Omphalocele and gastroschisis and associated malformations

The etiology of gastroschisis and omphalocele is unclear and their pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with omphalocele and gastroschisis, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 86 patients with omphalocele, 64 (74.4%) had associated malformations. These included patients with chromosomal abnormalities (25, 29.0%); non-chromosomal syndromes including Beckwith-Wiedemann syndrome, Goltz syndrome, Marshall-Smith syndrome, Meckel-Gruber syndrome, Oto-palato-digital type II syndrome, CHARGE syndrome, and fetal valproate syndrome; malformation sequences, including ectopia cordis, body stalk anomaly, exstrophy of bladder, exstrophy of cloaca, and OEIS (Omphalocele, Exstrophy of bladder, Imperforate anus, Spinal defect); malformation complexes including Pentalogy of Cantrell, and non-syndromic multiple congenital anomalies (MCA) (26, 30.2%). Malformations of the musculoskeletal system (31, 23.5%), urogenital system (27, 20.4%), cardiovascular system (20, 15.1%), and central nervous system (12, 9.1%) were the most common other congenital malformations in patients with omphalocele and non-syndromic MCA. Of the 60 patients with gastroschisis, 10 (16.6%) had associated malformations. In contrast to omphalocele, gastroschisis was rarely associated with a complex pattern of malformation, that is, one each (1.7%) with a chromosomal abnormality (trisomy 21), sequence (amyoplasia congenita), unspecified dwarfism, and 7 (11.7%) with MCA. We observed a striking difference in the prevalence of total malformations (74.4% vs. 16.6%, P < 0.001) and specific patterns of malformations associated with omphalocele and gastroschisis which emphasizes the need to evaluate all patients with omphalocele and gastroschisis for possible associated malformations. Malformation surveillance programs should be aware that the malformations associated with omphalocele can be often classified into a recognizable malformation syndrome or pattern (44.2%).     

Patterns of malformation associated with esophageal atresia/tracheoesophageal fistula: A retrospective single center study

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is one of the most common gastrointestinal birth defects. It can occur in isolation or in association with other birth defects or genetic syndromes. We retrospectively reviewed the EA/TEF cases evaluated at Rady Children's Hospital San Diego (San Diego, CA) between 2007 and 2016. Data were collected for 157 patients. The majority of patients (105, 66.8%) had an associated major malformation present, and 52 patients (33.1%) had isolated EA/TEF. The patients with associated malformations were distributed as follows: 16 patients (10.2%) had a known genetic syndrome (the most common being Trisomy 21 in 11 patients); six patients (3.8%) had a suspected genetic syndrome; one patient had a suspected teratogenic syndrome (diabetic embryopathy); 30 patients had VACTERL association (19.1%); 32 patients had a “partial VACTERL” association (only two VACTERL‐type defects without other malformation); nine patients (5.7%) had one additional non‐VACTERL‐type birth defect, two patients had VACTERL‐type defects plus auricular malformations; and nine patients (5.7%) were classified as “unknown syndrome.” A classification of the patterns of malformation of patients with congenital EA/TEF is proposed based on reviewing the data of this relatively large and phenotypically diverse patient group.     

Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association: review of genetics and epidemiology

Oesophageal atresia and/or tracheo-oesophageal fistula are relatively common malformations occurring in approximately 1 in 3500 births. In around half of the cases (syndromic oesophageal atresia), there are associated anomalies, with cardiac malformations being the most common. In the remainder (non-syndromic cases), oesophageal atresia/tracheo-oesophageal fistula occur in isolation. Data from twin and family studies suggest that genetic factors do not play a major role, and yet there are well-defined instances of this malformation where genetic factors clearly are important. This is highlighted by the recent identification of no fewer than three separate genes with a role in the aetiology of oesophageal atresia: those for Feingold syndrome (N-MYC), anophthalmia-oesophageal-genital (AEG) syndrome (SOX2), and CHARGE syndrome (CHD7). Additional support for genetic factors in this malformation comes from chromosomal studies and mouse models. This paper reviews current knowledge of the genetics and epidemiology of the different oesophageal atresia/tracheo-oesophageal fistula syndromes and associations.     

