Mortality risks in patients with constitutional autosomal chromosome deletions in Britain: a cohort study

Constitutional chromosome deletions result in wide ranging morbidity and often fatality. Information about risks and causes of death in these patients is important for counselling, and may illuminate the functions of the part of the chromosome deleted. There have been no cohort studies analysing mortality risks in persons with specific deletions compared with general population rates. We therefore conducted a cohort study following cause-specific mortality in 2,561 patients with autosomal chromosome deletions diagnosed by light microscopy or fluorescence in situ hybridisation at cytogenetic laboratories across Britain, 1965–2002. The commonest deletions were of 22q (544 patients), 15q (460) and 7q (210) and the least common 19q (0) and 20q (2). The prevalence of visible deletions of different chromosome arms was significantly inversely correlated with gene density of the arm (p < 0.001). Mortality was 11-fold raised in the cohort compared with the general population (standardised mortality ratio = 11.4 (95% confidence interval 10.0–12.8)), was significantly raised for each deletion with ≥25 subjects in the study, and had a lower confidence limit >10 for deletions of 1p, 1q, 3p, 4p, 5q and 22q. Overall, 29% of deaths were due to congenital anomalies; significantly raised mortality occurred also from many other causes, varying by chromosome and arm of deletion. The data imply that viability of foetuses with visible chromosome deletions may be inversely related to gene density, and that all visible and fluorescence in situ hybridisation-detectable deletions lead to much raised mortality, but the extent and causes of mortality vary according to the specific deletion. The UK Clinical Cytogenetics Group comprises: The above, plus Paul J Batstone (Inverness Genetics Laboratory), Thomas Spencer (NE London Regional Cytogenetics Laboratory, Great Ormond Street Hospital), Teresa Davies (Bristol Genetics Laboratory), Valerie Davison (Birmingham Genetics Laboratory), Zoe Docherty (SE Thames, Guy’s Hospital Genetics Laboratory), David P. Duckett (Leicestershire Genetics Centre), Margaret Fitchett (Oxford Genetics Laboratory), Alison Fordyce (MRC Human Genetics Unit, Edinburgh); Lorraine Gaunt (Manchester Genetics Laboratory), Elizabeth Grace (Edinburgh Genetics Laboratory), Peter Howard (Liverpool Genetics Laboratory), Gordon W. Lowther (Glasgow Genetics Laboratory), Christine Maliszewska (Dundee Genetics Laboratory), Edna L. Maltby (Sheffield Genetics Laboratory), Kevin P. Ocraft (Nottingham Genetics Laboratory); Selwyn Roberts (Wales Genetics Laboratory), Kim K. Smith (Cambridge Genetics Laboratory), Gordon S. Stephen (Aberdeen Genetics Laboratory), John W. Taylor (SW Thames, St George’s Hospital Genetics Laboratory), Catherine S. Waters (NW Thames, Northwick Park Hospital Genetics Laboratory), Jeffery Williams (Leeds Genetics Laboratory), John Wolstenholme (Newcastle Genetics Laboratory), Sheila Youings (Wessex Regional Genetics Laboratory).