Congenital Malformations in Autosomal Trisomy Syndromes

Abstract

ITHAS BEEN known since 1959 that certain chromosomal aberrations are associated with syndromes of congenital malformations; thus explanations have been found for many malformations which were previously enigmatic. It is understandable that in the resulting literature chromosome findings and cytogenetic details were stressed, while teratologic effects were often not sufficiently emphasized. It seems worthwhile and timely to relate the results of autosomal trisomy studies to classifications of pathology and teratology of the various organ systems.It will be of value to describe for the benefit of clinical specialists the varieties of malformations produced by certain chromosomal aberrations. The cardiologist will be interested to see tables comparing the effects upon the heart of trisomy 13-15 (D1), and trisomy 18 with those of trisomy 21, and to learn of their relative frequency and variability. The same may be true for the neurologist, ophthalmologist, orthopedic, pediatric and plastic surgeon, urologist, and others.We have reviewed the literature of the known autosomal trisomies, listing the mal¬ formations according to organ systems. For malformations of internal organs we have used preferably necropsy findings which permit satisfactory comparison of the symp¬ toms of trisomy 13-15 and 18, since the. affected patients rarely survive the first two years of life. This circumstance is not generally true for trisomy 21, which is essentially composed of two populations, one with a high mortality in the first year of life and another that survives infancy. It is clear that this dichotomy influences incidence figures and types of congenital malforma¬ tions, particularly those of the heart, which are much higher and more serious in the group with early mortality than in the sur¬ vivors. Survival of patients with trisomy 21 often poses the question whether all anomalies described in the literature of Down's syndrome are congenital or not.Anomalies of the brain or ocular lens re¬ ported as characteristic of the syndrome may in fact be secondary changes developing after birth on the basis of defective tissues. Other difficulties encountered were differ¬ ences in reporting and terminology. Some pathologists list single anomalies, eg, ven¬ tricular septal defect and pulmonic stenosis, separately, while others write summarily of tetralogy of Fallot or cushion defect. Simi¬ lar discrepancies have occurred in reports on anomalies of other organ systems.Although the manifestations of the triso¬ mies enumerated below show recurring types and patterns, they cannot be considered final and definitive as new reports appear with observations of additional symptoms. But the tabulations given below can serve as a framework to be revised and completed.Arbitrarily we have limited this review to "regular" autosomal trisomies and have ex¬ cluded all structural chromosome abnorDownloaded From: http://archpedi.jamanetwork.com/ by a University of Manitoba User on 06/04/2015

Mortality in Down’s syndrome in relation to congenital malformations

“…One may regard autopsy findings as the true reference of a malformation. The frequency of CHDs reported in the present study is comparable to that found in autopsy studies ( Warkany et al . 1966 ).…”

“…One may regard autopsy findings as the true reference of a malformation. The frequency of CHDs reported in the present study is comparable to that found in autopsy studies (Warkany et al 1966). The distribution of different congenital heart malformations displayed a well-known pattern with a predominance of AVSD (41.3%) and VSD (32.3%), and with PDA as the most common associated heart malformation (Rowe & Uchida 1961;Ferencz et al 1989) The overall cumulative mortality among the children with DS in the present study was 23.5% during the first 10 years of life and the number of children lost to follow-up was negligible.…”

Trisomy 18 in Greece

“…Most of our patients were born after a gestation of more than 40 weeks with a low birth weight (less than 2500 g). The average birth weight of our patients was 2 154 g, which agrees with the average weight (2 183 g) of 90 cases of trisomy 18 analysed by Warkany et al (10). found by Ferguson-Smith (4) and Weber (11).…”

Congenital heart anomalies in the trisomy 18 syndrome, with reference to congenital polyvalvular disease

“…Valvular anomalies included bicuspid aortic valve in 15 (18%), bicuspid pulmonary valve in 23 (28%), and other valvular anomalies in 16 (20%). Similar observations were also noted by Warkany et al [1966]. Bharati and Lev [1973] and Goto et a1 [1973] also described valvular anomalies in trisomy 18.…”