Upper limb deficiencies and associated malformations: A population-based study

As part of an ongoing analysis of limb deficiencies occurring among 1,213,913 consecutive livebirths in British Columbia during the years 1952–1984, all cases with deficiencies of the upper limbs were analysed with a view to identifying associated patterns of anomalies. This analysis resulted in seven subgroups. For each subgroup, incidence figures for cases with and without additional anomalies were calculated separately. The proportion of cases with additional anomalies varied markedly by subgroup. For example, 89% of cases with longitudinal defects of the radius had additional malformations, while only 28% of cases with transverse defects of the radius had other organ anomalies (χ² = 40.55; P < 0.001, one degree of freedom). A preponderance of males was found among the cases with associated defects, particularly in the group with longitudinal defects of the radius (28 males, 14 females; χ² = 14.10; P < 0.001). Clustering of specific patterns of associated malformations is described within subgroups. © 1992 Wiley-Liss, Inc.     

Congenital defects of lower limbs and associated malformations: A population based study

As part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley-Liss, Inc.     

Upper limb deficiencies and associated malformations: a population-based study.

As part of an ongoing analysis of limb deficiencies occurring among 1,213,913 consecutive livebirths in British Columbia during the years 1952-1984, all cases with deficiencies of the upper limbs were analysed with a view to identifying associated patterns of anomalies. This analysis resulted in seven subgroups. For each subgroup, incidence figures for cases with and without additional anomalies were calculated separately. The proportion of cases with additional anomalies varied markedly by subgroup. For example, 89% of cases with longitudinal defects of the radius had additional malformations, while only 28% of cases with transverse defects of the radius had other organ anomalies (chi 2 = 40.55; P < 0.001, one degree of freedom). A preponderance of males was found among the cases with associated defects, particularly in the group with longitudinal defects of the radius (28 males, 14 females; chi 2 = 14.10; P < 0.001). Clustering of specific patterns of associated malformations is described within subgroups.     

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.     

Diaphragmatic defects and limb deficiencies - taking sides

Diaphragmatic defects and limb deficiencies usually occur as independent anomalies, as a polytopic field defect (in which ipsilateral anomalies might be expected) or as wider pattern of defects, potentially involving disturbance of laterality or the midline (in which bilateral or contralateral defects would occur). Data on cases from previous studies and/or the literature were used to determine whether there is an association between the sides involved in the defects. The 88 adequately described cases identified included 20 with de Lange syndrome, seven with Poland anomaly, four with trisomy 18, 52 with other patterns of multiple malformations and five with diaphragmatic and limb defects alone. Evaluation of the position of the limb (left, right, bilateral) and the diaphragmatic defects (left, right, bilateral) did not show significant association in patterns of sidedness (P = 0.48). In 56% of cases, the limb deficiencies were bilateral. Among the 32 unilateral cases, 19 (59%) were ipsilateral (15 left; 4 right) and 13(41%) were contralateral (P = 0.38). Eleven of the 13 contralateral cases had left sided diaphragmatic defects and right sided limb deficiency; four had de Lange syndrome and nine had other patterns of multiple anomalies. Only cases with Poland anomaly or otherwise isolated defects showed a trend towards ipsilateral defects. Most cases with multiple congenital anomalies, had limbs defects on both the right and left (57%) or both sides of the diaphragm were affected (an additional 10%), indicating a widespread dysmorphogenetic process rather than a more restricted field defect. In other cases, defects were bilateral or, if unilateral, reflected the propensities for diaphragmatic defects to more often involve the left side, and limb defects, the right.     

Renal defects and limb deficiencies in 197 infants: is it possible to define the "acrorenal syndrome"?

