Amelia: a multi-center descriptive epidemiologic study in a large dataset from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature

This study describes the epidemiology of congenital amelia (absence of limb/s), using the largest series of cases known to date. Data were gathered by 20 surveillance programs on congenital anomalies, all International Clearinghouse for Birth Defects Surveillance and Research members, from all continents but Africa, from 1968 to 2006, depending on the program. Reported clinical information on cases was thoroughly reviewed to identify those strictly meeting the definition of amelia. Those with amniotic bands or limb-body wall complex were excluded. The primary epidemiological analyses focused on isolated cases and those with multiple congenital anomalies (MCA). A total of 326 amelia cases were ascertained among 23,110,591 live births, stillbirths and (for some programs) elective terminations of pregnancy for fetal anomalies. The overall total prevalence was 1.41 per 100,000 (95% confidence interval: 1.26-1.57). Only China Beijing and Mexico RYVEMCE had total prevalences, which were significantly higher than this overall total prevalence. Some under-registration could influence the total prevalence in some programs. Liveborn cases represented 54.6% of total. Among monomelic cases (representing 65.2% of nonsyndromic amelia cases), both sides were equally involved, and the upper limbs (53.9%) were slightly more frequently affected. One of the most interesting findings was a higher prevalence of amelia among offspring of mothers younger than 20 years. Sixty-nine percent of the cases had MCA or syndromes. The most frequent defects associated with amelia were other types of musculoskeletal defects, intestinal, some renal and genital defects, oral clefts, defects of cardiac septa, and anencephaly.     

Associated anomalies in cases with agenesis of the corpus callosum

Agenesis of corpus callosum (ACC) is an uncommon congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with ACC often have other non‐ACC associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with ACC were collected in all live births, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population‐based registry of congenital malformations. Of the 99 cases with ACC, representing a prevalence of 2.56 per 10,000, 73 (73.7%) had associated anomalies. There were 16 (16.2%) cases with chromosomal abnormalities, and 13 (13.2%) nonchromosomal recognized dysmorphic conditions including syndromes two each: Aicardi, Dandy–Walker, and fetal alcoholism. Forty‐four (44.4%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the urogenital, the central nervous, the cardiovascular, and the digestive systems were the most common other anomalies in the cases with MCA. The anomalies associated with ACC could be classified into a recognizable malformation syndrome in 29 out of the 73 cases (39.7%) with associated anomalies. This study included special strengths: it is population‐based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, three of four cases, emphasizes the need for a screening for other anomalies in cases with ACC.     

Associated anomalies in Pierre Robin sequence

Pierre Robin sequence (PRS) is frequently co-occurring with other non-PRS congenital anomalies. The types and the prevalence of anomalies co-occurring with PRS vary in the reported studies. The aims of this report was to study the types and the prevalence of the anomalies co-occurring with PRS in a well-studied population northeastern France. The types and the prevalence of anomalies co-occurring in cases with PRS were ascertained in all terminations of pregnancy, stillbirths and live births in 387,067 births occurring consecutively during the period 1979–2007 in the area covered by our registry of congenital anomalies which is population-based, 89 cases of PRS were registered during the study period with a prevalence of 2.29 per 10,000 births, 69.7% of the cases had associated non-PRS anomalies. Chromosomal abnormalities were present in 10 (11.2%) cases including three 22 q11.2 deletion. Non-chromosomal recognizable conditions were diagnosed in 27 cases (30.3%) including 10 Stickler syndrome, 8 Treacher Collins syndrome, 3 cases with short stature and 6 other syndromes. Multiple congenital anomalies (MCA) were present in 25 cases (28.1%). The most frequent MCA were in the ear, face and neck (35 out of 98 anomalies, 35.7%), cardiovascular (18 anomalies, 18.4%), musculoskeletal (11 anomalies, 11.2%), central nervous (7 anomalies, 7.1%), urinary (6 anomalies, 6.1%), and eye (6 anomalies, 6.1%) system. The high prevalence of associated anomalies justifies a thorough screening for other congenital anomalies in cases with PRS.     

