Monosomy and Turner Syndrome

Monosomy is the loss of a single chromosome from an otherwise diploid set, leaving only one copy where there are normally two and a chromosome count of 45. Full autosomal monosomy is almost always lethal in early development; the principal monosomy compatible with live birth is monosomy of the X chromosome (45,X), which causes Turner syndrome.

Definition

A monosomy is an aneuploid state in which one specific chromosome is present in a single copy rather than two, so that the affected cell is missing one chromosome (45 in a diploid background); Turner syndrome is the clinical condition arising from complete or partial absence of one X chromosome in a phenotypic female.

Scope

The topic covers the concept of a missing chromosome, the meiotic and post-zygotic errors that produce it, and why monosomy is far less tolerated than the corresponding trisomy. Its central clinical example is Turner syndrome, including the full 45,X karyotype, mosaic forms, and structural X abnormalities. The entry is a reference description of these entities and their basis, not individualised clinical guidance.

Core questions

• Why is autosomal monosomy almost universally lethal while the corresponding trisomy may survive?
• Why is monosomy X uniquely compatible with live birth among complete monosomies?
• How do full 45,X, mosaic, and structural-X karyotypes relate to the Turner phenotype?
• What error in gamete formation leaves a conceptus with only one sex chromosome?

Key concepts

• Monosomy (45 chromosomes)
• Autosomal monosomy lethality
• Monosomy X (45,X)
• Turner syndrome
• Mosaicism (45,X/46,XX)
• Structural X abnormalities (isochromosome, ring X)
• X-chromosome inactivation and dosage
• Nondisjunction and anaphase lag

Mechanisms

Monosomy arises when a gamete lacks a chromosome, usually because of nondisjunction in meiosis, or when a chromosome is lost after fertilisation through anaphase lag, in which a chromosome fails to attach properly and is left out of a daughter nucleus. The loss of an entire chromosome removes a large block of genes, and for autosomes this deficit is generally incompatible with development. The X chromosome is exceptional: because cells normally inactivate all but one X, a single active X is tolerable, although certain genes that escape inactivation are present at reduced dosage, which is thought to contribute to the Turner phenotype. Many individuals with Turner syndrome are mosaic or carry a structurally abnormal second X rather than a pure 45,X karyotype.

Clinical relevance

Turner syndrome is the clinically important monosomy in liveborns and is managed across the lifespan by multidisciplinary teams, the subject of dedicated international clinical practice guidelines. This entry summarises the genetic basis and recognised features as reference material; it does not provide diagnostic thresholds or treatment recommendations for any individual.

Epidemiology

Most 45,X conceptions are lost early in pregnancy, making monosomy X a frequent finding in spontaneous abortion, while only a minority survive to birth. Turner syndrome affects phenotypic females and, unlike trisomy, does not show a strong maternal-age effect; a substantial proportion of liveborn cases are mosaic or involve a structurally abnormal X rather than complete monosomy.

History

The clinical features later called Turner syndrome were described in 1938, and in 1959 the condition was shown to result from absence of one sex chromosome (a 45,X karyotype), in the same year that trisomy 21 was identified — together establishing that both gain and loss of a chromosome could cause human disease. Later work characterised the spectrum of mosaic and structural-X forms and, more recently, consolidated lifespan care in international guidelines.

Key figures

• Henry Turner
• Charles Ford
• Claus Gravholt

Seminal works

• gravholt-2017
• hassold-hunt-2001

Frequently asked questions

Why can a person survive with monosomy X but not with monosomy of an autosome?

Cells normally silence all but one X chromosome, so having a single active X is close to the usual functional state, whereas losing an entire autosome removes one of only two copies of many essential genes and is generally lethal in early development.

Does everyone with Turner syndrome have a 45,X karyotype?

No. Many individuals are mosaic, carrying a mixture of 45,X and normal cells, or have a structurally altered second X chromosome; the exact karyotype varies and can influence the clinical features.