DE NOVO INTERSTITIAL DELETION OF THE LONG ARM OF CHROMOSOME 2 IN A MALFORMED NEWBORN WITH A KARYOTYPE: 46, XY, del(2)(q12q14)

ABSTRACT. A male neonate with severe malformations, including facial dysmorphism, a short neck, postaxial-hexadactyly of the toes, congenital herat disease, hydronephrosis, imperforate anus and agenesis of corpus callosum, is described. His karyotype was 46, XYdel(2)(q12q14).     

Congenital Malformations: A Review of 672 Autopsies in Ibadan, Nigeria

The postmortem findings in 672 Nigerian children with lethal congenital malformations are reviewed. Eighty-six percent of the patients were less than 1 year of age and the male-to-female sex ratio was 1.3:1. The alimentary tract was the most common anatomic site involved (30%), intestinal and biliary atresia being the two lesions most frequently identified in this location. Twenty-six percent of the children had cardiovascular malformations, of which ventricular septal defect, patent ductus arteriosus, and tetralogy of Fallot were most important. There was an accentuated male predominance among cases with urogenital malformations due to the high frequency of posterior urethral valve. Hydrocephalus, spina bifida, and anencephaly were the most common lesions observed in the craniospinal axis. One-fifth of the children had complex malformations of multiple organ systems, 20% of which were associated with chromosomal anomalies, rubella, and other malformation syndromes.     

Gastrointestinal malformations in Gorgan,North of Iran: epidemiology and associated malformations

The aim of this prospective study was to evaluate the prevalence and pattern of gastrointestinal malformations (GIM) among Iranian newborns in Gorgan, North of Iran. From 1998 through 2003, 37,951 live births in Dezyani hospital in Gorgan, North of Iran, were screened for gastrointestinal malformations. Clinical and demographic factors of diagnosed cases were recorded in a pre-designed questionnaire for analysis; sex, ethnicity, type of GIM and associated anomalies. The overall prevalence rate of gastrointestinal malformations was 10 per 10,000 births. The imperforate anus (5 per 10,000) was the commonest birth defect in gastrointestinal tract. The prevalence rate of GIM was 8.2 per 10,000 in males and 10.7 per 10,000 in females. According to the parental ethnicity, the prevalence rates of GIM were 6.7, 15.8 and 17.6 per 10,000 in Fars, Turkman, and Sistani, respectively. There were eight cases (21%) with associated anomalies. The prevalence rate of GIM in North of Iran is not similar to the previous studies in Iran and Middle East and ethnic background may be a causative factor in the rate of GIM in this area.     

Doppler Evaluation of Atrial Septal Defect, Ventricular Septal Defect, and Complex Malformations

ABSTRACT. The Doppler approaches, accuracy, pitfalls and quantitation of atrial and ventricular shunts are reviewed. For both levels of shunting, Doppler demonstration of flow through the septum confirms the diagnosis and directional flow information may provide physiologic information. Shunt sizes may be measured directly by Doppler, and should be reflected by chamber dimensions and volumes. The flow disturbances present in complex malformations such as Ebstein's malformation, transposition of the great arteries with ventricular septal defect, atrial shunting before and after balloon atrial septostomy, total anomalous pulmonary venous return, closely related high velocity flows and coarctation are described. A sequential approach to each anomaly allows one to evaluate each, even if multiple defects are combined in a given patient.     

Signaling regulating inner ear development: Cell fate determination,patterning, morphogenesis,and defects

The membranous labyrinth of the inner ear is a highly complex organ that detects sound and balance. Developmental defects in the inner ear cause congenital hearing loss and balance disorders. The membranous labyrinth consists of three semicircular ducts, the utricle, saccule, and endolymphatic ducts, and the cochlear duct. These complex structures develop from the simple otic placode, which is established in the cranial ectoderm adjacent to the neural crest at the level of the hindbrain at the early neurula stage. During development, the otic placode invaginates to form the otic vesicle, which subsequently gives rise to neurons for the vestibulocochlear ganglion, the non‐sensory and sensory epithelia of the membranous labyrinth that includes three ampullary crests, two maculae, and the organ of Corti. Combined paracrine and autocrine signals including fibroblast growth factor, Wnt, retinoic acid, hedgehog, and bone morphogenetic protein regulate fate determination, axis formation, and morphogenesis in the developing inner ear. Juxtacrine signals mediated by Notch pathways play a role in establishing the sensory epithelium, which consists of mechanosensory hair cells and supporting cells. The highly differentiated organ of Corti, which consists of uniformly oriented inner/outer hair cells and specific supporting cells, develops during fetal development. Developmental alterations/arrest causes congenital malformations in the inner ear in a spatiotemporal‐restricted manner. A clearer understanding of the mechanisms underlying inner ear development is important not only for the management of patients with congenital inner ear malformations, but also for the development of regenerative therapy for impaired function.     