Associated anomalies in cases with congenital clubfoot

Congenital clubfoot CTEV is a common congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with CTEV often have other non‐CTEV associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with CTEV were collected in all livebirths, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population‐based registry of congenital malformations. Of the 504 cases with CTEV, representing a prevalence of 13.02 per 10,000, 107 (21.2%) had associated anomalies. There were 31 (6.1%) cases with chromosomal abnormalities, and 21 (4.2%) non‐chromosomal recognized dysmorphic conditions including syndromes: 6 arthrogryposis multiplex congenita, 2 22q11.2 microdeletion, and one fetal alcohol syndrome. Fifty‐five (10.9%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the cardiovascular, the central nervous, the urinary, the orofacial, and the musculoskeletal systems were the most common other anomalies in the cases with MCA. The anomalies associated with CTEV could be classified into a recognizable malformation syndrome in 52 of the 107 cases (48.6%) with associated anomalies. This study included special strengths: it is population‐based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, one of five cases, emphasizes the need for a screening for other anomalies in cases with CTEV.     

Associated anomalies in cases with achondroplasia

Associated congenital anomalies may be observed in cases with achondroplasia. The prevalence reported in the literature and the types of co-occurring congenital anomalies are variable between the reported studies. The aim of this study was to establish the prevalence and to describe the associated anomalies in cases with achondroplasia. This study included 25 cases ascertained from our registry of congenital anomalies including all terminations of pregnancy, stillbirths and live births between 1979 and 2007 in 387,067 consecutive births (the prevalence of achondroplasia was 6.4 per 100,000 births), and 223 cases ascertained from the French Little People organization built on the model of LPA (Little People of America, Inc.). Out of these 248 cases of achondroplasia 37 (14.9%) had associated anomalies including 4 (1.6%) cases with chromosomal abnormalities (2 trisomies 21, one 22 q11.2 deletion, and one 47, XXX), 2 (0.8%) cases with recognizable non-chromosomal conditions (one Moebius syndrome and one Pierre Robin sequence) and 31(12.5%) cases with MCA (multiple congenital anomalies). The 31 cases with MCA had 45 anomalies. Anomalies in the urogenital system (24.4%), the cardiovascular system (20.0%), the musculoskeletal system (15.5%), the central nervous system (11.1%), the eye (11.1%), and the orofacial system (8.8%) were the most common MCA. The overall prevalence of associated anomalies shows that the individuals with achondroplasia need a careful screening for other congenital anomalies.     

Gastroschisis and associated defects: an international study

Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.     

Amniotic band syndrome and limb body wall complex in Europe 1980–2019

Amniotic band syndrome (ABS) and limb body wall complex (LBWC) have an overlapping phenotype of multiple congenital anomalies and their etiology is unknown. We aimed to determine the prevalence of ABS and LBWC in Europe from 1980 to 2019 and to describe the spectrum of congenital anomalies. In addition, we investigated maternal age and multiple birth as possible risk factors for the occurrence of ABS and LBWC. We used data from the European surveillance of congenital anomalies (EUROCAT) network including data from 30 registries over 1980–2019. We included all pregnancy outcomes, including live births, stillbirths, and terminations of pregnancy for fetal anomalies. ABS and LBWC cases were extracted from the central EUROCAT database using coding information responses from the registries. In total, 866 ABS cases and 451 LBWC cases were included in this study. The mean prevalence was 0.53/10,000 births for ABS and 0.34/10,000 births for LBWC during the 40 years. Prevalence of both ABS and LBWC was lower in the 1980s and higher in the United Kingdom. Limb anomalies and neural tube defects were commonly seen in ABS, whereas in LBWC abdominal and thoracic wall defects and limb anomalies were most prevalent. Twinning was confirmed as a risk factor for both ABS and LBWC. This study includes the largest cohort of ABS and LBWC cases ever reported over a large time period using standardized EUROCAT data. Prevalence, clinical characteristics, and the phenotypic spectrum are described, and twinning is confirmed as a risk factor.     

