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 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.     

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.     

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.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Associated malformations and chromosomal anomalies in 42 cases of prenatally diagnosed diaphragmatic hernia

We present a retrospective study of the frequency and type of associated malformations and chromosomal anomalies in 42 consecutive cases of congenital diaphragmatic hernia (CDH) diagnosed in utero during the period from 1985 to 1999. In 26% (11/42) of the cases, associated malformations were detected. Chromosomal anomalies were present in 9.5% (4/42). In this group of 15 cases (15/42 = 36%) with associated malformations or chromosomal anomalies, all cases, except one, had prenatal sonographic evidence of additional problems. The survival rate of fetuses with CDH and associated malformations or chromosomal anomalies was poor (1/15). Therefore, the overall survival rate of in utero‐diagnosed CDH was only 31% (13/42), while isolated left CDH had a survival rate of 52% (12/23). The in utero diagnosis of CDH implies a detailed echographic examination to exclude additional anomalies. The risk for a syndromal or chromosomal malformation becomes small when no additional anomalies are seen on ultrasound.     

Associated malformations in patients with anorectal anomalies

Patients with congenital anorectal malformations (ARM) often have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalences at birth of associated malformations in patients of a geographically defined population with ARM which were collected between 1979 and 2003 in 334, 262 consecutive births. Of the 174 patients with ARM during the study period, 49.4% had associated malformations. Patients with associated malformations were further classified into groups with nonsyndromic multiple congenital anomalies; chromosomal abnormalities; nonchromosomal syndromes including Townes-Brocks, Walker-Warburg, Ivemark, Fetal alcohol, Klippel-Feil, Pallister-Hall, Facio-auriculo-vertebral spectrum, deletion 22q11.2; sequences, including OEIS, Pierre Robin and sirenomelia; and associations including VATER and MURCS. Malformations of the urogenital system (81.1%) and of the skeletal system (45.5%) were the most common other congenital anomalies occurring with ARM in multiply malformed patients without recognized entities, followed by malformations of the cardiovascular system, the digestive system, and the central nervous system. Weight, length, and head circumference of children with ARM and multiple associated malformations were lower than in controls, as was the weight of the placenta. Prenatal detection by fetal ultrasonographic examination was rarely made in isolated ARM. However, even in multiple associated malformations, prenatal detection by fetal ultrasonographic examination had a low sensitivity, 36%. In conclusion the overall prevalence of malformations, which was close to 1 in two infants, emphasizes the need for a thorough investigation of patients with ARM. A routine screening for other malformations may be considered in patients with ARM, and genetic counseling seems warranted in most of these complicated cases.     

Trend of congenital anomalies over 20 years ascertained by population-based monitoring in Ishikawa Prefecture, Japan

ABSTRACT  Monitoring in Ishikawa Prefecture (mean population; 1,150,000), during the 20-year period from 1981 to 2000, involved monitoring the prevalence of congenital anomalies starting at gestational week 22. The main objectives of the present study were (1) to investigate the trend over the past 20 years in the prevalence of congenital anomalies, and (2) to investigate whether there is area accumulation in congenital anomalies or not In addition, the prevalence of well-known risk factors such as smoking, drinking and family history among cases with congenital anomalies was analyzed to obtain clues to the background of such anomalies. During the 20 years, more than 200,000 births have been observed. Thirty-three selected congenital anomalies, consisting mainly of external anomalies, were analyzed in this study. The percentage of children born with congenital anomalies did not change markedly between the first and second halves of the monitoring period, remaining at approximately 4.5/ 1,000 births. There was also no significant change in annual trends in either Ishikawa Prefecture as a whole or in the three regions within Ishikawa. The prevalence of congenital anomalies by type showed a significant decrease in anencephaly and spina bifida. In contrast, Down syndrome and microcephaly increased significantly. The mean maternal age for Down syndrome increased significantly from the first-half period to the second-half period. The percentage of children with polydactyly whose mother smoked were relatively higher than that for the other congenital anomalies.     