Prenatal diagnosis of a probable hereditary syndrome with holoprosencephaly,hydrocephaly, octodactyly,and cardiac malformations

Following genetic counselling of a consanguineous couple because of a daughter born with peripheral hypoplasia of the left arm, ultrasonographic examination during the second pregnancy revealed marked hydrocephalus of the fetus in the 17th week of pregnancy. Pathologic examination of the female fetus disclosed severe cerebral, cardiac, and skeletal malformations including holoprosencephaly, absent corpus callosum, microphthalmia, facial clefts, tetramelic octodactyly, and cardiac defects. These findings indicate a possible genetically determined syndrome that appears to be distinct in spite of some overlap with other malformation syndromes.     

Cardiac Abnormalities and Nonimmune Hydrops Fetalis: a Coincidental, Not Causal, Relationship

Few conditions associated with nonimmune hydrops fetalis have had a demonstrable causal relationship. Congenital heart disease is often said to be a cause of nonimmune hydrops fetalis and antenatal closure of the foramen ovale is the cardiac abnormality most frequently reported in association with hydrops. In order to examine the role of congenital heart disease in hydrops, and, in particular, that of antenatal closure of the foramen ovale, we reviewed all autopsy cases with hydrops fetalis over an 11 year period and compared cardiac anomalies with those of nonhydropic controls. The incidence of various congenital heart malformations was not significantly different among these groups, suggesting that factors in addition to cardiac anomalies must be considered in the pathogenesis of nonimmune hydrops fetalis.     

Profile of major congenital malformations at Nizwa Hospital, Oman: 10-year review

OBJECTIVE: The objective of this study was to establish the profile of major congenital malformations at Nizwa Hospital, which is a major hospital in the Al-Dakhliya region of Oman. METHODS: All births with birthweight more than 500 g were prospectively studied from January 1993 through December 2002 for a period of 10 years. A congenital anomaly register was maintained in the special care baby unit (SCBU) and details of each case were recorded after parents' interviews, clinical evaluation and relevant radiological and laboratory investigations. The major malformations were classified as multiple or single-system abnormalities as well as genetic or non-genetic disorders. RESULTS: Of the 21 988 births during the study period, 541 babies (24.6 per 1000 births) had major malformations. Of the 541 babies, 158 (29.2%) had multiple malformations and 335 (61.9%) had involvement of a single system. In 48 (8.9%) babies a complete evaluation was not possible. Of the cases with multiple abnormalities, 57 had recognized syndromes, of which 28 (49.1%) were autosomal recessive disorders. Seventy (12.9%) cases had chromosomal abnormalities. The most common systems involved in neonates with single-system malformations were the gastrointestinal system (100 cases), the central nervous system (79 cases) and the cardiovascular system (63 cases). Although the consanguinity rate of 53.1% among Omani births almost matched with the regional average of 52.7%, it was 76% among those with major malformations. Also, there was an increased clustering of multiple abnormalities and rare recessive disorders in cases with closely related parents and grandparents. The birth prevalence of major malformations was 14.6 per 1000 in non-Omani births as compared to 25.2 in Omani births (P < 0.05). Genetic factors could be implicated in 343 (63.4%) cases and 130 (37.9%) of these were potentially preventable. CONCLUSION: Genetic disorders account for a significant proportion of congenital malformations in Oman.     

