the morbidity and mortality that patients was 85% white, 5% African Ameri- is associated with this condition.3,6-8 This can, and 10% Hispanic and other. The av- article addresses the surgical classifica- erage maternal age was 25.8 years (age From the Department of tion and description of additional range, 15-40 years). Karyotypes were ob- Pediatrics, Kansas University anomalies that occurred in a consecutive tained for 39% of the infants (n=40), and School of Medicine–Wichita. series of 103 patients with ARMs. 25% of these findings were abnormal.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Table 1. Wingspread Surgical Classification of Patients PATIENTS AND METHODS With Anorectal Malformations*

Classification Male Female This study encompassed all infants with ARMs who High 40 (58) 9 (27) were born at, or referred to, any of 3 major medical AA with rectoprostatic urethral fistula −23 −7† centers in Wichita, Kan, from January 1, 1975, to Oc- AA without fistula −15 −1 tober 16, 1996. Medical records of 103 patients were Rectal atresia −2 −1 reviewed retrospectively at these 3 hospitals (Wes- Intermediate 3 (4) 10 (29) ley Medical Center, St Joseph Medical Center, and Rectobulbarurethral fistula −1 −1‡ St Francis Regional Medical Center) for all infants ad- −5§ mitted during this time period with a diagnosis of ano- Anal agenesis without fistula −2 −4 rectal anomalies, anal stenosis, or imperforate anus. Low 23 (33) 13 (38) Data that was recorded included date of birth, sex, Anocutaneous fistula −13 −4 race, maternal age, county and hospital of birth, sur- −1࿣ gical classification, karyotype results, and any asso- Anal stenosis −10 −8 ciated anomalies. Associated anomalies were only re- Cloaca N/A 1 (3) ported in the results if they were observed more than Rare malformations 1 (1.4) 0 once (in more than one individual). Unspecified 2 (2.9) 1 (3) Surgical classification of ARMs was conducted Total 69 34 in accordance with the Wingspread classification, and anomalies were divided into low, intermediate, high, *AA indicates anorectal agenesis; N/A, not applicable. Values are given as 9 numbers (percentages), except where indicated. Percentages indicate cloaca, or rare malformations. Clinical geneticists percent of total males and females in each category. (S.C.) were consulted in every case, and karyotypes †Anorectal agenesis with rectovaginal fistula. were obtained to confirm chromosomal abnormali- ‡Rectovestibular fistula. ties when suspected on physical examination (n=40) §Rectovaginal fistula. by these geneticists. Other diagnostic procedures were ࿣Anovestibular fistula. also performed when clinically indicated. Incidence rates for ARMs were calculated for infants born at Wesley Medical Center during the study period. Other tem, which were seen in 50 (49%) of the infants with anomalies that were associated with ARMs were docu- ARMs. Other organ systems with anomalies included the mented and classified under major organ systems. Rec- musculoskeletal (44 [43%]), craniofacial (35 [34%]), car- ognizable anomaly patterns were also classified into diovascular (28 [27%]), gastrointestinal (19 [18%]), res- malformation syndromes, malformation associa- piratory (13 [13%]), and central nervous system (12 tions, malformation sequences, and chromosomal ab- [12%]). Tracheoesophageal fistulas were included un- normalities whenever appropriate. Major anomalies were defined as those that have serious medical, sur- der gastrointestinal anomalies. Patent ductus arteriosus gical, or cosmetic consequences, whereas minor and patent foramen ovale were not included in the car- anomalies did not have these implications. Statisti- diovascular anomalies because they are common physical analysis consisted of ␹2 tests conducted with SPSS ologic phenomena in premature infants. Other minor software version 9.0 (SPSS Inc, Chicago, Ill). anomalies, including ectodermal skin defects, webbed neck, and Simian creases, were observed in 13% of the infants. Table 2 gives the most commonly observed additional anomalies by organ system. WINGSPREAD SURGICAL CLASSIFICATION CLASSIFICATION OF ADDITIONAL ANOMALIES Surgical classification of the ARMs was performed according to the Wingspread classification.9 The results of All 73 patients with additional anomalies were then clas- this classification broken down by sex are presented in sified into 1 of 6 categories: (1) malformation syn- Table 1. A high ARM was found in 58% of males and dromes, (2) malformation associations, (3) malforma- only 27% of females. Intermediate ARMs were found in tion sequences, (4) chromosomal abnormalities, and those 4% of males and 29% of females. Low ARMs were ob- with (5) major anomalies or (6) minor anomalies. There served in 33% and 38% of males and females, respec- were 16 patients (11 males, 5 females) with minor anoma- tively. Rare malformations occurred in only 1% of males lies who could not be accounted for by a syndrome, se- and 3% of females. There was 1 female with a cloaca mal- quence, etc. Major anomalies were observed in 27 pa- formation. The Wingspread surgical classifications of all tients who also did not conform to another diagnostic infants are presented in Table 1. category. Chromosomal abnormalities were observed in 10 patients (10%). Eight of these patients had trisomies ASSOCIATED ANOMALIES BY ORGAN SYSTEM (chromosomes 21, 18, 13); 1 had a ring chromosome 13; and 1 had a derivative chromosome 22. Overall, karyo- Anomalies that were associated with ARMs were re- types were obtained for 40 patients, and 10 of these were ported by classification into major organ systems abnormal (25%). Malformation syndromes were ob- (Table 2). Overall, 73 (71%) of 103 infants with ARMs served in 3 patients (3%), and these consisted of cat’s- had other associated anomalies. The most commonly ob- eye syndrome, Opitz syndrome, and Potter syndrome type served anomalies were those of the genitourinary sys- I. Malformation associations occurred in 15 patients