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 malformations in patients with limb reduction deficiencies

Infants with limb reduction deficiencies (LRD) often have other associated congenital malformations. The purpose of this investigation was to assess the prevalence and the types of associated malformations in a defined population. This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for malformations was continued until 1 year of age. The associated malformations in infants with LRD were collected in all livebirths, stillbirths and terminations of pregnancy during 25 years in 347,810 consecutive births in the area covered by our population based registry of congenital malformations. Of the 271 LRD infants born during this period, representing a prevalence of 7.8 per 10,000, 57.9% had associated malformations. There were 17(6.3%) patients with chromosomal abnormalities including 10 trisomies 18, and 62 (22.9%) nonchromosomal recognized dysmorphic conditions. There were no predominant recognized dysmorphic conditions, but VA(C)TER(L) association. However numerous recognized dysmorphic conditions were registered including Poland, ectrodactyly-ectodermal dysplasia-clefting, oral-facial-digital, Klippel–Trenaunay–Weber, oculo-auriculo-vertebral defect spectrum, CHARGE, Townes-Brocks, Moebius, Du Pan, Smith-Lemli-Opitz, hypoglossia-hypodactyly, amniotic band, De Lange, Rubinstein-Taybi, Fanconi, radius aplasia- thrombocytopenia, Roberts, Holt-Oram, and fetal diethylstilbestrol. Seventy eight (28.8%) of the patients were multiply, non-syndromic, non chromosomal malformed infants (MCA). Malformations in the cardiac system, in the genital system, and in the central nervous system were the most common other malformations, 11.4%, 9.4%, and 7.7% of the associated malformations, respectively, followed by malformations in the renal system (4.8%), and in the digestive system (4.6%). Prenatal diagnosis was performed in 48.4% of dysmorphic syndromes with LRD. The overall prevalence of associated malformations, which was more than one in two infants, emphasizes the need for a thorough investigation of infants with LRD.A routine screening for other malformations especially cardiovascular system, urogenital system, central nervous system, and digestive system may be considered in infants and in fetuses with LRD.     

Prevalence,prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990–2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100 000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.     

Congenital limb deficiencies and major associated anomalies in Alberta for the years 1980–2012

There is a wide range of the proportion of congenital anomalies associated with limb deficiencies reported in the literature. This variation is primarily attributed to methodology and classification differences. The distribution of associated anomalies among cases with congenital limb deficiencies in Alberta born between January 1, 1980 and December 31, 2012 is described. Of the 170 cases identified, most were live born (75.3%), male (61.8%), had longitudinal limb deficiencies (78.8%), and had associated anomalies outside the musculoskeletal system (77.6%). Significant associations between the preaxial longitudinal group and the central nervous, gastrointestinal, and cardiovascular systems are reported as well as between the postaxial longitudinal group and congenital hip and foot anomalies. Probable and possible syndrome diagnoses are described for cases with recognized malformation patterns.     

Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays

Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytogenetic tests currently used for the detection of such chromosomal rearrangements are low resolution and limited coverage of the genome. Thus, it is likely that children with MCA may have submicroscopic chromosomal rearrangements that are not detectable by current techniques. We report the use of a commercially available, oligonucleotide-based microarray for genome-wide analysis of copy number alterations. First, we validated the microarray in patients with known chromosomal rearrangements. Next, we identified previously undetected, de novo chromosomal deletions in patients with MCA who have had a normal high-resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH) analysis. These findings indicate that high-density, oligonucleotide-based microarrays can be successfully used as tools for the detection of chromosomal rearrangement in clinical samples. Their higher resolution and commercial availability make this type of microarray highly desirable for application in the diagnosis of patients with multiple congenital defects.     

High‐resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting

Wincent J, Anderlid B‐M, Lagerberg M, Nordenskjöld M, Schoumans J. High‐resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting. Microarray‐based comparative genomic hybridization (array‐CGH) enables genomewide investigation of copy‐number changes at high resolution and has recently been implemented as a clinical diagnostic tool. In this study we evaluate the usefulness of high‐resolution arrays as a diagnostic tool in our laboratory and investigate the diagnostic yield in the first 160 patients who were clinically referred for investigation of developmental delay (DD)/multiple congenital anomalies (MCA). During this period both 38K BAC‐arrays and 244K oligonucleotide‐arrays were used. Copy‐number variations (CNVs) not previously reported as normal variants were detected in 22.5% of cases. In 13.1% the aberrations were considered causal to the phenotype and in 9.4% the clinical significance was uncertain. There was no difference in diagnostic yield between patients with mild, moderate or severe DD. Although the effective resolution of the 244K oligonucleotide‐arrays was higher than the 38K BAC‐array, the diagnostic yield of both platforms was approximately equal and no causal aberrations <300 kb were detected in this patient cohort. We experienced that increasing the resolution of a whole genome screen in the diagnostic setting has its drawback of detecting an increased number of CNVs with uncertain contribution to a phenotype. Based on our experiences, array‐CGH is recommended as the first‐step analysis in the genetic evaluation of patients with DD and/or MCA.     

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.     