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.     

Familial recurrence of tracheoesophageal fistula and associated malformations

Tracheoesophageal fistula (TEF) may occur as an isolated malformation or together with other malformations. To determine the recurrence risk of TEF or associated malformations in children and sibs, and to determine the frequency of associated malformations in index patients, we reviewed the Mayo Clinic records of 204 patients with TEF. Also, questionnaires were sent to patients or relatives. Questions were designed to determine whether the patient and relatives had TEF and/or related organ system (including VACTERL) malformations. The VACTERL association is a disorder characterized by 3 or more of the following: vertebral, anal, cardiac, renal, or radial anomalies, and TEF. One hundred twenty-eight families returned a completed questionnaire, and 140 index patients were ascertained based on complete medical records, questionnaire, and/or autopsy. Forty-one (29.3%) of 140 index patients had TEF with one other VACTERL malformation, and twenty-four (17.1%) of 140 index patients had TEF with at least two other VACTERL malformations. Of the 347 sibs of index patients, 5 (1.4%) had one VACTERL malformation each, including 1 sib with esophageal atresia (EA) without TEF. Of the 41 children of index patients, 1 (2.4%) had TEF plus two other VACTERL malformations; another had one non-TEF VACTERL malformation. From our study, the largest reported population of TEF patients to date, we conclude that: 1) nearly half (46%) of patients with tracheoesophageal fistula will exhibit other VACTERL malformations; 2) the recurrence risk for individuals with TEF to have affected children is 2–3%; and 3) there is an increased risk to relatives of TEF patients to exhibit other VACTERL malformations. © 1996 Wiley-Liss, Inc.     

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.     

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.     

Gastrointestinal disorders in Down syndrome

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10‐year follow‐up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow‐up as well as adequate development and greater quality of life for patients with Down syndrome and their families.     

Genetic factors in esophageal atresia,tracheo-esophageal fistula and the VACTERL association: Roles for FOXF1 and the 16q24.1 FOX transcription factor gene cluster,and review of the literature

Esophageal atresia with/without tracheo-esophageal fistula is a relatively common malformation, occurring in around 1 in 3500 births. In around half of cases, additional malformations are present, forming either a syndrome of known genetic aetiology, or a recognised association, of which the VACTERL association (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal and Limb malformations) is the most recognised. Recently, microdeletions of the FOX gene cluster at 16q24.1, comprising four genes, FOXF1, MTHFSD, FOXC2 and FOXL1, were reported to cause a phenotype resembling VACTERL association, with vertebral anomalies, gastro-intestinal atresias (esophageal, duodenal and anal), congenital heart malformations, and urinary tract malformations, as well as a rare lethal developmental anomaly of the lung, alveolar capillary dysplasia. This article reviews these new data alongside other genetic causes of syndromic esophageal atresia, and also highlights information from relevant mouse models, particularly those for genes in the Sonic Hedgehog pathway.     

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.     

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.     

Congenital gastrointestinal system malformations in a 5-year post mortem series

The aim of this study was to determine the types and frequencies of congenital gastroinstestinal (G-I) tract malformations on post mortem in the period from 1996 to 2000. Autopsy protocols of aborted fetuses, stillborn infants and infants that died within 7 days after delivery were retrieved from the archive and studied. Cases of cleft lip and/or palate, biliary tract, pancreatic and diaphragmal malformations were not included in the study. During the mentioned period, 1251 autopsy was performed with 127 showing some malformation. G-I tract malformation was diagnosed in 37 cases (2.9% and 29.1%, respectively). Most frequent malformations were atresias at the different level of the G-I tract (56.75%), followed by omphalocoele (35.13%) and gastroschisis (8.1%). Of atresias, the most frequent were oesophageal and anorectal (38.1% of atresias, each). A striking male preponderance (2.36:1) in the frequency of G-I malformations was noticed. Isolated G-I malformations were found in 32.4%, different but simultaneous G-I malformations in 5.4% and association with other organ system(s) malformations in 62.2%. Omphalocoele and anorectal atresia were associated with other organ system malformation(s) in 34.8%, each. Other organ systems affected by malformation besides the G-I tract were cardiovascular system (65.21%), urogenital system (also 65.2%), gastrointestinal system with the malformation of another kind or atresia at the different level (17.4%), CNS (17.4%), skeletal system (26.1%) and other organs or systems (30.7%).     

