The human body is composed of trillions of cells, each housing its genetic blueprint in chromosomes. These structures normally exist in pairs, carrying the organized sequence of DNA. Errors during cell division can lead to an abnormal number of chromosomes, a condition broadly categorized as aneuploidy. These numerical abnormalities can profoundly affect development and health, making them a central focus in medical genetics.
What Monosomy Means
Monosomy is a specific numerical chromosomal abnormality characterized by the absence of one chromosome from a homologous pair. Instead of the typical two copies, a person with monosomy has only one copy. This state is represented by the formula \(2n-1\), meaning the cell has 45 chromosomes instead of the usual 46 in humans.
Monosomy is distinct from trisomy (\(2n+1\)), which involves the presence of an extra, third copy of a chromosome. Both conditions are types of aneuploidy. The loss of an entire chromosome results in a significant reduction in the dosage of thousands of genes.
The impact of this missing genetic material is severe. Most complete monosomies involving autosomes (non-sex chromosomes) are incompatible with life. Embryos with a missing autosome typically result in spontaneous miscarriage or stillbirth. Consequently, viable monosomies are rare and generally involve the sex chromosomes or only a small portion of a chromosome.
Recognized Forms of Monosomy
The most common and clinically recognized form of complete monosomy resulting in a live birth is Monosomy X, also known as Turner Syndrome. This condition occurs in females who have only one X chromosome (45,X). Although the majority of 45,X conceptions are spontaneously aborted, survivors present with a distinct set of clinical features.
Turner Syndrome features include short stature and premature ovarian failure, often leading to absent puberty and infertility without hormone therapy. Prenatal findings may include a raised nuchal translucency or fluid accumulation known as hydrops fetalis. Individuals often exhibit a webbed neck, a low hairline, and an increased risk of specific health conditions, such as congenital heart defects (especially coarctation of the aorta) and renal anomalies.
Viability is also possible with partial monosomies, where only a segment of a chromosome is missing. Cri-du-chat syndrome is a well-known example, resulting from the deletion of a portion of the short arm of chromosome 5 (5p monosomy). The syndrome is named for the high-pitched, monochromatic cry of affected infants, which sounds similar to a meowing kitten due to laryngeal issues.
This partial deletion causes severe intellectual disability, developmental delay, and distinctive craniofacial features, such as microcephaly and a round face. The severity of the clinical presentation correlates with the size and location of the deleted segment. Approximately 90% of Cri-du-chat cases are sporadic, occurring randomly as a de novo deletion during the formation of reproductive cells.
How Monosomy Occurs
The primary cellular mechanism responsible for monosomy is nondisjunction, the failure of chromosomes to separate correctly during cell division. This error most often occurs during meiosis, the specialized process that creates sperm and egg cells (gametes). Nondisjunction can happen during Meiosis I, when homologous chromosomes fail to separate, or during Meiosis II, when sister chromatids fail to pull apart.
This failure to segregate results in gametes with an abnormal chromosome number. A gamete lacking a specific chromosome is termed nullisomic. When a nullisomic gamete is fertilized by a normal gamete, the resulting zygote has only one copy of that chromosome, leading to monosomy.
The risk of nondisjunction, and subsequent aneuploidy, increases with advanced maternal age. This increased risk is linked to the prolonged arrest of the egg cells in the female reproductive tract, making the meiotic process more prone to errors over time. Reduced activity of the spindle assembly checkpoint, which monitors chromosome separation, is thought to contribute to this age-related increase.
Diagnostic and Screening Methods
Detection of monosomy occurs prenatally through screening and diagnostic testing, or postnatally based on clinical presentation. Non-Invasive Prenatal Testing (NIPT) is a primary screening method that analyzes cell-free fetal DNA circulating in the mother’s blood. NIPT identifies pregnancies at increased risk for aneuploidies, including Monosomy X, with high sensitivity.
A high-risk NIPT result requires confirmation through an invasive diagnostic procedure. Procedures like amniocentesis or chorionic villus sampling (CVS) collect fetal cells directly for definitive analysis. The gold standard for confirming a numerical chromosomal abnormality is karyotyping, which involves staining and visually inspecting the chromosomes to determine their number and structure.
Fluorescence In Situ Hybridization (FISH) is frequently used alongside karyotyping for rapid analysis or to detect mosaicism. FISH utilizes fluorescent probes that bind to specific chromosomal regions, allowing for the quick counting of particular chromosomes or segments. This combination of methods allows geneticists to accurately diagnose monosomy, including cases of partial monosomy and mosaicism.