Turner syndrome

Genetic mechanisms and pathogenesis

Turner syndrome is based on a genomic mutation, specifically an abnormality in chromosome number — aneuploidy. The mechanism of the pathology is closely related to errors during gametogenesis. Due to impaired normal meiosis, nondisjunction of homologous sex chromosomes occurs, leading to the formation of unbalanced gametes.

Turner syndrome belongs to the broad group of chromosomal diseases. These congenital hereditary disorders are traditionally characterized by the presence of multiple congenital malformations (MCM) in the patient. At the same time, the 45, X0 variant is unique: it is the only monosomy in the human population that allows for the birth of a live child. Most other variants of aneuploidies, as well as polyploidies (triploidy $3n$, tetraploidy $4n$), are lethal mutations and are found exclusively in aborted embryonic tissues.

Clinical presentation

Despite the absence of one sex X chromosome, patients with Turner syndrome have a strictly female phenotype. Nevertheless, the genetic defect leads to severe abnormalities in organism development and multiple congenital malformations.

Main clinical manifestations of the syndrome:

• Short stature (pronounced physical growth retardation).
• Delayed puberty.
• Underdevelopment of internal genital organs.

These symptoms are caused by a lack of genetic material necessary for the adequate functioning of the endocrine and reproductive systems.

Role in pregnancy pathology and spontaneous abortions

Chromosomal and gene mutations are the leading cause of embryonic death in early gestation. Monosomy 45, X0 accounts for a colossal share in the structure of spontaneous abortions — 20–30% of all chromosomal abnormalities in abortuses (for comparison: autosomal trisomies make up 45–55%, triploidy — 15–20%, and tetraploidy — 5%).

The most critical period is the first weeks of development:

1. At 6–7 weeks, the abnormal karyotype is registered in 60–75% of fetal death cases.
2. At 12–17 weeks, the detection rate drops to 20–25%.
3. By 17–28 weeks, chromosomal aberrations are found in only 2–7% of cases.

When fetal development halts within the first 2–3 weeks after fertilization, clinical bleeding often completely coincides with a normal menstruation. In such cases, the fact of pregnancy is established only through hormonal screening. It is precisely because of undiagnosed early losses that the true incidence of spontaneous abortions reaches 30–40% (while only 10–20% are clinically diagnosed).

Place in the mutation classification

Pathology of meiosis leads to the formation of defective germ cells, which becomes the fundamental cause not only of congenital syndromes, but also of infertility and recurrent pregnancy loss.

Such diseases can be based on two types of mutations:

• Structural (chromosomal) — changes in the structure of the chromosome itself. These include deletions (loss of a segment), duplications (doubling), inversions (180° rotation), and translocations (transfer of a fragment).
• Quantitative (genomic) — changes in the number of chromosomes. Turner syndrome belongs to this exact group. In addition to the viable monosomy 45, X0, this group includes viable sex chromosome polysomies (karyotypes XXX, XXXY, XXXYYY) and trisomies (Down, Patau, Edwards syndromes).

Class and exam questions

What else to study on this topic

• Autosomal trisomies (Down, Patau, Edwards syndromes) and their genetic mechanisms.
• Infectious and extragenital factors of pregnancy loss (SLE, diabetes, CMV, rubella).
• Sex chromosome polysomies (XXX, XXXY, XXXYYY) and their clinical significance.
• Morphological evaluation of post-abortion material: chorionic villi and decidual tissue.
• Structural chromosomal mutations: mechanisms of formation of deletions, duplications, inversions, and translocations.

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