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Table 2. Most Frequently Observed Table 3. Classification of Patients Additional Anomalies by Organ System* With Additional Anomalies

Frequency, Anomaly, No. Male Female Total Organ System Anomaly No. (%) Minor anomalies 11 5 16 Isolated ARM 30 (29) Major anomalies* 18 9 27 Genitourinary 50 (49) Malformation syndromes 2 1 3 Renal agenesis 9 (9) Cat’s-eye syndrome −1 Ambiguous genitalia 7 (7) Opitz syndrome −1 Multicystic dysplastic kidney 6 (6) Potter syndrome type I −1 Cryptorchidism 5 (5) Malformation associations 10 5 15 Bifid scrotum 4 (4) VATER complex† −8 −3 Musculoskeletal 44 (43) VACTERL‡ −2 −2 Hemivertebra 7 (7) Malformation sequences 1 1 2 Micrognathia 7 (7) Caudal regression sequence −1 −1 Dislocated hip 5 (5) Chromosomal abnormalities 7 3 10 Abnormal rib number 4 (4) Trisomy 21 −4 Polydactyly 4 (4) Trisomy 18 −2 −1 Omphalocele 3 (3) Trisomy 13 −1 Craniofacial 35 (34) 47, XY, +der (22) mat −1 Low-set ears 15 (15) 46, XX, r(13) −1 Simian crease 7 (7) Total 49 24 73 Potter facies 6 (6) Epicanthal folds 5 (5) *Defined as those that had serious medical, surgical, or cosmetic Cleft palate 5 (5) consequences, whereas minor anomalies did not. Cardiovascular 28 (27) †VATER indicates vertebral defects, anal atresia, tracheoesophageal fistula VSD 13 (13) with esophageal atresia, and radial and renal anomalies. ASD 8 (8) ‡VATER indicates vertebral, anal, cardiac, tracheal, esophageal, renal, and Pulmonary stenosis 5 (5) limb anomalies. Tetralogy of Fallot 3 (3) Dextrocardia 3 (3) CLASSIFICATION OF ASSOCIATED ANOMALIES Gastrointestinal 19 (18) BY WINGSPREAD SURGICAL CLASSIFICATION TE fistula 11 (11) Esophageal atresia 10 (10) The 6 categories of malformation classification were also Duodenal atresia 4 (4) compared with the Wingspread surgical classifications Malrotation 1 (1) 2 Respiratory 13 (13) of these patients (Table 4). Results of ␹ analysis indi- Hypoplastic lungs 10 (10) cated that patients with major anomalies associated with Diaphragmatic hernia 3 (3) ARMs were 16.5 times more likely to have a high surgi- Choanal atresia 2 (2) cal ARM than patients with isolated ARMs (PϽ.001). Pa- Subglottic stenosis 1 (1) tients with minor anomalies were also 8 times more likely CNS 12 (12) to have high lesions than patients with isolated ARMs Meningomyelocele 2 (2) Cerebral atrophy 2 (2) (PϽ.002). Males were more likely to have high lesions Teratoma 1 (1) than females; however, this was not statistically signifi- Aqueductal stenosis 1 (1) cant (PϽ.065). Overall, patients with additional anoma- Microcephaly 1 (1) lies were also more likely to have high lesions than patients with isolated ARMs, and the reverse was true for *ARM indicates anorectal malformation; VSD, ventricular septal defect; low lesions (odds ratio, 13.8; PϽ.001). ASD, atrial septal defect; TE, tracheoesophageal; and CNS, central nervous system. Percentages represent fraction of total number of infants (N = 103) with anomalies in each organ system category. COMMENT Anorectal malformations are relatively common congen- (15%), 11 of which were VATER complex (vertebral de- ital anomalies. The incidence of ARMs was approxi- fects, anal atresia, tracheoesophageal fistula with esoph- mately 1 in 2500 live births in our patient population, ageal atresia, and radial and renal anomalies) and 4 of which is within the reported incidence range in the lit- which were VACTERL (vertebral, anal, cardiac, tra- erature.1-5 It is well known that additional congenital cheal, esophageal, renal, and limb anomalies). Karyo- anomalies are often present in patients with ARMs, and types were obtained for 11 of the infants with malfor- it is these coexisting anomalies that account for the high mation associations, and all findings were normal. morbidity and mortality associated with this condition.2-4,6 Malformation sequences were observed in only 2 pa- We observed additional congenital anomalies in 71% of tients, and both consisted of caudal regression se- infants affected with ARMs in our population, which is quence. Overall, 30 of 73 patients with additional anoma- slightly higher than the 30% to 70% incidence of addi- lies had defined chromosomal abnormalities or tional anomalies reported in the literature.1,2,4,5,10 Differ- malformation syndromes, associations, or sequences. ences in the percentages of additional anomalies that are These 6 categories and their breakdown by patient sex observed can be attributed to how exhaustively each pa- are presented in Table 3. tient was evaluated in these studies, as well as by ac-

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Classification

Rare Anomaly, No. Low Intermediate High Cloaca Malformation Unspecified Total Isolated ARM 22 3 5 0 0 0 30 Minor anomalies 5 1 10 0 0 0 16 Major anomalies 4 5 15 1 1 2 28 Malformation syndromes 2 0 1 0 0 0 3 Malformation associations 1 1 12 0 0 1 15 Malformation sequences 1 0 1 0 0 0 2 Chromosomal abnormalities 1 3 5 0 0 0 9 Total 36 13 49 1 1 3 103

*ARM indicates anorectal malformation.