The Genetics of Hand Malformations: Updated*

Abstract The main values of our knowledge of the genetics of birth defects are proper diagnosis and counseling. A classification of hand malformations on anatomic and genetic grounds was proposed by Temtamy (1966), Temtamy and McKusick (1969, 1978): The ten main categories are (1) Absence, (2) Brachydactyly, (3) Syndactyly, (4) Polydactyly, (5) Symphalangism, (6) Arachnodactyly, (7) Macrodactyly, (8) Carpal/Tarsal synostosis, (9) Congenital ring constrictions, and (10) Contractures. The hand malformation is either isolated or associated with other organ malformation as a part of syndromes. In the monograph by Temtamy and McKusick (1978), numerous new syndromes were identified, some of which were based on single or few observations. The paper summerizes the pertinent findings in a computerized literature survey of absence or deficiency malformation as part of synderomes reported between 1977 and 1983. Analysis of the literature confirmed the identity of previously reported syndromes and added “new” entities. The originally proposed classification of hand malformations proved to be useful and allowed for easy sorting out of the recent literature and for indentification of new syndromes.     

Exposure to Ethylnitrosourea Before Implantation Induces Congenital Malformations in Mouse Fetuses

Abstract The effects of ethylnitrosourea (ENU) on the development of preimplantation mouse embryos were investigated. ICR mice were treated intraperitoneally with single doses of 25, 50 or 100 mg ENU/kg body weight on day 0, 1, 2 or 3 of gestation, or with single doses of 25, 50 or 75 mg ENU/kg on day 8 of gestation. The uterine contents were examined on day 18 of gestation, and viable fetuses were inspected for external and skeletal malformations. No significant differences were observed in the number of implants between the ENU-treated groups on day 1, 2 or 3 of gestation and controls, while the number of implants in all of the groups treated with ENU on day 0 of gestation was significantly decreased compared to that in the control group. The frequencies of early postimplantation deaths were significantly increased in all of the groups treated with ENU on each gestational day before implantation, compared to the control frequencies. ENU treatment before implantation caused dose-dependent increases in the incidence of externally or skeletally malformed fetuses. Cleft palate, exencephaly and umbilical hernia were the most common types of external malformations in the groups treated with ENU before implantation and in the control group. The skeletal malformations seen in the ENU-treated groups were malformed vertebrae, malformed ribs, and bending of appendicular skeleton. Fused ribs was the most common skeletal malformation seen in the control fetuses. The type distributions of external and skeletal malformations induced by the treatment with ENU before implantation is quite different from those of fetal malformations induced by the treatment with ENU at the organogenesis stage. The results in the present study demonstrate that embryos before implantation in the uterus are susceptible with regard to the induction of congenital malformations by chemicals, and I propose that a large portion of the external malformations in fetuses treated at the preimplantation stages is the result of increased yields of spontaneously-occurring malformations.     

Congenital heart defects--chromosomal anomalies, syndromes and extracardiac malformations

AIM: To register chromosomal anomalies, syndromes and extracardiac malformations in patients with Congenital heart defects (CHDs). METHOD: Population-based prospective observational study. RESULTS: Of 57 027 live births during 1982-2005, CHDs were detected in 662 (11.6 per 1000), of whom 146 (22%) had associated anomalies. Of these 52 (36%) had chromosomal anomalies (exclusive microdeletions), 26 (18%) genetic syndromes/microdeletions, 1 (0.7%) a teratogenous syndrome and 67 (46%) extracardiac malformations. In perimembraneous ventricular septal defects (VSDs), associated anomalies occurred in 22 of 70 (31%) compared to 27 of 298 (9%) in VSDs located in the muscular part of the septum (p < 0.0001). The prevalence of CHDs with associated disorders increased significantly from the cohort born during 1982-1993 to those born during 1994-2005 (2.0 vs. 3.1 per 1000, respectively; p < 0.0001), mainly caused by an increase of chromosomal trisomies (0.5 vs. 1.1 per 1000; p = 0.026). The percentage of women giving live birth at 35 years of age or more was 7.6% for the period 1982-1993 compared to 13.4% for 1994-2005 (p = 0.001). CONCLUSIONS: Chromosomal anomalies, syndromes and extracardiac malformations occurred in nearly one-fourth of CHD cases. Muscular VSDs had a low prevalence of such conditions. The prevalence of CHDs with chromosomal trisomies increased, and was probably related to an increasing age of women giving birth.     

