Pflegefachexperte CF Thomas Kurowski führt einen Lungenfunktionstest bei einer CF-Patientin durch.

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When genetic material makes you ill

Hereditary diseases are caused by mutations in the genetic material and can be passed on to offspring without the parents themselves having the disease. The most common hereditary disease in Europe is the metabolic disorder cystic fibrosis. Around 1,000 people in Switzerland are affected.

Hereditary diseases can be caused by one or more mutations in the genetic material. But they don’t have to. It is not uncommon for the hereditary disease not to appear at all in carriers of a genetic mutation or their offspring. The reason for this is different probabilities of inheritance, recurrence and illness. Depending on the constellation, the pathogenic “inheritance” can remain hidden for several generations. In addition, there are mutations that are linked to the sex chromosome and therefore only occur in men or women.

Congenital genetic defects can lead to a loss of function, manifest themselves in dysregulated tissue growth, disrupt certain metabolic reactions or cause the death of certain cell types. As a rule, hereditary diseases cannot be cured. For certain disorders, however, the course of the disease can be slowed down by medication and a wide range of therapies.

Genetic consultation provides clarity

If you have questions about possible hereditary diseases in your family or if couples need to rule out the possibility of a hereditary disease before planning a family, a visit to the genetic consultation at the University Hospital Zurich will provide clarity. Genetic tests are used to check the chromosomes for numerical and structural changes. In the case of a genetic disease or carrier, the course of the disease, any preventive measures or special treatment strategies as well as the inheritance pattern and the risk of recurrence are explained during the consultation.

Various research projects supported by the USZ Foundation also focus on hereditary diseases. In the case of prion disease, a progressive, degenerative and previously fatal disease of the brain, researchers are looking for the genes responsible in order to create a basis for the development of drugs. Another research team is investigating genetic eye diseases. This is because the more precisely the mutation is known, the more clearly the effects on the eyes can be localized and treated in a more targeted manner in childhood.

Well-known and widespread

One of the best known hereditary diseases is color blindness (achromasia). Those affected do not perceive colors at all or only to a limited extent (di-/monochrasia). That is why they are excluded from certain professions – pilot, train driver, car painter, printing, electrical engineering. However, this illness has little impact on coping with everyday life. Around eight percent of all men have a congenital color vision disorder. For women, the figure is only 0.4 percent.

Hemophilia is an inherited and incurable disorder of blood clotting. Thanks to modern therapies, however, people with hemophilia can lead a largely normal life. For every 10,000 men, two develop hemophilia. Women are practically not affected.

Short stature (achondroplasia) is a well-known but rare hereditary disease. The length growth of the long bones is impaired in those affected. The humerus and femur are shortened in this genetic growth disorder. However, the bones are of normal thickness and the torso is almost normal in length. There is one case of achondroplasia per 20,000 births.

Far more frequently, with one case per 700 births, a child is born with Down’s syndrome (trisomy 21). This is not actually a disease, but a chromosomal anomaly. Chromosome 21 is not present twice, but three times. Affected people therefore have 47 chromosomes instead of 46. Trisomy 21 is associated with varying degrees of physical malformations and mental limitations. Depending on the individual case and individual support, however, these people can lead a largely normal life. Around 120 children with Down’s syndrome are born in Switzerland every year.

The most widespread metabolic disease in Europe is cystic fibrosis (CF), also known as cystic fibrosis. Due to a defective gene, the mucus-producing cells do not function properly in those affected. Viscous mucus puts a strain on the organs and can lead to coughing, bacterial colonization and inflammation in the lungs. The lungs become increasingly damaged and the respiratory volume steadily decreases. Because the body cannot absorb various nutrients (especially fats and fat-soluble vitamins), digestion is also impaired, particularly in the pancreas, liver and gastrointestinal tract. The consequences include abdominal pain, diarrhea and reduced weight gain.

Around 1,000 CF patients live in Switzerland. An estimated 320,000 people in Switzerland are carriers of the defective genetic material. Around four percent of all people worldwide have a genetic defect that enables them to inherit cystic fibrosis.