Associated anomalies in multi-malformed infants with cleft lip and palate: An epidemiologic study of nearly 6 million births in 23 EUROCAT registries

We studied 5,449 cases of cleft lip (CL) with or without cleft palate (CL/P) identified between 1980 and 2000 from the EUROCAT network of 23 registers (nearly 6 million births) in 14 European countries. We investigated specific types of defects associated with clefts. Among CL/P cases (prevalence = 9.1 per 10,000), 1,996 (36.6%) affected only the lip (CL) and 3,453 (63.4%) involved CL and palate (CLP). A total of 3,860 CL/P cases (70.8%) occurred as isolated anomalies and 1,589 (29.2%) were associated with other defects such as multiple congenital anomalies of unknown origin (970), chromosomal (455) and recognized syndromes (164). Associated malformations were more frequent in infants who had CLP (34.0%) than in infants with CL only (20.8%). Among multi-malformed infants, 2 unrelated anomalies were found in 351 cases, 3 in 242 cases, and 4 or more in 377 cases. Among 5,449 CL/P cases, 4,719 were live births (LB) (86.6%), 203 stillbirths (SB) (3.7%), while 508 (9.3%) were terminations of pregnancy (ToP). CL/P occurred significantly more frequently in males (M/F = 1.70), especially among total isolated cases (M/F = 1.87) and CLP isolated cases (M/F = 1.92). The study confirmed that musculoskeletal, cardiovascular, and central nervous system defects are frequently associated with CL/P. An association with reduction anomalies of the brain was found. This association suggests that clinicians should seek to identify structural brain anomalies in these patients with CL/P as the potential functional consequences may be important for rehabilitation and clinical management.     

On monitoring the multiply malformed infant. I: Case-finding, case-recording, and data handling in a Latin American program

The methods used by the Latin American Collaborative Study of Congenital Malformations (ECLAMC) for monitoring the birth prevalence of multiply malformed infants are based on a clinical-epidemiological approach oriented to the early detection of teratogenic agents. They consist of three steps: 1) the analysis of observed vs expected rates of all congenital anomalies (CA), including their isolated and associated forms; 2) the same type of analysis applied to each multiple congenital anomaly (MCA) pattern; and 3) a clinical case presentation reserved only for those considered as true MCA because of presence of three or more independent CA. During the period 1982-1983 299,231 infants were examined. Multiply malformed infants, excluding Down syndrome cases, were born at a rate of 4/10,000, 40% having syndromes (two or more interrelated CA), 30% anomaly pairs, ie, two independent CA, and 30% true MCA cases. In a program with 150,000 births per year, as in ECLAMC, this means about five true MCA cases per week, a number easily handled individually on a clinical basis.     

Characteristics and associated anomalies in radial ray deficiencies in Finland—A population‐based study

Upper‐limb defects with deficiencies of the radial ray have varying etiologies, with a low proportion of true Mendelian disorders. We carried out a population‐based study to elucidate the birth prevalence and clinical spectrum of radial ray deficiencies in Finland. We identified all births with radial ray deficiency reported to the Finnish Register of Congenital Malformations in 1993–2005. Altogether 138 cases were identified (123 live births), with a birth prevalence of 1.83 per 10,000 births and a live birth prevalence of 1.64 per 10,000 live births. The proportion of infant deaths was as high as 35%. The majority of the cases were associated with known syndromes or multiple anomalies; only 13% were true isolated radial ray deficiencies. The most common syndrome was trisomy 18, and the most common in multiple anomalies was VACTERL association. In 8.7% of cases an association between radial ray deficiency and heart anomaly was observed. The high proportion of cases with associated major anomalies indicates that radial ray deficiency can be regarded isolated only after thorough assessment of the various organ systems in an affected infant. © 2013 Wiley Periodicals, Inc.     