Dieker and Opitz in 1969 described the simultaneous occurrence of limb deficiencies (LDs) and renal anomalies (RAs) in three patients. Curran and Curran introduced in 1972 the term "acrorenal syndrome." Since then, the term "acrorenal syndrome" is used occasionally, but a well-circumscribed definition has never been established. On the other hand, the concept of an acrorenal polytopic developmental field defect was postulated by Opitz and others to explain the association between RAs and LDs. We undertook this study to investigate whether this acrorenal "syndrome" could be identified in a large group of cases with congenital RAs and a limb deficiency. Eleven birth defect registries that are part of the International Clearinghouse for Birth Defects Monitoring (i.e., registries of ICBDMS in Finland, France [Paris and Strasbourg], Israel, Italy [IPIMC and Emilia Romagna], Mexico, Northern Netherlands, South America, Spain, and the United States [Atlanta]) provided data on 815 infants who had a LD and at least one other major congenital anomaly. These 815 cases were ascertained among 5,163,958 births. We selected the 197 cases who had both a limb deficiency and a renal or urinary tract anomaly. In about 50% of these cases a diagnosis or a recognized phenotype was reported, with chromosomal aberrations and VACTERL being most frequent. In the group with no diagnosis or recognized phenotype (95 cases), we looked for (a) clustering of specific types of LDs and RAs, and (b) for clustering of associated anomalies, in order to find evidence for and be able to define better the term "acrorenal syndrome." Our data suggest that an association exists between LDs and RAs, possibly explained by the concept of the acrorenal polytopic developmental field defect. However, our dataset does not yield evidence for the existence of one distinct "syndrome," defined as a pattern of causally related multiple anomalies. Therefore, use of the term "acrorenal syndrome" should be avoided. Copyright 2004 Wiley-Liss, Inc.     

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.     

Systemic aplasia cutis congenita: A case report and review of the literature

Aplasia cutis congenita (ACC) belongs to a heterogeneous group of conditions characterized by a congenital absence of skin, usually on the vertex of the scalp. It can occur as an isolated defect or can be associated with a number of other congenital anomalies. Two cases of systemic ACC of a more severe and extensive type were recently reported. Here, we describe the third case of systemic ACC and review the available literature. A female infant was born with an extensive defect of the skin, a skull defect, imperforate hymen, and some other anomalies. She died soon after birth probably due to asphyxia and dehydration. We also compared the pathologic findings of the current case with those of the other two previously reported cases. This case suggests that systemic ACC might be recognized as a new syndrome. A limitation is that there is only 1 case, and it is difficult to gain a deeper understanding of its etiology and diagnostic criteria.     

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 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.     

Oculoauriculovertebral abnormalities in children of diabetic mothers

Maternal diabetes is known to have teratogenic effects. Malformations including neural tube defects, caudal dysgenesis, vertebral defects, congenital heart defects, femoral hypoplasia, and renal anomalies are described in infants of diabetic mothers. However, craniofacial anomalies have rarely been reported in such infants. Here we document craniofacial anomalies of patients born to diabetic mothers. We describe two patient populations: individuals evaluated through our genetics services for multiple malformations and individuals identified through a database search in our craniofacial clinic. The first group consists of 14 individuals evaluated in our genetics clinics who were born to diabetic mothers and had craniofacial anomalies. The second group consists of seven individuals who were identified from a craniofacial database search of patients with hemifacial microsomia and who were born to diabetic mothers. Thus, both groups were born to diabetic mothers and had hemifacial microsomia (67%), microtia (52%), hearing loss (43%), epibulbar dermoids (24%), and fused cervical vertebrae (24%). Therefore, the teratogenic effects of maternal diabetes probably include such craniofacial malformations as the oculoauriculovertebral/Goldenhar complex. Infants of diabetic mothers should be evaluated for craniofacial anomalies. Conversely, mothers of infants with craniofacial anomalies should be evaluated for diabetes to aid in counseling concerning cause and recurrence risks.     

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 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.     

Distal 8p deletion (8)(p23.1): An easily missed chromosomal abnormality that may be associated with congenital heart defect and mental retardation

We describe the clinical manifestations and molecular cytogenetic analyses of three patients with a similar distal deletion of chromosome 8. Each child had mild developmental delay and subtle minor anomalies. Two had cardiac anomalies but no other major congenital anomalies were present. High resolution G and R banding showed in all three patients del(8)(p23.1), but the breakpoint in case 1 was distal to 8p23.1, in case 2 was in the middle of 8p23.1, and in case 3 proximal to 8p23.1. Fluorescence in situ hybridization (FISH) studies with a chromosome 8 paint probe confirmed that no other rearrangement had occurred. FISH with a chromosome 8-specific telomere probe indicated that two patients had terminal deletions. Chromosome analysis of the parents of case 1 and mother of case 2 were normal; the remaining parents were not available for study. Thirteen individual patients including the three in this study, and three relatives in one family with del(8)(p23.1), have been reported in the past 5 years. Major congenital anomalies, especially congenital heart defects, are most often associated with a breakpoint proximal to 8p23.1. Three patients were found within a 3-year period in this study and five cases were found within 4 years by another group, indicating that distal 8p deletion might be a relatively common chromosomal abnormality. This small deletion is easily overlooked (i.e., cases 1 and 2 were reported as normal at amniocentesis) and can be associated with few or no major congenital anomalies. © 1996 Wiley-Liss, Inc.     

Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic? Observations in a four-generation kindred

Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal multiple congenital anomalies, but recurrence of this phenotype within one family has not been reported. Males with oto-palato-digital syndrome type II (OPD II) also demonstrate a multiple congenital anomalies phenotype that includes skeletal dysplasia but the maternal phenotype includes only mild craniofacial anomalies. These two syndromes have been suggested as being allelic despite differences in the described maternal phenotypes. We present a four-generation kindred in which four males had a consistent multiple congenital anomalies phenotype. The females in this family have skeletal changes characteristic of MNS but have only mild craniofacial anomalies and also deafness attributable to ossicular deformity, traits more commonly found in OPD II. The expression of manifestations of MNS and OPD II in males and females in this kindred further suggest that these syndromes are allelic. Am. J. Med. Genet. 71:341–347, 1997. © 1997 Wiley-Liss, Inc.     

Epidemiology of congenital hydrocephalus in Utah, 1940–1979: Report of an iatrogenically related “epidemic”

As part of an epidemiological study of congenital hydrocephalus in Utah, we focused on the effect of ascertainment sources and temporal variability to further delineate the causes of this relatively common, handicapping birth defect. The incidence and distribution of 934 reported cases diagnosed prior to age 6 months, and born to Utah residents from 1940 to 1979, were analyzed. Data were ascertained by examination of multiple sources, e.g., 982,066 birth, 11,161 fetal death, and 248,208 death certificates, and selected hospital and clinic records. Of the 934 reported cases, 700 met our selection criteria for congenital hydrocephalus, which results in a crude incidence of 0.70 per 1,000 live and stillbirths. Seventy-one cases (10.1%) had additional, multiple congenital anomalies. The male/female sex ratios of the 619 cases of isolated congenital hydrocephalus (occurring as a single entity or in the absence of other reported or known birth defects) and those with multiple congenital anomalies (71 cases) were virtually identical, being 1.45 and 1.48, respectively. A significant 85% increase in the rate of reported cases was observed for the period 1966 to 1970. However, examination of patients' records from 1966 to 1975 in the hospital responsible for almost all of this increase suggests that this was an iatrogenically related “epidemic” caused by several factors: the introduction and possible misinterpretation of pneumoencephalograms (PEG) in the diagnosis of hydrocephalus (PEG was replaced by CAT scanning in the early 1970s), inappropriate diagnosis, and incorrect recording of age at time of diagnosis. © 1994 Wiley-Liss, Inc.     

Severe acro-renal-uterine-mandibular syndrome

Although limb and renal defects occur together in a variety of patterns of multiple malformations, familial cases of acro-renal disorders are rare. In 1980, Halal et al. ?Am J Med Genet 5:277-284 described two sisters with unusual limb deficiencies, renal anomalies, and mandibular hypoplasia and termed this condition acro-renal-mandibular syndrome. A girl reported earlier by Fitch and Lachance ?1972; Can Med Assoc J 107:653-656 had similarly limb and renal findings, but an apparently normal jaw. We document three sibs with unusual limb deficiencies, renal agenesis, uterine anomalies in the two females, and orofacial defects, who clearly have a similar but more severe type of acrorenal disorder, apparently inherited as an autosomal recessive condition. The sibs with limb deficiencies and renal agenesis reported by Hennekam et al. ?1994; Am J Med Genet 53:102-107 appear to be additional cases of this very rare disorder, the pathogenesis of which may be related to abnormal epithelial-mesenchymal interactions.     

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.     

Descriptive epidemiology of Cornelia de Lange syndrome in Europe

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed 相似文献