Major congenital malformations in Down syndrome

We studied major malformations in 5,581 infants with Down syndrome (DS) from three registers of congenital malformations. The prevalence at birth of 23 different malformations was compared with the program-specific rates for each malformation in non-DS infants. An about 300 times risk increase was seen for annular pancreas, cataracts and duodenal atresia and an about 100 times risk increase for megacolon and choanal atresia. Esophageal, anal and small bowel atresia, preaxial polydactyly, and omphalocele all showed risk increases between 10 and 30 times. Statistically significantly elevated risk ratios around 3–5 were seen for cleft palate, cleft lip/palate, and limb deficiencies. No increased risk was seen for neural tube defects, hydrocephaly, microtia, renal agenesis or severe dysgenesis, hypospadias or polydactyly other than preaxial. Oral clefts were more often present in DS in the Swedish material than in the other two materials. Cardiac defects were registered in 26% of all cases (varying between programs) but 28% of the cardiac defects were unspecified. DS infants born to women younger than 25 years had a significantly increased risk for megacolon and there was a trend of increasing risk for esophageal or anal atresia with maternal age. A decreased risk for cardiac defect in DS infants born to teenage mothers was found, quite pronounced for endocardial cushion defects and ventricular septum defects. There were no statistically significant differences in the sex distribution of specific malformations in infants with DS and in non-DS infants. © 1996 Wiley-Liss, Inc.     

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.     

Microdeletion 22q11 and oesophageal atresia

Oesophageal atresia (OA) is a congenital defect associated with additional malformations in 30-70% of the cases. In particular, OA is a component of the VACTERL association. Since some major features of the VACTERL association, including conotruncal heart defect, radial aplasia, and anal atresia, have been found in patients with microdeletion 22q11.2 (del(22q11.2)), we have screened for del(22q11.2) by fluorescent in situ hybridisation (FISH) in 15 syndromic patients with OA. Del(22q11.2) was detected in one of them, presenting with OA, tetralogy of Fallot, anal atresia, neonatal hypocalcaemia, and subtle facial anomalies resembling those of velocardiofacial syndrome. The occurrence of del(22q11.2) in our series of patients with OA is low (1/15), but this chromosomal anomaly should be included among causative factors of malformation complexes with OA. In addition, clinical variability of del(22q11.2) syndrome is further corroborated with inclusion of OA in the list of the findings associated with the deletion.     

Terminal 4q deletion and 8q duplication in a patient with CHARGE-like features

The CHARGE syndrome is a multiple congenital malformation syndrome that usually results from deletion or heterozygous loss of function mutations of the chromodomain helicase DNA-binding protein 7 (CHD7) gene at 8q12.1. Besides CHD7-related cases, some patients with CHARGE-like phenotype have been reported with chromosomal imbalances. We describe a patient with a pattern of malformations reminiscent of CHARGE syndrome: choanal atresia, facial dysmorphism (micrognathia, hypertelorism, epicanthic folds, and depressed, broad nasal bridge), cardiovascular malformations, cryptorchidism, and developmental delay. He had duplication 8q and deletion 4q derived from paternal translocation t(4;8)(q34;q22.1). CHD7 mutation or deletion was excluded. The present report to the best of our knowledge is the only one describing an unbalanced translocation t(4;8) and CHARGE-like phenotype.     

