Changing Demography and Variable Expressivity in

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non-mosaic chromosome disorders compatible with postnatal ... ple organ defects and overwhelming infections.2,4−7 ... not all related to trisomy 13 mosaicism.
Pediatr Neonatol 2009;50(4):133−134

EDITO R IAL

Changing Demography and Variable Expressivity in Autosomal Trisomy Syndromes Jia-Woei Hou Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan

There are 23 pairs of human chromosomes. Any chromosome number that is not an exact multiple of the haploid number (i.e., n = 23 in humans) indicates aneuploidy. The common forms of aneuploidy in humans are trisomy (the presence of an extra chromosome) and monosomy (the absence of a single chromosome). There are only three, well-defined non-mosaic chromosome disorders compatible with postnatal survival in which there is trisomy for an entire autosome: Trisomy 21 (Down syndrome, the most common), trisomy 18 (Edwards syndrome, the second most common), and the rather rare, trisomy 13 (Patau syndrome).1−3 Each of these autosomal trisomies is associated with growth and mental retardation, and multiple congenital anomalies. The clinical features characteristic of any one trisomic state are determined by the extra dosage of the particular genes on the additional chromosome. Trisomies may also be present in mosaic form, with variable, but usually somewhat milder, expression or longer survival. Most autosomal trisomy syndromes are associated with increased maternal age, and the extra chromosome usually arises from nondisjunction occurring at maternal meiosis I. Prenatal ultrasound can detect many abnormalities. Karyotyping analysis following chorionic villus sampling or amniocentesis, or blood tests after birth, can confirm the diagnosis. Imaging studies such as ultrasound or magnetic resonance imaging of the heart and abdomen can also detect fetal abnormalities. Medical care for individuals with autosomal trisomies is supportive, and focuses on providing nutrition, treating infections, and managing organ abnormalities. Most mortality in patients

with Down syndrome occurs during the first year of life; the 1-year survival rate is 93.6%, indicating that the life expectancy in patients with trisomy 21 is much longer than generally believed.1 However, infants with trisomy 18 or 13 only have a 5−10% chance of surviving to age 1 year, probably because of the complex medical problems, including multiple organ defects and overwhelming infections.2,4−7 In the mean time, major medical or aggressive surgical interventions are often withheld from these children. Many factors have the potential to affect survival rates. In this issue of the journal, Hsiao et al8 report on their analysis of detailed data from 31 liveborn babies with Edwards syndrome. Early diagnosis, changes in medical management, and the family’s attitude are considered to be the major factors influencing survival. A recent report regarding the survival and natural history of trisomy 18 by Lin et al2 showed that the implementation of a National Health Insurance (NHI) program also facilitated longer survival in these patients. The degree to which essential organs are affected at birth and the clinical course differ considerably. Hsu and Hou3 found that most trisomy 13 patients were born to younger mothers who did not undergo amniocentesis, because no major anomalies except for cleft lip/palate were found on prenatal sonograms. The median survival time in their series was longer than that previously reported. A less severe course of autosomal trisomy syndrome can be caused by a partial trisomy, due to a deletion of the extra chromosome 18, or somatic mosaicism with a trisomic and a normal cell-line in the same patient. However,

Corresponding author. Department of Pediatrics, Cathay General Hospital, 280 Sec 4 Jen-Ai Road, Taipei 106, Taiwan. E-mail: [email protected] ©2009 Taiwan Pediatric Association

134 different outcomes in both clinical spectrum and survival have been reported in patients with trisomic mosaicism.3,9 Unlike trisomies 21 and 13, the preponderance of females with trisomy 18 among live-born infants (sex ratio, 0.63) compared with prenatally diagnosed fetuses (sex ratio, 0.90) indicates prenatal selection against males with trisomy 18 after the time of amniocentesis,10 or preferential survival of female fetuses. Trisomy 18 and trisomy 13 are associated with serious and/or fatal birth defects, many of which require surgical correction during the neonatal period. Difficult medical and ethical issues arise over whether or not to institute treatment when a newborn infant with autosomal trisomies has a lifethreatening anomaly. Improved survival through the advent of neonatal intensive care and NHI treatment allow clinicians to offer the best information on treatment options to the families of these patients.2,5,8 The chances of long-term survival can be increased by different expressivity after prenatal selection, as well as by cytogenetic mosaicism. Unknown genetic factors and various environmental effects are likely to be involved. In conclusion, the increasing utilization of prenatal diagnostic tools, earlier postnatal diagnosis, and advances in medical care, mean that the clinical presentations and survival patterns of autosomal trisomy syndromes have changed in recent decades. Accurate prognostic information, including the possibility of longterm survival, is crucial for allowing families to

J.W. Hou make the most appropriate decisions about further management.

References 1.

Hou JW, Wang TR. Mortality and survival in Down syndrome in Taiwan. Acta Paediatr Sin 1989;30:172−9. 2. Lin HY, Lin SP, Chen YJ, et al. Clinical characteristics and survival of trisomy 18 in a medical center in Taipei, 1988− 2004. Am J Med Genet 2006;140A:945−51. 3. Hsu HF, Hou JW. Variable expressivity in Patau syndrome in not all related to trisomy 13 mosaicism. Am J Med Genet 2007;143A:1739−48. 4. Goldstein H, Nielsen KG. Rates and survival of individuals with trisomy 13 and 18. Data from a 10-year period in Denmark. Clin Genet 1988;34:366−72. 5. Kosho T, Nakamura T, Kawame H, Baba A, Tamura M, Fukushima Y. Neonatal management of trisomy 18: clinical details of 24 patients receiving intensive treatment. Am J Med Genet 2006;140A:937−44. 6. Yamanaka M, Setoyama T, Igarashi Y, et al. Pregnancy outcome of fetuses with trisomy 18 identified by prenatal sonography and chromosomal analysis in a perinatal center. Am J Med Genet 2006;140A:1177−82. 7. Pont SJ, Robbins JM, Bird TM, et al. Congenital malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet 2006;140A:1749−56. 8. Hsiao CC, Tsao LY, Chen HN, Chiu HY, Chang WC. Changing clinical presentations and survival pattern of trisomy 18. Pediatr Neonatol 2009;50:147−51. 9. Tucker ME, Garringer HJ, Weaver DD. Phenotypic spectrum of mosaic trisomy 18: two new patients, a literature review, and counseling issues. Am J Med Genet 2007;143A:505−17. 10. Niedrist D, Riegel M, Achermann J, Rousson V, Schinzel A. Trisomy 18: changes in sex ratio during intrauterine life. Am J Med Genet 2006;140A:2365−7.