Genetic testing in endocrinology
Genetic disorders of the endocrine system include monogenic, polygenic, and multifactorial or complex disorders. Within the group of endocrine gland disorders, there are disorders of reproduction and sexual differentiation, growth and development disorders, metabolic disorders, and disorders of regulation of nutrient supply and homeostasis. Genetic tests enable diagnosis and personalized therapy, but also provide important information for other family members of the affected individual. Next-generation sequencing (NGS) can help identify the causes of endocrine diseases, especially when hormone tests give ambiguous results. Additionally, genetic tests can detect whether there is a hereditary component and enable planning of treatment for various endocrine disorders, including obesity, diabetes, thyroid disease, and the risk of developing tumors of the endocrine glands (hypothalamus, pituitary, pineal, thyroid, parathyroid, pancreas, adrenal glands, ovaries, and testes).
Early diagnosis and personalized approach to treatment
Early diagnosis and personalized approach to treatment can significantly impact the prognosis of the disease. At the St. Catherine Special Hospital, we implement an integrative model of personalized medicine that allows genetic testing of a total of 563 genes associated with cardiovascular and endocrine diseases (My Genome cardiometabolic panel). As part of the testing, we offer patients tests to assess their risk of developing tumors, as well as nutrigenetic tests to approach each patient individually and optimize their nutrition for the prevention of cardiovascular, endocrine, and oncological diseases, which are now the leading causes of death in Croatia and the world, and which can mostly be prevented with a healthy lifestyle and proper nutrition.
The latest reports from the World Health Organization indicate epidemic proportions of obesity in the European population, and it has been found that obesity causes around 200,000 cases of cancer and 1.2 million deaths annually. Throughout Europe, 59% of adults are overweight or obese, as are 8% of children under five. Research shows that in some people, genes can cause up to 80% increased risk of being overweight. Although they vary, these scientific data give a rough idea of the important role of genetics in the development of overweight. Nutrigenetic testing can determine how specific gene variants in DNA can affect nutrients and supplements you ingest through food, and the results can help you adapt your nutrition plan to maintain normal body weight.
Genetic testing has many potential benefits for the patient and their wider family in making a diagnosis. Genetic testing is crucial in the diagnosis and early detection of inherited monogenic syndromes such as multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2). The advancement of DNA sequencing technology, specifically next-generation sequencing (NGS), has resulted in an intensive period of discovery of genetic diseases in the field of endocrinology and has provided a better understanding of the molecular-genetic basis of many endocrine disorders.
Monogenic endocrine disorders are most commonly caused by mutations in the coding sequence of DNA (genes) within germ cells (germline mutations). This group of disorders includes monogenic diabetes, Kallmann syndrome, familial hyperaldosteronism, multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), 21-hydroxylase deficiency, and other endocrine disorders. To successfully identify and diagnose these disorders, it is important to understand the mode of inheritance, the type and classification of genetic variants responsible for the disease, the penetrance of certain genes, and the degree of genetic heterogeneity.
Monogenic disorders can be inherited through one of six types of inheritance: autosomal dominant inheritance (e.g. MEN1 and MEN2 due to mutations in the MEN1 and RET genes, respectively), autosomal recessive inheritance (e.g. 21-hydroxylase deficiency due to mutations in the CYP21A2 gene), X-linked dominant inheritance (e.g. X-linked hypophosphatemia due to mutations in the PHEX gene), X-linked recessive inheritance (e.g. Kallmann syndrome due to mutations in the ANOS1 gene), Y-linked inheritance (e.g. azoospermia and oligospermia due to deletions in genes such as the USP9Y gene in the Y chromosome), and mitochondrial inheritance (e.g. hypogonadotropic hypogonadism and hypoparathyroidism associated with Kearns-Sayre syndrome due to deletions in mitochondrial (maternal) DNA (mtDNA)).
Genetic testing in endocrinology allows for timely detection of the disease in family members at risk, and the results of genetic tests can also affect the entire family, not just the individual undergoing testing. If your test result is positive and a pathogenic gene variant or variant of uncertain significance (VUS) is identified, there may also be a risk for the development of the disease in your family members. Family monitoring can identify other family members who are at risk for the same endocrine condition. Family members who are also positive for the pathogenic gene variant can work with their medical genetics specialist, endocrinology specialist, and nutritionist to develop a prevention plan and an early treatment plan for the disease.