Retrospective analysis of fetal vertebral defects: Associated anomalies,etiologies, and outcome

Our objectives were to describe fetal cases of vertebral defects (VD), assess the diagnostic yield of fetal chromosomal analysis for VD and determine which investigations should be performed when evaluating fetal VD. We performed a retrospective chart review for fetuses with VD seen between 2006 and 2015. Cases were identified from CHU Sainte‐Justine's prenatal clinic visits, postmortem fetal skeletal surveys, and medical records. Cases with neural tube defects were excluded. Sixty‐six fetuses with VD were identified at a mean gestational age of 20 weeks. Forty‐seven (71.2%) had associated antenatal anomalies, most commonly genitourinary, skeletal/limb, and cardiac anomalies. Thirteen mothers (19.7%) had pregestational diabetes (95% CI [10.1%–29.3%]). Fifty‐three cases had chromosomal analysis. Three had abnormal results (5.6%): trisomy 13, trisomy 22, and 9q33.1q34.11 deletion. Thirty‐four (51.5%) pregnancies were terminated, one led to intrauterine fetal demise and 31 (46.9%) continued to term. Of 27 children who survived the neonatal period, 21 had congenital scoliosis and 3 had spondylocostal dysostosis. Seven had developmental delay. In conclusion, prenatal evaluation of fetuses with VD should include detailed morphological assessment (including fetal echocardiogram), maternal diabetes screening, and chromosomal microarray if non‐isolated. Our findings provide guidance about management and counseling after a diagnosis of fetal VD.     

Congenital anomalies concomitant with persistent primary congenital hypothyroidism

The Israeli national neonatal screening program for congenital hypothyroidism (CH) was initiated in May 1978. The overall incidence of persistent primary congenital hypothyroidism (PPCH) during the first 10 years of screening was 1:2,950 live births. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with PPCH and to compare it with the Israeli Birth Defect Monitoring System data. Among 243 PPCH infants on whom adequate data were available, 38 infants (15.6%) had associated congenital anomalies. Fourteen infants had congenital cardiac anomalies (5.8%): VSD (n = 7), PDA (n = 3), PS (n = 2), one mitral insufficiency, and one congenital atrial flutter. Eight children (3.3%) had congenital dislocation of the hip; their M:F ratio was 3:5 similar to the M:F ratio in CH (unlike the ratio in the general population). Some additional anomalies were considerably more common than in the general population. It is reasonable to assume that teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETA. © 1992 Wiley-Liss, Inc.     

Associated malformations among infants with neural tube defects

Infants with neural tube defects (NTDs) often have associated congenital anomalies. The reported frequency and types of associated malformations vary between different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with NTDs in a geographically well-defined population from 1979 to 2008 of 402,532 consecutive births. Of the 441 infants with NTDs born during this period, 20.4% had associated malformations. Infants with associated malformations were divided into those with recognizable conditions [11 (2.5%) infants with chromosomal and 23 (5.2%) with non-chromosomal conditions], and those without recognizable conditions [56 (12.7%) infants with multiple malformations]. Associated malformations were more frequent among infants with encephalocele (36.8%) than those with anencephaly (11.5%) or spina bifida (23.8%). Oral clefts and malformations in the musculoskeletal, renal and cardiovascular systems were the most commonly observed associated anomalies. The frequency of associated malformations in infants with NTDs emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations, especially facial clefts and musculoskeletal, renal and cardiac anomalies, may need to be considered in infants with NTDs, and referral of these infants for genetics evaluation and counseling seems warranted.     

Associated malformations in patients with esophageal atresia

Esophageal atresia is a common type of congenital malformation. The etiology of esophageal atresia is unclear and its pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with esophageal atresia, we conducted this study in a geographically well-defined population, evaluating the birth prevalence of esophageal atresia and associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 99 patients with esophageal atresia, 46 (46.5%) had associated malformations. These included patients with chromosomal abnormalities (8 patients, 8%); non-chromosomal recognized syndromes (4 patients), including one each CHARGE syndrome, Fanconi anemia, Fryns syndrome, and Opitz G/BBB syndrome; associations including VACTERL (10 patients), and one schisis; one oculo-auriculo-vertebral spectrum; one malformation complex, a sirenomelia, and non-syndromic multiple congenital anomalies (MCA) (21 patients, 21%). Malformations of the cardiovascular system (24%), urogenital system (21%), digestive system (21%), musculoskeletal system (14%), and central nervous system (7%) were the most common other congenital malformations occurring in patients with esophageal atresia and non-syndromic MCA. We observed a high prevalence of total malformations and specific patterns of malformations associated with esophageal atresia which emphasizes the need to evaluate all patients with esophageal atresia for possible associated malformations. The malformations associated with esophageal atresia could be classified into a recognizable malformation syndrome or pattern in 25 out of 46 patients (54%).