MONOZYGOTIC TWINS CONCORDANT FOR TRACHEO-ESOPHAGEAL FISTULA AND DISCORDANT FOR THE VATER ASSOCIATION

Abstract. Monozygotic female twins were concordant for tracheo-esophageal fistula (TEF); and one twin also manifested other anomalies of the VATER association, including agenesis of the female reproductive tract. Review of the literature discloses a familial tendency for recurrence of TEF and a high concordance rate in monozygotic twins, indicating a significant genetic influence for the isolated anomaly. In the case of the VATER association, the sporadic occurrence of affected individuals and discordance in twins implicates the effect of non-genetic factors.     

Hedgehog in the human: a possible explanation for the VATER association

Foregut malformations are relatively common anomalies, occurring in 1 in 2000-5000 live births. The adriamycin-induced rat model of the VATER association has provided a means of studying the morphogenesis of a variety of major congenital structural abnormalities similar to those seen in humans with VATER association. The secreted glycoprotein, Sonic hedgehog (Shh), may act as an endodermal signal that controls gut and lung patterning. Mice with targeted deletion of Shh have foregut defects that are consistent with those produced by administration of adriamycin. It is possible that mutations induced by adriamycin may result from the breakdown of the Shh signalling pathway.     

Amelia,hypoplasia of iliac bone,and absence of ischium and ramus pubis in the VATER association

A 1-day-old female presented with hypoplasia of the iliac bone and absence of the ischium and ramus pubis in the VATER association. To our knowledge, these skeletal anomalies have not been previously reported with the VATER association. Offprint requests to: M. Pul     

The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis

 The adriamycin-induced rat model of the VATER association has provided a means of studying the morphogenesis of a variety of major congenital structural abnormalities similar to those seen in humans with the VATER association. Most interest has been centered on the foregut, where the model has clarified some aspects of the development of esophageal atresia (EA), tracheal agenesis, and other communicating bronchopulmonary foregut malformations. It has demonstrated aberrations in the nerve supply to the esophagus in EA and allowed the study of tracheomalacia. A relationship between an abnormal notochord, foregut abnormalities, and vertebral defects has been shown, and the model has reignited interest in the role of the notochord as a regional organizer of axial development. The normal temporospatial characteristics of apoptosis during fore- and hindgut development is disturbed in this model, resulting in abnormal morphology. The indications are that this model will continue to clarify the processes that lead to many of the structural congenital abnormalities that are seen in infants born with the VATER association. Accepted: 19 January 2000     

PART II. BODY COMPOSITION OF THE MALE REFERENCE ADOLESCENT

Utilizing available data for total body water, total body potassium and total body calcium, fat and fat-free body mass (FFBM) of the reference male adolescent between 10.5 and 18.5 years has been estimated. FFBM was conceptualized to consist of water, protein, carbohydrate, osseous and nonosseous minerals. With increasing age, water concentration of FFBM decreases, protein concentration increases slightly and concentration of osseous minerals increases substantially. The combined effect of these changes is that density of FFBM increases with age. Osseous minerals increase mainly during the adolescent growth spurt. With the age and sex-specific FFBM: total body water ratios and densities of FFBM presented it will be possible to avoid systematic underestimation of fat content from measurements of total body water and overestimation of fat content from determinations of body density by underwater weighing.     

THE RADIAL DYSPLASIA/IMPERFORATE ANUS/VERTEBRAL ANOMALIES SYNDROME (THE VATER ASSOCIATION): DEVELOPMENTAL ASPECTS AND EYE FINDINGS

Abstract Say, B., Greenberg, D., Harris, R., DeLong, S. L. and Coldwell, J. G. (Department of Developmental Medicine & Child Neurology, Children's Medical Center, Tulsa, Oklahoma, USA). The radial dysplasia/imperforate anus/vertebral anomalies syndrome (the VATER association): developmental aspects and eye findings. Acta Paediatr Scand 66: 233, 1977.—The developmental evaluations of four children of different age groups with radial dysplasia/imperforate anus/vertebral anomalies syndrome are presented. These show that although the gross motor behavior is significantly delayed, intelligence, language, and social development are within normal range. Therefore, the patients with this syndrome merit every effort toward rehabilitation. Three of the patients discussed have ophthalmological abnormalities, in addition to their major malformations. It may be that congenital eye defects are another component of this syndrome of morphogenesis.     

