Autosomal Inheritance

Autosomal Dominant Inheritance

In autosomal dominant inheritance, the mutant gene is aggressive and overrides the normal allele. The disorder is transmitted from generation to generation, which appears as a vertical transmission pattern on a pedigree analysis.

• Parents: Typically, one of the parents is affected. The only exception is when the pathology is the result of a de novo (new) mutation.
• Offspring: The probability of an affected parent having an affected child is exactly 50%. This risk remains constant regardless of the child's sex or the number of children in the family.
• Unaffected Relatives: Unaffected family members have healthy offspring because they do not carry the mutant gene.
• Key Features: The frequency of the pathology is equal in males and females. The severity and number of clinical manifestations (expressivity) directly depend on environmental factors.

Examples of Autosomal Dominant Pathologies

Typical disorders with this transmission mechanism include:

• Marfan syndrome;
• Huntington disease;
• Neurofibromatosis;
• Familial hypercholesterolemia;
• Hemoglobin M disease;
• Familial adenomatous polyposis;
• Polydactyly.

Autosomal Recessive Inheritance

For an autosomal recessive pathology to manifest, an individual must inherit a mutant gene from both parents simultaneously. In a pedigree, these disorders are distributed horizontally: they frequently appear among brothers and sisters (sibs).

• Parents: The patient's parents are usually unaffected carriers. The disorder may unexpectedly appear in other relatives, such as first or second cousins.
• Clinical Presentation: Symptoms typically manifest in childhood. In the homozygous state, manifestations are more uniform due to high penetrance.
• Sex Distribution: Similar to the dominant type, the frequency of the pathology is equal in males and females.
• Half-Sibs: The disorder is typically absent in half-sibs. Paternal half-sibs (sharing the same father but different mothers) and maternal half-sibs (sharing the same mother but different fathers) remain unaffected.

Risk Factor: Consanguineous Marriages

The emergence of autosomal recessive disorders becomes significantly more likely in consanguineous marriages. The mechanism is straightforward: such unions drastically increase the probability that both spouses are heterozygous for the same pathogenic allele inherited from a common ancestor. On pedigree charts, a consanguineous union is denoted by a double line.

Examples of Autosomal Recessive Pathologies

Disorders with an autosomal recessive transmission mechanism include:

• Cystic fibrosis;
• Phenylketonuria;
• Galactosemia and glycogen storage diseases;
• Oculocutaneous albinism;
• Congenital adrenal hyperplasia (CAH);
• Chediak-Higashi syndrome;
• Hyperlipoproteinemias.

Pedigree Analysis and Symbols

To graphically represent inheritance patterns (e.g., in Marfan syndrome or cystic fibrosis), standard pedigree symbols are used:

• Square — male;
• Circle — female;
• Filled circle or square — affected family member;
• Filled symbol with a diagonal slash — deceased affected individual;
• Arrow — points to the proband (the index case through whom the family history is initiated).