Every newborn is tested

Since 2011, all babies in Switzerland have been screened for cystic fibrosis immediately after birth as part of a newborn screening program to ensure that those affected receive the best possible care as early as possible. A drop of blood is taken from the baby by pricking the heel. If the level of immunoreactive trypsin is elevated, the blood is examined for the most common gene mutations. If cystic fibrosis is suspected, the so-called sweat test is used, as the functional defect can be seen in the composition of the sweat. However, the disease can remain undetected for a long time in people born before 2011.

CF center at the USZ for 140 patients

Cystic fibrosis is chronic and progressive. It cannot be cured, but can be treated with therapy and medication. 24 CF centers/outpatient clinics throughout Switzerland care for patients. In Zurich, the children’s hospital treats those affected until they reach the age of majority. The CF Center of the Clinic for Pneumology at the University Hospital Zurich will then take over. “We are currently looking after around 140 patients,” says Thomas Kurowski, CF nursing expert and coordinator at the CF Center at the USZ. “Our oldest patient is 67 years old.” In Switzerland, around 50 percent of CF patients are now adults. Each CF center offers a wide range of medical care, nutritional counseling, social services, psychological counseling, physiotherapy and, with the coordinator, another important point of contact.

Game changer Trikafta

While the life expectancy of CF patients in the 1980s was just under 20 years, it is currently almost 50 years and continues to rise year on year. The drug Trikafta is likely to have played a major role in this development.

In 1989, researchers identified the genetic defect that underlies cystic fibrosis. Another 15 years passed before the first drug was launched on the market that works precisely where the disease develops: on the CFTR channel. With Trikafta, the fourth generation of CFTR modulators is now in use.

On January 1, 2021, the Swiss Medicines Agency Swissmedic granted Trikafta approval for CF patients aged twelve and over. The use of the drug is a complete success. “Around 80 percent of CF patients respond to Trikafta. For them, taking it is associated with a marked improvement in their quality of life,” confirms Macé Schuurmans, Head of the CF Center at the USZ. “Trikafta is a real game changer. It can improve lung function by 20 percent or more.” However, the drug comes at a price of around 15,000 francs per month. Macé Schuurmans emphasizes: “If we manage to enable our patients to avoid a lung transplant with this drug and remain employed, it will have been worth it.”

Thanks to Trikafta, patients are healthier and have fewer symptoms. They experience a far-reaching normalization of life, combined with a greater workload. This not only eliminates physiotherapy and disability pension costs, but also improves the quality of life of those affected and enables them to resume their role in society.

Meanwhile, drug developers are continuing their work at full speed. Other active ingredients should soon be ready for use. This is because 20 percent of CF sufferers with other genetic characteristics are still waiting for effective help to mitigate the consequences of their disease-causing inheritance.

Grafik autosomal-dominante Erbgang

A distinction is made between autosomal recessive, dominant, gonosomal and mitochondrial inheritance. In another form, multifactorial diseases, the disease only develops in the course of life. Gonosomes are the two sex chromosomes X and Y. All other chromosomes are called autosomes.

  • Autosomal dominant inheritance independent of sex. Occurs in every generation. An altered allele, one of two corresponding genes of homologous chromosomes, leads to the expression of the trait. Examples: Achondroplasia (short stature), retinoblastoma (retinal tumor), polydactyly (multi-fingeredness).
  • Autosomal recessive inheritance independent of sex. Can skip generations. For the disease to break out, the gene mutation must occur on both chromosomes. In most cases, this is a loss-of-function mutation. Examples: Cystic fibrosis, cleft lip and palate, albinism.
  • Other inheritance patterns In gonosomal inheritance patterns, the changes affect the X and Y sex chromosomes. If the genetic material in the cell is intact, but there are errors in the DNA of the mitochondria, this is referred to as mitochondrial inheritance.

Genetic counseling consultation

Genetic counseling can be useful if there is a high incidence of cancer in a family or if it occurs at a younger age – especially in the case of tumors of the breast, ovaries and intestines. Genetic counseling primarily serves to record and evaluate the facts from the family and personal medical history.

Information on genetic counseling

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