cess and utilization of radiological modalities, such as mag- individuals with ARMs and any associated malforma- netic resonance imaging (MRI) and ultrasound. The male- tions to investigate possible chromosomal abnormalities. female ratio in this population was approximately 2:1, In a limited literature review, several syndromes were which is greater than the reported range of 1.2:1 to 1.8:1 associated with ARMs, including Townes-Brocks, Johanson- in more recent studies.2-4,10 Additionally, high ARMs were Blizzard, Pallister-Hall, Currarino, cat’s-eye, Down, Opitz, more common in males than females bya4to1ratio. deletion 13q, Zellweger, and FG syndromes.4,5,10,20-23 Mal- The most common organ system that was affected by formation associations were observed in 15 patients and additional anomalies was the genitourinary system. Ab- consisted of 11 cases of VATER and 4 cases of VACTERL. normalities in the genitourinary system were observed in The expression of these 2 malformation associations shows 49% of patients with ARMs. Other case series describe simi- phenotypic heterogeneity; however, we defined patients lar results, with the frequency of genitourinary anoma- with VATER or VACTERL as having 3 or more of the lies ranging anywhere from 26% to 59% in patients with anomalies that are associated with these condi- ARMs.1,3,4,11-14 Therefore, thorough evaluation of the geni- tions.4,5,12,24-26 Other malformation associations and se- tourinary system in patients with ARMs is essential. Most quences that are associated with ARMs include exstrophy authorities recommend a vesicoureterogram voiding cys- of cloaca sequence, sirenomelia sequence, caudal regres- tourethrogram and ultrasound to study the kidneys and sion sequence, Klippel-Feil sequence, OEIS complex (om- bladder in all patients with ARMs.3,8,11-14 Musculoskeletal phalocele, exstrophy, imperforate anus, spinal defects), and anomalies were observed in 43% of the infants in this case CHARGE (coloboma [of eyes], hearing deficit, choanal atre- series. The reported range of musculoskeletal anomalies sia, retardation of growth, genital defects [males only], and in patients with ARMs is 15% to 44%.3,4,7,12,13 Findings from endocardial cushion defect) association.4,5,22 physical examination can reveal many of these anomalies It is well established that high ARMs are more com- in the periphery, and various radiological modalities should mon in males than females and are also more frequently be employed to evaluate the lumbosacral spine. Many au- associated with other congenital anomalies than low le- thorities recommend ultrasonography and radiography, sions.1-4,10 In our study, high ARMs were observed in 58% and the spine can also be evaluated during the voiding of males (n=40) and 27% of females (n=9). Results of ␹2 study, with MRI reserved only for abnormal findings on analysis indicated that patients with ARMs and additional radiographs or ultrasound.3,12,14,15 Others recommend an anomalies were 13 times more likely to have high lesions MRI in all patients with ARMs.16,17 At our institution, we than patients with isolated ARMs (PϽ.001). This is in line use ultrasonography as a screening tool for lumbosacral with contemporary thought that high ARMs are more com- anomalies in patients with ARMs with MRI reserved for plex lesions that are more likely to be accompanied by abnormal findings on ultrasound, as the role of MRI and anomalies in other organ systems also forming between ges- ultrasound has not been definitively established in in- tational weeks 4 and 8 due to some teratogenic event.5 fants with ARMs.18 Anorectal malformations are relatively common con- Cardiovascular anomalies were observed in 27% of genital anomalies that are frequently associated with other the infants in this case series, and we performed screen- congenital anomalies. It is these associated anomalies that ing echocardiograms on all patients with ARMs owing to account for most of the morbidity and mortality that is the frequency of these lesions.3,7,12,19 We also observed a associated with ARMs. Therefore, a thorough evalua- high incidence of craniofacial, gastrointestinal, respira- tion of infants born with ARMs is warranted to mini- tory, and central nervous system anomalies in this case se- mize these complications. ries. In addition, 29% of the infants had notable chromosomal abnormalities or malformation syndromes, Accepted for publication November 17, 2000. associations, or sequences. The most common chromo- Corresponding author and reprints: Sechin Cho, MD, somal abnormality was trisomy 21, and the association be- Department of Pediatrics, Kansas University School of tween Down syndrome and ARMs has been well de- Medicine–Wichita, 1010 N Kansas St, Wichita, KS 67214 scribed.10,20,21 Obtaining karyotypes is warranted on (e-mail: [email protected]).

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