Classification and birth prevalence of orofacial clefts

To determine the proportion and birth prevalence of “typical” orofacial clefts (cleft lip (CL), cleft palate (CP), cleft lip and palate (CLP)) and “atypical” clefts (median, transversal, or oblique facial clefts) and the conditions in which they occur, we analyzed a population-based sample of 4,433 cases ascertained from 2,509,881 California births. We classified cases into: isolated cleft anomalies, sequences of the primary defect, chromosomal aberrations, monogenic syndromes, results of known teratogens, associations, multiple congenital anomaly (MCA) of unknown etiology, or conjoined twins. The birth prevalence of isolated CL±P was 0.77 per 1,000 births (CL 0.29/1,000, CLP 0.48/1,000) and of isolated CP, 0.31 per 1,000 births. Non-Hispanic Whites had the greatest prevalence of isolated clefts, Asians slightly lower prevalences, and Blacks the lowest. Asians had the lowest prevalence of Robin sequence and non-Hispanic Whites the highest, twice that of Hispanics. Hispanics, followed by Asians, had the highest prevalence of CL±P with MCA; non-Hispanic Whites had the lowest. Asians had the lowest prevalence of CP; in Whites and Hispanics it was almost twice as high. Blacks had the highest CL:CLP ratio, followed by non-Hispanic Whites and Asians; Hispanics had the lowest. Isolated anomalies constituted 61.67% of clefts. In the total sample there were 3.9% sequences, 8.79% chromosomal aberrations, 6.02% monogenic syndromes, 0.2% known teratogens, 0.79% associations, 18.55% MCA of unknown etiology, and 0.1% in conjoined twins. This study supports evaluation of each child on a “case” level, and provides a framework for genetic counseling and other studies focused on causes and prevention of these serious anomalies. Am. J. Med. Genet. 75:126–137, 1998. © 1998 Wiley-Liss, Inc.     

Anorectal anomalies associated with or as part of other anomalies

Anorectal anomalies occurring with other anomalies or as part of syndromes were analyzed to determine how their epidemiological characteristics differed from those of isolated anal anomalies. Almost 15% of cases were chromosomal, monogenic or teratogenic syndromes, whereas the rest were of unknown cause including sequences (9.3%), VACTERL associations (15.4%) and multiple congenital anomalies (MCA) (60.2%). Almost half of babies with MCA had one or two VACTERL anomalies with distribution frequencies that did not differ significantly from those in babies with the full VACTERL association. There were considerable differences in the frequency of the VACTERL association among babies with different types of anorectal anomaly. Babies with anal anomalies occurring with sequences, VACTERL or MCA showed the same sex differences as babies with isolated anal anomalies, namely male predominance in anal atresia without fistula or cloaca, no sex difference in anal atresia with fistula, and female predominance in ectopic anus and congenital anal fistula. These anomalies, however, were associated with significantly lower mean gestational lengths and birth weights, and higher frequencies of fetal death and pregnancy termination than babies with isolated anal anomalies. Twins were more frequent in sequences, VACTERL and MCA than in isolated anomalies, monogenic syndromes or chromosome anomalies. Five cases were conjoined twins, representing 15% of all cases of twin pregnancies with an anal anomaly. Indeterminate sex was more frequent in babies with anal atresias without fistula than in those with fistula. Anal anomalies are defects of blastogenesis attributable to disorders in expression of pattern determining genes. The differential sex involvement in different types of anal anomaly may be manifestations of expression of the HY/SRY genes during blastogenesis or of X-linkage.     

Secular trends in congenital anomaly‐related fetal and infant mortality in Canada, 1985–1996

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age‐specific and category‐specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985–1996. Comparisons of the rates between 1985–1987 and 1994–1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985–1987 to 78.6 per 100,000 total births in 1994–1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20–21 weeks of gestation increased approximately five‐fold (relative risk [RR] = 4.83, 95% CI = 3.28–7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37–41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50–0.97). Fetal death rates among pregnancies at 20–25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly‐related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years. © 2001 Wiley‐Liss, Inc.     

Congenital defects of the limbs in stillbirths: Data from a population-based study

We analyzed limb deficiencies occurring in stillbirths with congenital anomalies registered in the Health Surveillance Registry of British Columbia between the years 1964 and 1984. Thirty stillborn infants presenting with various defects of the limbs were found during this time, giving an incidence of 39.52 in 10,000 stillbirth (1:253). This incidence is significantly higher than the incidence among liveborn individuals in the Province (5.97 in 10,000 livebirths or 1:1,842). Most cases involved the upper limbs, and most frequently the radius. Additional anomalies were present in 77% of cases, compared to 48% in liveborns. The study of stillbirth with congenital anomalies provides important information regarding the spectrum of birth defects seen in this group. This may be of relevance because of improved survival possibilities due to advances in perinatal care. © 1993 Wiley-Liss., Inc. © 1993 Wiley-Liss, Inc.     