胎儿动脉导管缺如的尸体解剖分析

目的对胎儿先天性动脉导管缺如进行尸体解剖分析,以提高该疾病诊断的精准性。方法回顾2011年1月至2019年9月北京安贞医院经超声心动图畸形筛查发现胎儿先天性心脏畸形引产而进行尸体解剖病例400例,检查胎儿心血管畸形及内脏的畸形情况,对其动脉导管缺如进行分析总结。结果400例胎儿先天性心脏病中,动脉导管缺如24例,检出率6%,男女各12例,左位主动脉弓19例,右位主动脉弓5例,21例具有肺动脉主干,3例无肺动脉主干及分支。具体情况如下:(1)肺动脉狭窄伴动脉导管缺如15例,伴发主要心血管畸形:单心室6例,房间隔缺损6例,单心房4例,右心房异构4例,右心室双出口4例,静肺脉异位引流4例,法洛四联症3例,永存左上腔静脉3例;(2)肺动脉闭锁伴动脉导管缺如7例,3例无肺动脉主干,4例肺动脉闭锁伴有狭窄的肺动脉主干,均可见体-肺动脉侧支;(3)法洛四联症伴肺动脉瓣缺如综合征及动脉导管缺如1例,肺动脉扩张;(4)主-肺动脉间隔缺损伴动脉导管缺如1例,肺动脉正常。动脉导管缺如伴发主要心外畸形:脾缺如7例,肺异常7例,内脏反位7例。结论胎儿动脉导管缺如常合并复杂先天性心血管畸形;动脉导管缺如合并肺动脉闭锁常伴体-肺动脉侧支;内脏畸形与伴随的先天性心血管畸形有关。     

Congenital gastrointestinal defects in Down syndrome: a report from the Atlanta and National Down Syndrome Projects

We report Down syndrome (DS)-associated congenital gastrointestinal (GI) defects identified during a 15 year, population-based study of the etiology and phenotypic consequences of trisomy 21. Between 1989 and 2004, six sites collected DNA, clinical and epidemiological information on live-born infants with standard trisomy 21 and their parents. We used chi-squared test and logistic regression to explore relationships between congenital GI defects and infant sex, race, maternal age, origin of the extra chromosome 21, and presence of a congenital heart defect. Congenital GI defects were present in 6.7% of 1892 eligible infants in this large, ethnically diverse, population-based study of DS. Defects included esophageal atresia/tracheoesophageal fistula (0.4%), pyloric stenosis (0.3%), duodenal stenosis/atresia (3.9%), Hirschsprung disease (0.8%), and anal stenosis/atresia (1.0%). We found no statistically significant associations between these defects and the factors examined. Although not significant, esophageal atresia was observed more often in infants of younger mothers and Hispanics, Hirschsprung disease was more frequent in males and in infants of younger mothers and blacks, and anal stenosis/atresia was found more often among females and Asians.     

Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging

BACKGROUND: The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is a malformation of the female genitals (occurring in one in 4000 female live births) as a result of interrupted embryonic development of the Müllerian (paramesonephric) ducts. This retrospective study examined the issue of associated malformations, subtyping, and the frequency distribution of subtypes in MRKH syndrome. METHODS: Fifty-three MRKH patients were investigated using a newly developed standardized questionnaire. Together with the results of clinical and diagnostic examinations, the patients were classified into the three recognized subtypes [typical, atypical and MURCS (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia)]. RESULTS: The typical form was diagnosed in 25 patients (47%), the atypical form in 11 patients (21%), and the most marked form-the MURCS type-in 17 patients (32%). Associated malformations were notably frequent among the patients. Malformations of the renal system were the most frequent type of accompanying malformation, with 23 different malformations in 19 patients, followed by 18 different skeletal changes in 15 patients. CONCLUSIONS: In accordance with the literature, this study shows that associated malformations are present in more than a third of cases. Therefore, new basic guidelines for standard diagnostic classification involving patients with suspected MRKH are presented.     

CHARGE syndrome: Report of 47 cases and review

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells. Am. J. Med. Genet. 76:402–409, 1998. © 1998 Wiley-Liss, Inc.