How hereditary diseases are inherited

Every hereditary disease is inherited either monogenetically or polygenetically: this means that there is one or more gene locus that must be altered in order to cause a disease. Furthermore, genetic traits can always be inherited dominantly or recessively: Recessive means that there must be a predisposition for this particular hereditary disease in both the paternal and maternal genes. In the case of dominant inheritance, a change (i.e. of one parent) is sufficient to trigger the disease.

This means that in the case of dominant inherited diseases, the people who are the carriers of the disease will also become ill – whereas in the case of recessive inheritance, it is usually not even known that a corresponding genetic disposition is present. There are also diseases that are inherited via the sex chromosomes, such as hemophilia or red-green blindness. These are usually located on the X chromosome, since the Y chromosome is very small and generally has little genetic information to store.

This is why they are also called X-linked diseases. These usually affect significantly more men than women, since in women the possibly incorrect information on the X chromosome can be compensated by the second. How exactly a genetic disease is inherited can usually be easily researched.

Tests before birth

In principle, the child’s genetic material can be examined in the womb for all hereditary diseases whose causative gene locations are known. However, genetic analyses are time-consuming, so usually only the suspected gene locus is analyzed – for this in turn, the well-founded suspicion of a genetic disease must be present. For such an examination, genetic material can then be taken from the amniotic fluid or placenta and used for the analysis.However, it should always be remembered that any invasive diagnostic procedure also involves a risk to the life of the unborn child.

Such punctures must therefore be weighed individually in each case. In addition, there are measurements that can provide indications of a genetic disease, such as nuchal translucency measurement as a sign of trisomy 21. Such methods are not dangerous for the unborn child, but cannot provide absolute certainty about the presence of a genetic disease.

Therefore, their use must also be well thought out. The cause of trisomy 21 is chromosome 21, which is present not twice but three times in affected individuals. This variant of the DNA is formed during the distribution of chromosomes in the parental germ cells, i.e. the sperm or the eggs.

It is therefore a “distribution error” and not a change in the actual genetic material. This explains why trisomy 21 can occur spontaneously in any family and why the probability of having a child with Down syndrome is the same in all families. Strictly speaking, trisomy 21 – like other trisomies – should not be considered a hereditary disease in the true sense of the word.

Nevertheless, trisomy 21 is the most common disease caused by DNA in newborns. Characteristics of the altered chromosome set in Down syndrome can already be seen in the unborn child in the womb: Growth retardation and growth defects can lead, among other things, to a skull that is too small, short bones of the thigh and upper arm, and heart defects. A large amount of amniotic fluid can also be an indication of trisomy 21, since affected unborn children drink or swallow comparatively little amniotic fluid.

However, all these characteristics are not definitive signs of Down syndrome! In addition to the signs of growth retardation mentioned above, children with Down syndrome often show delayed development in areas such as speech and motor skills. Remarkable social skills can often be observed in people affected by Down syndrome, whereas intelligence often remains below average.

However, affected people differ greatly in these characteristics, and it is not uncommon for a person to graduate from school after receiving good support. As life progresses, people with trisomy 21 have an increased risk of being diagnosed with certain diseases. These include Alzheimer’s disease, epilepsy and cancer, especially leukemia.

Nevertheless, the life expectancy of people with Down’s syndrome continues to rise: In the meantime, affected people often reach the age of 60 or 70. Alpha-1-antitrypsin deficiency can have different forms and manifestations, depending on the exact genetic characteristics of the person affected. This means that not every Alpha-1-Antitrypsin Deficiency leads to symptoms.

The following section will therefore only deal with the clinically conspicuous type (PiZZ) of this genetic disorder. The enzyme defect present in this disease causes the degradation and conversion of building blocks in the organ tissue of affected individuals. In addition, the defective proteins are filtered from the blood by the liver and accumulate there.

As a result, liver inflammation (hepatitis), liver cirrhosis or liver cancer can occur. In the lungs, the lack of stable tissue makes the airways unstable and they collapse faster: The clinical picture of COPD (chronic obstructive pulmonary disease) develops. Often this clinical picture is the first symptom of an Alpha-1-Antitrypsin Deficiency.

Every person with COPD at a younger age should therefore be checked for Alpha-1-Antitrypsin Deficiency. If the disease persists for a longer period of time, the lungs may become over-inflated, as the air cannot be exhaled properly through the unstable airways and accumulates in the lungs. As a therapy, in addition to consistent avoidance of cigarette smoking and regular vaccinations to prevent respiratory diseases, medicinal measures should also be taken: The missing alpha-1-antitrypsin can be administered intravenously to alleviate the symptoms as far as possible and halt the progression of the disease.

You can find more information on our Alpha-1-Antitrypsin DeficiencyThe group of hemophiliacs is colloquially known as “hemophilia“, as this term already describes the main symptom of this hereditary disease quite accurately: The affected persons bleed longer and, depending on the severity of the disease, more often than those who are not affected. Bleeding is normally stopped by the so-called coagulation cascade, a signaling pathway that is intrinsic to the body and prevents major blood loss.In this coagulation system, 13 factors play a role, which activate each other one after the other. This can be imagined as a series of dominoes: If you hit a stone (clotting factor), it activates the next one, and so on.