EXTRASKELETICAL MALFORMATIONS IN THE JARCHO-LEVIN SYNDROME: POSTMORTEM STUDY OF THREE CASES

We report on pathologic examination of three autopsied newborns with Jarcho-Levin syndrome. The most important abnormalities noted were multiple extraskeletical defects such as cardiovascular, urogenital, respiratory, and central nervous system malformations. These cases add new information to the multiple vertebral segmentation defects found in this syndrome.     

Switched-on Sonic hedgehog: a gene whose activity extends beyond fetal development--to oncogenesis

Embryonic and fetal development is a highly complex process choreographed by several families of genes that regulate early development of the embryo. Disruption in the structure and/or function of developmental genes produces morphogenic errors of development. One such family is the Hedgehog (Hh) signalling pathway, which plays an important role in the embryonal development of both invertebrates and vertebrates, including normal development of the brain, eye, limbs, foregut and its derivatives. Disruption of the Sonic hedgehog expression during critical periods of development is associated with developmental disorders of the brain, namely, holoprosencephaly, and the VATER association. Inappropriate activation of the pathway in post-embryonic development has been demonstrated in several human malignancies, including those of the brain and skin, both in children and adults. Specific inhibition of Hh signalling in these tumours inhibits growth of a wide range of malignancies. This demonstrates a requirement for Hh signalling in these tumours. These observations suggest that a better understanding of the genetic control of morphogenesis can ultimately provide us with greater knowledge of how congenital structural abnormalities occur, as well as the processes that lead to several childhood and other tumours. There may be a closer relationship between embryogenesis and oncogenesis than previously realised.     

CROHN'S DISEASE OF THE PREPUCE IN A 12-YEAR-OLD BOY: A Case Report and Review of the Literature

We report a case of Crohn's disease with involvement of the foreskin in a 12-year-old boy. One year previously, on the basis of clinical features (diarrhea with blood, perianal fissures) and histologic examination, a diagnosis of Crohn's disease was made. Subsequently, he developed phimosis and balanitis and underwent circumcision. Sections submitted from the foreskin revealed noncaseating granulomatous inflammation consistent with Crohn's disease. Crohn's disease with involvement of the genitalia is unusual. Only 26 cases including our case have been reported in the scientific literature. We have analyzed these cases with emphasis on gender, age, clinical features, duration of Crohn's disease, and probable mode of spread to the genitalia. Careful examination of sections from genital lesions, including those submitted from the foreskin, is essential to detect small isolated granulomas that may then lead to the diagnosis of inflammatory bowel disease.     

SEASONAL INCIDENCE OF SOME CONGENITAL MALFORMATIONS IN THE CENTRAL NERVOUS SYSTEM IN SWEDEN, 1965–1972

Abstract Seasonal trends of some congenital CNS malformations in infants born in Sweden during the years 1965 to 1972 were investigated. The study is based on reports to the Swedish Register of Congenital Malformations, statistics from the National Board of Health, and records from Malmö General Hospital and the Hospital of Lund. The malformations analysed in this study are anencephaly, spina bifida aperta (with or without hydrocephalus) and isolated hydrocephalus. Variations in incidence of months of birth and last menstrual period (LMP) were tested statistically in three different ways: standard χ²-test for heterogeneity between recorded numbers of infants each calender month, Edwards' method, and a squared sinus function, all with or without correction for variations in genera) monthly birth rates. Statistical significant seasonal variations were found for anencephaly with an LMP maximum in March and for spina bifida aperta with a maximum in July. Factors which can explain such seasonality are briefly discussed.     

THE ASSOCIATION OF LEUKOCYTE ADHESION DEFECT TYPE I AND PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY IN A SAUDI ARABIAN FAMILY

The authors describe 2 female sibling infants diagnosed with leukocyte adhesion defects CD11 and CD18. Both had successful bone marrow transplants from identical siblings. One of the patients was found to have persistent hypoglycemia of infancy. The association of these two rare conditions has not been reported previously.     

CRANIAL MR VENOGRAPHY FINDINGS OF SEVERE HYPERNATREMIC DEHYDRATION IN ASSOCIATION WITH CEREBRAL VENOUS THROMBOSIS IN THE NEONATAL PERIOD

Severe neonatal hypernatremia is an important electrolyte disorder that has serious effects on the central nervous system, including brain edema, intracranial hemorrhage, hemorrhagic infarct, and thrombosis. Cerebral venous thrombosis is relatively rare in severe neonatal hypernatremic dehydration. The English literature contains only a few reports of the cranial radiological findings in severe neonatal hypernatremia. The authors report cranial MR venography findings of a newborn infant with severe hypernatremic dehydration. To the best of their knowledge, this is the first such report in the English literature.