Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations at the PKD1 locus in most families. This locus has been assigned to the short arm of chromosome 16 by linkage analysis. It has been estimated that approximately 5% of families have a disease that does not map to this locus and most of these families have clinical features indistinguishable from the disease caused by PKD1 mutations. We report a large three-generation Caucasian family from Northern Ireland with ADPKD in whom all affected individuals (age range 22–68) were normotensive and only the two eldest had mild renal impairment. Linkage was excluded between the disease and both the alpha-globin gene complex and the microsatellite marker D16S283. This family confirms that phenotypic heterogeneity exists between unlinked families and that certain non-PKD1 mutations cause mild disease expression. Many such individuals may therefore remain undetected and the incidence of families with ADPKD who have non-PKDl mutations may be greater than previously estimated.
3 healthy women aged 35 22 and 28 years developed intravascular thrombosis while receiving oral contraceptive therapy (Case 1 took Anovlar for 1 years Case 2 took Conovid for 18 months and Case 3 took Enovid for 1 month). Cases 2 and 3 had chest lesions and were treated as pulmonary embolic disease. Case 1 was fatal and directs attention to the possibility that arterial thrombosis (in this case carotid) may also exist in addition to the more thrombophlebitis of the legs and pulmonary embolism.
P.J. Morrison, C.M. Steel, H.F.A. Vasen, D. Eccles, D.G.R. Evans, P. Moller, S. Hodgson, D. Stoppa-Lyonnet, J. ChangClaude, M. Caligo, E. Olah, N.E. Haites and N.C. Nevin Northern Ireland Regional Medical Genetics Centre, Belfast City Hospital Trust, Belfast, BT9 7AB, UK School of Biomedical Sciences, University of St. Andrews, Scotland, UK Foundation for the Detection of Hereditary Tumours, c/o University Hospital, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands Department of Human Genetics, Princess Ann Hospital, Southampton SO16 5YA, UK Department of Medical Genetics, St Mary’s Hospital, Manchester, UK Unit of Medical Genetics, The Norwegian radium Hospital, N-0310 Oslo, Norway Division of Medical and Molecular Genetics, Guy’s Hospital, London Bridge, London SE1 9RT, UK Unite de Genetique Oncologique Institut Curie Section Medicale 26, rue d’Ulm 75231 Paris Cedex 05 France Division of Epidemiology, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany Institute of Pathology, University of Pisa, via Roma, 57,56126 Pisa, Italy
Congenital atresia of the larynx is a rare abnormality. We describe three cases where prenatal diagnosis during the second trimester showed massive abdominal fetal ascites and at post-mortem, laryngeal atresia was identified in two cases, and severe laryngeal stenosis in the third. All were associated with pulmonary hyperplasia. No additional abnormalities were found in other systems. Overdistended lung tissue and ascites are resultant from aberrant laryngeal growth; laryngeal anomalies are a cause of isolated fetal ascites. The association of ascites and voluminous lungs should arouse suspicion of laryngeal atresia and should be an indication for careful pathological study of the fetal larynx.
OBJECTIVES To investigate a reported cluster of Down's syndrome in offspring of former pupils of a girls' school in Ireland, to establish the prevalence of Down's syndrome among live births in the area around the school, and to review the literature on the possible causes of reported clusters of Down's syndrome. METHODS Questionnaire survey of obstetric and personal histories of women who had attended the girls' school at Dundalk, County Louth, Republic of Ireland, at some time during 1956–7, and also of women who had attended another, nearby, girls' school during the same period. Comparison of observed numbers of cases of Down's syndrome identified by these surveys with maternal age adjusted expected numbers for the reported live births. Laboratory tests were conducted to verify and characterise the cases of Down's syndrome constituting the cluster. Retrospective collection and collation of data on Down's syndrome occurring among live births, and the compilation of maternal age specific incidences, in County Louth and in Newry and Mourne District in neighbouring Northern Ireland, during 1961–80. These rates were compared with reference rates and rates for other areas of Ireland. RESULTS Six children with Down's syndrome were confirmed among 387 reported live births to women who had been pupils at the girls' school in Dundalk during 1956–7, compared with 0.69 expected (nominal p<10 -4 ). Five of the affected births were to mothers under 30 years of age, against 0.15 expected (nominal p<10 -6 ), although only four of these mothers were attending the school at any one time. The origin of the non-disjunction was found to be maternal first meiotic in four children, mitotic after fertilisation in another (with the youngest mother), and in the remaining one could not be determined. The marked excess of Down's syndrome in births to young mothers did not extend to offspring of former pupils of the other Dundalk girls' school surveyed, or to live births in County Louth generally or in adjacent Newry and Mourne District. CONCLUSION A striking, highly localised, excess of Down's syndrome in births to young mothers who had attended a girls' school in Dundalk during 1956–57 has been confirmed. However, not all of the mothers of the affected children attended the school concurrently and the origin of non-disjunction in one child was an error occurring after conception. Some exposure essentially confined to girls attending the school at this time is a possible, although unlikely, explanation, but a review of potential risk factors does not suggest what this could be. Previous suggestions that an influenza epidemic or contamination from the Windscale nuclear reactor fire might be implicated, both of which occurred in October 1957, can be effectively dismissed because three of the women with affected offspring had left the school by then and had moved away from Dundalk, and Down's syndrome in the child of another mother originated in an error after fertilisation. Owing to the retrospective nature of the investigation and the characteristics of the cases, chance is the most likely explanation for the cluster.
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