Clinical AreaEndocrinology

Here you will find the disease-related gene panels available for the clinical area specified above.

If you cannot find the disease you are looking for, please use a known synonym in the search (also in English).

Genetic diagnostics are used to clarify the hereditary causes of endocrinological diseases. The aim here is to detect deviations from the reference genome ("wild type") and then, if necessary, to distinguish between neutral variants and pathogenic mutations that are important for the physiological development and undisturbed functioning of the hormone metabolism. The inheritance patterns of heritable endocrinological diseases represent the basis of genetic counselling for patients, persons at risk and affected families. In the last 30 years, several hundred genes have been characterized which may cause such diseases or contribute to the development of endocrinological diseases. Current research results have a direct impact on the diagnostic procedure in the laboratory and in genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable, hereditary diseases. On the other hand, different mutations in one and the same SDHB gene lead to clinically apparently separated disease entities (pheochromocytoma vs. gastrointestinal stromal tumors).

Formal genetically and etiologically the following groups of neurogenetic diseases can be distinguished:

• monogenic diseases (autosomal or X-chromosomal inheritance)
• mitochondrial diseases (maternal or autosomal inheritance)
• multifactorial diseases (interaction of several to many genes plus environmental factors)

Congenital malformations of the hormone systems often appear sporadically - is there a genetic (co-)cause? Numerous inherited endocrinological diseases are demonstrably based on genetic changes and lead to disorders in proteins that build up the central nervous system and peripheral nerves. DNA diagnostics therefore often involves a step-by-step procedure in which the most frequent mutations are first tested before the very rare genetic causes are also identified in parallel approaches using extensive and cost-intensive panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using Sanger technology. The following are examples from some of the more common disease groups.

Disorders of sexual development and sex hormone synthesis etc. affect, among others, androgen insensitivity, premature ovarian failure and other complex syndromes. Hypothalamic and pituitary diseases, e.g. combined pituitary hormone deficiencies (septooptic dysplasia, agenesia of the corpus callosum) are based on HESX1 gene alterations. Kallmann syndrome (hypogonadotropic hypogonadism, anosmia, renal agenesia) is genetically very heterogeneous and can be caused by mutations in a dozen different genes (CHD7, FGF8, FGFR1, KAL1, PROK2, PROKR2 etc.).

Thyroid hormone synthesis, transport and hormone action include congenital hypothyroidism with mutations in several genes (NKX2-5, PAX8, THRA, TSHB, TSHR etc.) as well as complex syndromes involving several organ systems (e.g. Pendred Syndrome and others). Hereditary disorders of the parathyroid glands (hypoparathyroidism) as well as of the bones (including genetically determined forms of rickets) are also observed like very rare and complex syndromes.

Nowadays, adrenal cortex hormone synthesis failures and various types of glucocorticoid deficiency as well as peroxisome defects and the adrenogenital syndrome can be directly diagnosed by genetic methods. Failed or reduced beta cell function of the pancreas as well as its development as an organ can often only be differentiated beyond doubt by molecular genetic methods, e.g. in special forms of diabetes ("maturity-onset diabetes of the young", MODY1-14). Genetically caused disorders of the water / salt balance, e.g. diabetes insipidus, Gitelman and Bartter syndrome etc. can also be differentially diagnosed by modern methods of molecular genetics.

Tumour syndromes with endocrine manifestation either originate from hormone-producing cells or organs (multiple endocrine neoplasias) or occur in other tissues, such as Peutz-Jeghers syndrome.

Monogenic defects of the fat metabolism are comparatively very rare, mostly obesity is known to occur on a multifactorial basis, i.e. primarily polygenic and above all dependent on environmental factors such as diabetes mellitus type 1 and 2. Nevertheless, predisposition and susceptibility factors can also be determined by molecular genetics like known HLA-DR and -DQ antigen genes, promotor polymorphisms in the insulin gene as well as particular phenotypes resulting from variations in specific genes (NEUROD, CTLA4, PPARγ, INS, SUR1, PDX1 (IPF1), IRS-1 etc.).