The genetic information that dictates human development and function is organized into structures called chromosomes. A typical human cell has 46 chromosomes, arranged in 23 pairs, with one set inherited from each parent. This balanced number is known as euploidy. Errors in cell division can lead to an abnormal number of chromosomes, a genetic variation called aneuploidy. Aneuploidy involves the gain or loss of an entire chromosome.
Defining Monosomy
Monosomy is a specific form of aneuploidy characterized by the absence of one chromosome from a pair, resulting in a total of 45 chromosomes per cell instead of the usual 46. Genetically, this condition is formally noted as 2n-1, meaning the diploid number of chromosomes (2n) is missing one member.
This state contrasts with euploidy (the normal complement of 46 chromosomes) and trisomy (the presence of an extra chromosome, 2n+1). For example, a missing X chromosome results in a karyotype written as 45, X, indicating 45 total chromosomes with only a single X sex chromosome. Monosomy represents a reduction in genetic material, which profoundly disrupts the balance of gene expression required for healthy development.
How Monosomy Occurs
The underlying biological process that causes monosomy is called nondisjunction, meaning the failure of chromosomes to separate correctly. This event occurs during meiosis, the specialized cell division that produces sperm and egg cells (gametes). Nondisjunction can occur in two distinct stages of meiosis.
In meiosis I, a homologous pair of chromosomes may fail to separate, leading to one daughter cell receiving both copies and the other receiving none. If the error occurs in meiosis II, the sister chromatids of a chromosome fail to separate. In either scenario, the result is a gamete that is missing a chromosome, designated as n-1.
When this gamete combines with a normal gamete during fertilization, the resulting embryo’s cells will be monosomic. These errors occur spontaneously and are the primary source of whole-chromosome monosomy.
Autosomal vs. Sex Chromosome Monosomy
Human chromosomes are divided into 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes (XX or XY). Monosomy can affect either type, but the consequences differ significantly due to gene dosage, which is the number of copies of a gene present. The body requires two copies of most genes for normal function.
The loss of an entire autosome (chromosome 1 to 22) creates a severe imbalance in gene dosage that is almost universally incompatible with life. The resulting embryo typically fails to develop and is lost through spontaneous miscarriage early in pregnancy. This occurs because autosomes carry thousands of genes essential for cellular and organ development.
In contrast, monosomy involving a sex chromosome, specifically the loss of an X chromosome (Monosomy X), is often viable. This tolerance is due to X-inactivation, a unique biological process that occurs naturally in females. In females with two X chromosomes, one X chromosome is randomly silenced in each cell during early development. Since the body functions with only one active X chromosome, the loss of a second X chromosome is much better tolerated than the loss of any autosome.
Specific Conditions Resulting from Monosomy
The sole condition resulting from a complete, full-chromosome monosomy that is compatible with human life is Turner Syndrome (TS), or Monosomy X. This condition affects females and is characterized by the karyotype 45, X, meaning one of the two X chromosomes is missing. Although viable, the condition is associated with a specific set of physical and developmental features.
Common clinical manifestations of Turner Syndrome include short stature and the failure of the ovaries to develop correctly, leading to ovarian insufficiency and infertility. Other physical characteristics may involve a webbed neck, a low hairline, and skeletal abnormalities. Heart defects, particularly involving the aorta, and kidney malformations are frequently observed health considerations.
Partial Monosomies
While complete autosomal monosomies are lethal, some extremely rare conditions involve the loss of only a small segment of a chromosome, known as partial monosomies. These partial deletions, such as Cri du chat syndrome (a deletion on chromosome 5), result in different consequences than the loss of an entire chromosome. The vast majority of human monosomies result in non-viability, reinforcing the exceptional nature of Turner Syndrome.