At the end of this signal path or the dominoes is the coagulation of the blood. In hemophilia, depending on the specific subtype of the disease, a certain factor is now missing: the chain reaction stops here. A therapy of the disease can be carried out by determining the missing factor and supplying it from outside.

Affected persons must therefore regularly inject themselves with a preparation containing this coagulation factor so that the rest of the chain reaction can also take place. In the genetically determined disease cystic fibrosis, there is a faulty production of ion channels, more precisely of chloride channels. As a result, the composition of the body secretions (such as sweat, respiratory and pancreatic secretions) of the affected person is altered: Since the lack of chloride means that less water is drawn into the excretory duct of the respective gland, the secretion is relatively viscous.

As a result, symptoms usually develop in the digestive tract, since the secretion with the digestive enzymes cannot flow easily from the pancreas into the intestine, thus damaging the pancreas itself. In addition, digestive disorders such as fatty stools, diarrhea and the resulting low body weight are often observed. The second major group of symptoms usually develops in the lungs: Since the mucus that occurs naturally in the lungs is more viscous than in healthy people, it is harder for the cilia to transport it away.

This can result in chronic coughing and obstruction of the bronchi (bronchiectasis). The larger amount of lung secretion also provides a good environment for the growth of bacteria, resulting in frequent respiratory infections and pneumonia. Cystic fibrosis is treated symptomatically with, among other things, mucolytics, digestive enzymes and antibiotics for infections.

A factor V Leiden mutation is a change in genetic information that can cause increased blood clotting. The reason for this is factor V in the body’s so-called coagulation cascade: this signaling pathway ensures that the wound is closed by the body’s own “adhesive proteins” (fibrin) when an injury occurs. There are 13 factors in this signaling pathway, which are designated by Roman numerals (i.e. “factor 5 suffering”!).

Factor V has a beneficial effect on the formation of a fibrin plug, but can also be inhibited by the so-called activated protein C (APC for short). This plays an important role in regulating this signaling pathway and preventing excessive blood clotting. The mutated factor V is present in the affected individuals, but does not respond to APC.

The body therefore lacks an important “safety device” at this point to prevent unprovoked blood clotting, which may even occlude vessels and thus cause circulatory disorders. Statistically speaking, people affected by a Factor V Leiden mutation are therefore more likely to suffer a thrombotic event (i.e. thrombosis or pulmonary embolism), even without having a history of typical risk factors. This is also known as “thrombophilia“, i.e. a tendency to clot.

In Gaucher’s disease, the change in the DNA information causes a defect in an enzyme of the fat metabolism, more precisely glucocerebrosidase: this helps to break down old cell building blocks. A defect can therefore lead to a reduction in function or even a loss of function. Accordingly, the symptoms already occur in childhood or young adulthood.

The symptoms of Gaucher’s disease are largely due to an enlargement of the liver and spleen, with the growth of which the body tries to compensate for the enzyme deficiency. This increases the breakdown of all blood components, which can be recognized in the blood count and used together with the enlargement of the liver and spleen as a diagnostic indication. Therapeutically, the missing enzyme glucocerebrosidase can be administered as a drug.

The prognosis and course of Gaucher’s disease is largely dependent on the severity of the enzyme’s loss of function. Osler’s disease is a hereditary disease characterized by severe vascular dilatation. In principle, this dilatation of the vessels can occur anywhere, i.e. both on the skin and on internal organs.

The walls of the dilated vessels are relatively thin and easily tear. As a result, bleeding quickly occurs at the affected areas.Vasodilatation of the face and nasal mucous membranes is particularly common, and the affected individuals therefore usually complain of frequent nosebleeds and small spot-like bleedings on the face. If Osler’s disease is suspected, appropriate diagnostics should be carried out, since vasodilatation can also occur in vital or well supplied organs such as the lungs, brain or liver, where bleeding from a torn vessel is dangerous.

Neurofibromatosis type 1 -or Recklinghausen’s Disease – is a genetic disease in which the affected individuals often develop tumors on the cells of the nerve sheath. The resulting tumors can be either benign or malignant and can occur at a young age. Typical tumors, however, are the benign neurofibromas: These consist of cells that coat and insulate the nerve like an electric cable, as well as the surrounding connective tissue.

They are benign, i.e. non-scattering and slow-growing tumors. Nevertheless, surgery to remove neurofibromas can be difficult under certain circumstances, as they are often firmly attached to the nerve and the corresponding nerve must then be removed. Nevertheless, this is the only treatment option for symptomatic neurofibroma, since a causal therapy for this hereditary disease is not possible.

You can find more information on this topic on our page Neurofibromatosis Type 1The term muscular dystrophy describes a group of hereditary diseases in which certain muscle components cannot be assembled or cannot be assembled correctly by the body cell. As a consequence, the affected persons usually develop muscle weakness and loss of muscle mass already in childhood and adolescence, movement restrictions up to physical disability can be the consequence. If the presence of muscular dystrophy is suspected, blood values should first be determined.

If the values match the suspected diagnosis, a muscle biopsy can still be performed: In this procedure, a small tissue sample is taken from the muscle, which is then examined microscopically for cellular defects. A genetic examination is also possible for the diagnosis, since for the various forms of muscular dystrophy, the corresponding gene locations are usually known, which would have to be altered. A causal therapy for muscular dystrophies is not known.