The role of colostomy in the management of anorectal malformations

The role of the colostomy in the definitive correction of anorectal malformations is controversial with regard no only to indications for its use, but also to location and type. We reviewed the records of 272 patients with 307 colostomies and analyzed the frequency of complications related to these controversial points. There were 250 completely divided and 57 loop colostomies, constructed in either the sigmoid or transverse colon. Twenty-five colostomies were associated with complications that included retraction, stenosis, dehiscence, prolapse, infection, bowel obstruction, sepsis, and death. Twelve additional colostomies were placed in positions that impeded the definitive correction of the malformation: 9 sigmoidostomies were too distal and 3 were located in the right-upper abdominal quadrant and did not permit pull-through without tension. Colostomy prolapse and pull-through infection were statistically less likely with a completely diverting colostomy. Thirty-five patients with rectovestibular malformations were encountered in this series. Ten were referred from other institutions after attempted repair without a colostomy and all 10 had complications of infection, dehiscence, retraction, and reopening of the fistula. In contrast, there were no complications in the remaining 25, in whom the repair was preceded by a colostomy, nor after re-repair of the other 10. These findings support the need for a colostomy prior to the repair of this malformation. We recommend a carefully constructed, high, completely diverting sigmoid colostomy prior to the initial definitive repair of anorectal malformations. A right transverse colostomy is preferable preceding redo operations.     

Definition of congenital malformations and detection of associations with maternal factors

Data collected from a cohort of 2913 pregnancies were analyzed to determine whether the varying definitions of congenital malformations influence the statistical result in the search for possible etiological factors. According to three different definitions of congenital malformations, three study groups were formed, i.e. structural malformations, all congenital defects, and all disorders or abnormalities with possible prenatal etiology. These consisted of 93, 197 and 334 cases, respectively. The control group consisted of 2579 cases. Positive associations were noted between the study groups and some factors concerning pregnancy, and the social history of the parents. The associations were strongest in the group of structural malformations and became weaker when this group was 'diluted' by other defects with questionable prenatal origin. Hence, when comparisons for evaluating the causality of significant associations in different materials are made, the definition of the concept of congenital malformations should be taken into consideration.     

Case Report of a 22-Week Fetus with 47,XXX Karyotype and Multiple Lower Mesodermal Defects

A 22-week stillborn fetus with 47,XXX karyotype had lower mesodermal defects consisting of irregular fusion of the sacral vertebrae, anal agenesis, multicystic dysplasia of a horseshoe kidney, a single umbilical artery, dysplastic ovaries, and uterine hypoplasia. This case provides additional evidence for an association between trisomy X and genitourinary defects including lower mesodermal defects sequence. Received November 21, 1997; accepted April 2, 1998.     

Urogenital function after cloacal reconstruction,two techniques evaluated

ObjectiveCurrent surgical techniques for cloacal reconstruction are posterior sagittal anorecto vagino urethroplasty (PSARVUP) and posterior sagittal anorectoplasty (PSARP) with total urogenital mobilization (TUM). The aim of this study was to explore the results of reconstructive cloaca surgery in the Netherlands and evaluate urogenital function after PSARVUP and TUM.Patients and methodsMedical records from five pediatric surgical departments in the Netherlands were studied for patients with cloacal malformations treated between 1985 and 2009. Forty-two patients were eligible, and patients with short common channels were categorized into PSARVUP and TUM groups. Groups were compared using Fisher's exact test.ResultsMedian age at time of surgery was 9 months (range 1–121). In 24 patients (57%) a PSARVUP was done, in 18 patients (43%) TUM. Median follow-up was 142 months (range 15–289). At follow-up spontaneous voiding was seen in 29 patients (69%). Clean intermittent catheterization (CIC) was needed in 14 patients (33%); a urinary diversion was created in 10 patients (24%). In total 32 patients (76%) were dry with no involuntary loss of urine per urethra. Recurrent urinary tract infections were seen in 23 patients (55%). When comparing PSARVUP and TUM groups in our series of patients with short common channels, there were no differences in urological outcome. Normal menstruation was present in 11 of the 20 patients who reached puberty (55%).ConclusionUrogenital functional outcome after reconstructive surgery for cloacal malformations was similar in PSARVUP and TUM groups in patients with short common channels. A thorough urological follow-up is needed to establish the long-term bladder function and urinary incontinence results to prevent long-term risks of recurrent UTI. Albeit without differences between PSARVUP and TUM groups, 45% of the patients present with abnormal or absent menstruations. Gynecological follow-up is mandatory in all patients with cloacal malformations 6 months after the first sign of puberty.     

