Classification of hereditary diseases
Medical genetics distinguishes several main groups of hereditary pathology depending on the level of damage to the genetic apparatus and inheritance mechanisms:
- Gene diseases (monogenic, Mendelian) are caused by damage to a single gene.
- Chromosomal diseases — associated with changes in the structure or number of chromosomes.
- Multifactorial diseases (polygenic) are diseases with a genetic predisposition that require exposure to environmental factors.
- Mitochondrial diseases are the result of mutations in mitochondrial DNA.
- Maternal-fetal incompatibility diseases — for example, the development of Rh conflict.
Gene diseases: inheritance types and pathogenesis
The pathogenetic basis of gene diseases consists of the following cascade: mutation in a gene → synthesis of a defective protein or enzyme → metabolic disruption. Such metabolic blocks are often called "enzymopathies".
Main types of inheritance and examples of pathologies:
- Autosomal dominant: polydactyly, Huntington's chorea, Marfan syndrome.
- Autosomal recessive: albinism, cystic fibrosis, phenylketonuria.
- X-linked (recessive): color blindness, hemophilia.
Chromosomal aberrations
This group of diseases and syndromes arises from changes in chromosome number. The main mechanism is impaired normal chromosome segregation during sex cell maturation (gametogenesis).
- Autosomal anomalies (trisomies): Patau syndrome (trisomy 13), Edwards syndrome (trisomy 18), Down syndrome (trisomy 21).
- Sex chromosome anomalies: Turner syndrome (karyotype 45, X0), Klinefelter syndrome (karyotype 47, XXY).
Hereditary lipid metabolism disorders
A striking example of genetic pathology is primary hyperlipidemias and hypercholesterolemias (with a prevalence ranging from 1 to 2,000 per 1 million people). According to the Goldstein–Brown theory, the pathogenetic basis lies in mutations of the genes encoding the synthesis and function of LDL receptors.
Clinically, these conditions manifest as pronounced early atherosclerosis, predominantly affecting the coronary arteries.
| Form of pathology | Main pathogenesis |
|---|---|
| Familial hypercholesterolemia | Deficiency of cellular LDL receptors |
| Familial hypo-α-lipoproteinemia | Defect of apolipoproteins A-I/A-II → decrease in HDL → blockade of reverse cholesterol transport |
| Cholesteryl ester storage disease | Defect of lysosomal acid lipase → impaired cholesterol catabolism |
Principles of diagnosis, prevention, and treatment
To reduce the risk of having children with genetic defects, medical genetic counseling, prenatal diagnosis, and strict avoidance of mutagen exposure are used.
Therapy for hereditary diseases involves three approaches:
- Symptomatic: elimination of specific manifestations of the disease.
- Pathogenetic: blocking the mechanisms of development (e.g., strict dietary therapy for phenylketonuria, replacement therapy with insulin or blood clotting factors, removal of accumulated toxins).
- Etiological: the most promising approach, including genetic engineering and gene therapy methods to correct the defect itself.
To remember the chromosome numbers in autosomal trisomies, use the mnemonic PED in ascending order: Patau (13) — Edwards (18) — Down (21).
Class and exam questions
What are multifactorial diseases?
These are diseases with a polygenic basis (involving multiple genes) whose phenotypic manifestation requires exposure to specific environmental triggering factors.
What is the molecular-level pathogenesis of monogenic diseases?
A mutation in a single gene leads to the synthesis of a structurally or functionally defective protein (most often an enzyme) by the organism, causing a severe metabolic disruption.
Is it possible to target the cause of hereditary pathology?
Yes, etiological treatment of hereditary diseases is possible using gene therapy methods, which allow for the correction of genetic defects.
What else to study on this topic
- Genocopies and phenocopies in medical genetics.
- Anti-mutational defense systems of the organism.
- Constitution and constitutional anomalies as a risk factor for diseases.
- Pathogenic effects of ionizing radiation (stochastic effects, radioprotection).
- Pathogenesis of exogenous and endogenous intoxications (including substance abuse and alcoholism).
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