Clinical/epidemiological analysis of malformations

To investigate the heterogeneity of congenital malformations, we analyzed the distribution of 14 selected anomalies among 11,421 children with isolated defects and with different patterns of multiple congenital anomalies (MCA). Our study showed a marked variability in the distribution of each of these malformations. For example, although anophthalmia/microphthalmia, cleft palate, and limb deficiency were observed in all etiological categories of syndromes, no case with anencephaly was identified among the 1,244 children with different syndromes. Diaphragmatic hernia, esophageal atresia +/- tracheoesophageal fistula, and gastroschisis were not found in any monogenic syndrome in this sample. These observations may be of help to the clinician in the evaluation of individual children with MCA.     

Trisomy 13 and 18—Prevalence and mortality—A multi‐registry population based analysis

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty‐four population‐ and hospital‐based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data‐reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3–2.06), and for T18 was 4.08 (95% CI 3.01–5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38–0.72), and for T18 was 1.07 (95% CI 0.77–1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1‐year follow‐up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.     

Epidemiological analysis of rare polydactylies

This work includes all cases with extra digits (polydactyly) registered from a birth sample of over four million births aggregated from two comparable birth series: the Latin-American Collaborative Study of Congenital Malformations: ECLAMC (3,128,957 live and still births from the 1967 to 1993 period), and the Spanish Collaborative Study of Congenital Malformations: ECEMC (1,093,865 livebirths from April 1976 to September 1993, and 7,271 stillbirths from January 1980 to September 1993). All but 2 of 6,912 registered polydactyly cases fit well into one of the following 11 pre-established polydactyly types (observed number of cases in parentheses): Postaxial hexadactyly (5,345), Preaxial-I hexadactyly (1,018), Seven or more digits (57), synpolydactyly (15), crossed polydactyly (45), 1st digit triphalangism (33), 2nd digit duplication (39), 3rd digit duplication (18), 4th digit duplication (22), Haas polysyndactyly (3), and high degree of duplication (4). The birth prevalence rates observed in both series were similar except for postaxial polydactyly, which was more frequent in the ECLAMC (150.2/100,000) than in the ECEMC (67.4/100,000), as expected due to the higher African Black ethnic extraction of the South-American than of the Spanish populations. This similar frequency for the rare polydactylies (5.4 per 100,000 in South America and 5.7 in Spain), and for each one of the 9 categories, suggests that the values reported here are valid for most populations. The rare polydactylies are frequently syndromal: one third of them (77/236) were found in association with other congenital anomalies, 11.0% (26/236) in MCA cases and 21.6% (51/236) in recognized syndromes. © 1996 Wiley-Liss, Inc.     

A review of supernumerary and absent limbs and digits of the upper limb

For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12–23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.     

Associated nonurinary congenital anomalies among infants with congenital anomalies of kidney and urinary tract (CAKUT)

Infants with congenital anomalies of kidney and urinary tract (CAKUT) often have other associated anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in CAKUT in a defined population from northeastern France. The associated anomalies in CAKUT were collected in all livebirths, stillbirths and terminations of pregnancy during 26 years in 346,831 consecutive births of known outcome in the area covered by our population based registry of congenital anomalies. Of the 1678 infants with CAKUT born during this period (prevalence at birth of 48.4 per 10,000), 563 (34%) had associated anomalies. There were 119 (7%) patients with chromosomal abnormalities including 33 trisomies 18 (2%), and 168 (10%) nonchromosomal recognized dysmorphic conditions. There were no predominant recognized dysmorphic conditions, but VA(C)TER(L) association (3%). However, other recognised dysmorphic conditions were registered including Meckel–Gruber syndrome (2%), and prune belly syndrome (1%). Two hundred seventy six (16%) of the patients had multiple congenital anomalies, non syndromic, non chromosomal (MCA). Anomalies in the musculoskeletal, the digestive, the cardiovascular and the central nervous systems were the most common other anomalies. Prenatal diagnosis was obtained in 71% of dysmorphic syndromes with CAKUT. In conclusion the overall prevalence of associated anomalies, which was one in three infants, emphasizes the need for a thorough investigation of infants with CAKUT. The most commonly associated major nonurinary anomalies involved the musculoskeletal system, followed by the digestive, the cardiovascular and the central nervous systems. A routine screening for other anomalies may be considered in infants and in fetuses with CAKUT. One should be aware that the anomalies associated with CAKUT can be classified into a recognizable anomaly syndrome or pattern in one out of six infants with CAKUT.