Congenital Malformations and the Environment

Rokicki, W., Latoszkiewicz, K. and Krasnodehski, J. (Department of Paediatric Cardiology, Silesian Medical School, Katowice, Poland). Congenital malformations and the environment. Acta Paediatr Scand Suppl 360: 140, 1989.
The aim of the work was to search for the correlation between the environmental pollution and the ratio of congenital malformations found in the population of 54 493 newborn infants of three Silesian towns: Bielsko-Biala (situated in the mountains, close to a recreation part of the country), Bytom (situated in the center of an old industrial district, where industry is responsible for very high environmental pollution), and Tarnowskie Gory (situated close to vast woodlands, where very high environmental concentration of heavy metals is caused by an outdated, big zinc plant). In spite of big differences of environmental pollution indices between the three towns, the percentage of major congenital malformations diagnosed within the first three days of extrauterine life was almost identical (1.12% in Bielsko-Biala, 1.3% in Bytom, and 1.1 % in Tarnowskie Gory).     

Prevalence,treatment, and outcome of heart disease in live-born children: A prospective analysis of 91,823 live-born children

Summary All 91,823 children born in 1980 in Bohemia (population 6.314 million; area 52,478 square kilometers) were examined at least four times during infancy and at the age of three and four years. All children who died were autopsied and those with heart disease were selected. A total of 779 children (8.223/1000 live births) were suspected by provincial pediatric cardiologists of having a heart disease. All of these were examined at the age of four years at our Center of Pediatric Cardiology. At this age heart disease was proved in 613 alive or decreased children (6.676/1000 live births), congenital cardiac malformations in 589 (6.415/1000 live births), and cardiomyopathies in 24. The most frequent congenital heart defects (CHD) were ventricular septal defect (VSD) (31.41%), atrial septal defect (ASD) (11.37%), aortic stenosis (AS) (7.64%), pulmonary stenosis (PS) (7.13%), coarctation of the aorta (CoA) (5.77%), and transposition of the great arteries (TGA) (5.43%), followed by persistent ductus arteriosus (PDA) (4.75%), atrioventricular septal defect (AVSD) and hypoplastic left heart syndrome (HLHS) (4.07% each), tetralogy of Fallot (TF) (3.56%), and pulmonary atresia (PA) (2.38%). A prevalence of less than 0.1/1000 live births was found for the remaining cardiovascular defects.One hundred fifty-nine (25.9%) patients were admitted to our highly specialized center, 116 (19.7%) catheterized and 85 (13.9%) treated surgically, during the first four years of life. A total of 440 (71.8%) patients survived the fourth year of life. The percentage of deaths was 25.6% among those with congenital heart diseases and 71% with cardiomyopathies. The overall mortality rate was 27% in surgically and 26% in medically treated patients.     

PRIMARY HYPOTHYROIDISM, GROWTH HORMONE DEFICIENCY AND CONGENITAL MALFORMATIONS IN A CHILD WITH THE KARYOTYPE 46, XY, del(l)(q25q32)

Abstract. Primary thyroidal hypothyroidism, growth hormone deficiency, congenital malformations and mental retardation occurred in a child with an interstitial deletion of one of the No. 1 chromosomes. Two bands were missing, so that the karyotype could be written: del(l)(pter→q25::q32→qter). The possible relationship between the clinical features and chromosomal deletion are discussed.     

Branchio-Oto-Renal (BOR) syndrome: variable expressivity in a five-generation pedigree

A five-generation family with the branchio-oto-renal (BOR) syndrome is reported demonstrating the great variability of this syndrome. Symptoms of the branchio-oto, branchio-oto-ureteral, and BOR syndromes are seen in different members of this family, suggesting that these are not real entities, but variants of the BOR syndrome.