Trisomy and Trisomy Disorders

Trisomy is the presence of three copies of a particular chromosome instead of the usual two, giving a chromosome count of 47 in an otherwise diploid cell. It is the most clinically important pattern of aneuploidy in humans: most autosomal trisomies are lethal in early development, but trisomies of chromosomes 21, 18, and 13, and trisomies of the sex chromosomes, are seen in liveborn children and define recognisable syndromes.

Definition

A trisomy is an aneuploid state in which one specific chromosome is present in three copies rather than two, so that the affected cell carries one extra chromosome (47 in a diploid background) and a corresponding excess of the genes on that chromosome.

Scope

The topic covers the concept of a single extra chromosome, the meiotic errors that produce it, the distinction between full, mosaic, and translocation forms, and the principal liveborn trisomy syndromes — Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13) — together with the common sex-chromosome trisomies. It is a reference description of these entities and their biological basis, not clinical management guidance.

Core questions

• Which trisomies are compatible with live birth, and why are these the exception rather than the rule?
• How do full, mosaic, and translocation trisomies differ in origin and in expected phenotype?
• Why does the risk of trisomic conceptions rise with maternal age?
• How does dosage imbalance of a whole chromosome translate into a developmental syndrome?

Key concepts

• Full trisomy (47 chromosomes)
• Mosaic trisomy
• Translocation (Robertsonian) trisomy
• Meiosis I versus meiosis II nondisjunction
• Gene dosage imbalance
• Trisomy 21 (Down syndrome)
• Trisomy 18 (Edwards syndrome)
• Trisomy 13 (Patau syndrome)
• Sex-chromosome trisomy

Mechanisms

A trisomy most often results from nondisjunction during meiosis, when a chromosome pair or sister chromatids fail to separate and a gamete receives an extra chromosome; fertilisation then yields a zygote with three copies. The error occurs preferentially in maternal meiosis I and rises in frequency with maternal age. Trisomy can instead arise post-zygotically in mitosis, producing a mosaic of trisomic and normal cells, or from a Robertsonian translocation, in which the extra chromosomal material is attached to another chromosome and can be transmitted by a balanced carrier parent. In every form the shared consequence is a 50 percent excess dosage of the genes on the trisomic chromosome, which perturbs development to a degree that depends on which chromosome and which genes are involved.

Clinical relevance

Trisomies account for the most frequently recognised autosomal chromosome disorders in liveborns and are a major target of prenatal screening and diagnosis. This entry describes the biology and clinical features of these syndromes as reference material for evidence appraisal; it does not provide diagnostic or treatment recommendations for any individual.

Epidemiology

Most autosomal trisomies are incompatible with survival and are common findings in spontaneous miscarriage. Among liveborns, trisomy 21 is the most frequent and shows the strongest maternal-age dependence; trisomy 18 and trisomy 13 are rarer and associated with high early mortality, with most affected infants surviving only briefly, as documented in natural-history series. Sex-chromosome trisomies are collectively common and frequently have milder or subtle phenotypes.

History

Trisomy 21 was the first chromosomal disorder identified in humans, recognised in 1959 as the cause of Down syndrome, and trisomy 18 and trisomy 13 were described as distinct syndromes shortly afterwards. These discoveries established that an extra whole chromosome could cause a defined clinical condition and launched clinical cytogenetics; later work clarified the meiotic origin of the extra chromosome and the maternal-age effect.

Key figures

• Jerome Lejeune
• John Hilton Edwards
• Klaus Patau
• Terry Hassold

Seminal works

• roizen-patterson-2003
• cereda-carey-2012
• hassold-hunt-2001

Frequently asked questions

Why are trisomy 21, 18, and 13 the trisomies usually seen in liveborn children?

These chromosomes carry comparatively few genes, so the dosage imbalance, while serious, is more often survivable to birth than trisomy of larger, gene-rich chromosomes, which is typically lethal early in development.

What is mosaic trisomy?

Mosaic trisomy means only some of a person's cells carry the extra chromosome while others are normal, usually because the error happened after fertilisation during mitosis; the proportion and distribution of trisomic cells can influence the clinical picture.