Acronym | Disorder | Gene / Chromosomal Region | OMIM | Genetic testing strategy* | Detection on different molecular levels (rates if available)** | Differential diagnosis | Mode of inheritance*** | |||
---|---|---|---|---|---|---|---|---|---|---|
SNVs | gene/exon targeted CNV analysis | CNVs | Epimut UPDs | |||||||
Genetic adrenal disorders* | ||||||||||
 ACC | Adrenocortical carcinoma | TP53 | #202300 | (1. sequencing of specific exons) 2. multigene panel | yes | yes |  |  | ADCC can be observed in Beckwith-Wiedemann syndrome (see below) and is a component tumor in Li-Fraumeni syndrome. | AD |
 APS1 | autoimmune polyendocrine syndrome type 1 | AIRE | #240300 | 1. single gene testing 2. multigene panel | yes | yes |  |  | Overlap with several disorders. | AR, AD |
 CNC | Carney complex | PRKAR1A | #160980 (type 1) | 1. single gene testing 2. CNV analyses 3. multigene panel | 60% | 10% |  |  | Broad clinical spectrum and overlap with several disorders. It includes Cushing syndrome. | AD |
 PPNAD | Primary pigmented nodular adrenocortical disease type 1 | PRKAR1A | #610489 | AD | ||||||
Primary pigmented nodular adrenocortical disease type 2 | PDE11A | #610475 | yes | Â | AD | |||||
Primary pigmented nodular adrenocortical disease type 3 | PDE8B | #614190 | yes | Â | AD | |||||
 21-OHD-CAH | 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia | CYP21A2 | #201910 | 1. single gene testing. CNV analysis | 70–80% | 20–30% |  |  | Major type of CAH. |  |
Calcium and Phosphate Homeostasis* | ||||||||||
 HRPT | Hyperparathyroidism | CDC73 | #145000 | Multigene panel | yes | yes |  |  |  | AD |
Neonatal Hyperparathyroidism | CASR | #239200 | yes | Â | Â | AD, AR | ||||
Familial Isolated Hypoparathyroidism | GCM2 | #146200 | yes | Â | Â | AD, AR | ||||
hypocalciuric hypercalcaemia | CASR GNA11 AP2S21 | #601198 #145981 #600740 | yes | Â | Â | AD | ||||
 PHP / iPPSD | Pseudohypoparathyroidism / Inactivated PTH/PTHrP Signalling Disorder | GNAS | #166350 #103580 #603233 #612462 #612463 | Methylation-specific test single gene testing CNV analyses | yes | yes |  | yes | Heterogeneous group of disorders caused by molecular changes of the imprinted GNAS locus. | AD |
 ADHR | Autosomal dominant hypophosphatemic rickets | FGF23 | #193100 | single gene testing | yes | yes |  |  |  | AD |
 XLHR | X-linked dominant hypophosaphatemic rickets | PHEX | #307800 | single gene testing | yes | yes |  |  |  | X-linked |
Genetic Pituitary Hormone Disorders* | ||||||||||
 CPHD | Combined Pituitary Hormone Deficiency | PROP1 | #262600 | (1. single gene testing) 2. multigene panel | yes | yes |  |  | The diagnosis of combined pituitary hormone deficiency (CPHD) requires the presence of growth hormone (GH) deficiency and deficiency of at least one other pituitary hormone. | AR, AD |
POU1F1 | #613038 | |||||||||
HESX1 | #182230 | |||||||||
others | Â | |||||||||
 FIPA | Familial Isolated Pituitary Adenoma | AIP | #102200 | single gene testing | yes |  |  |  | Overlap with MEN1 | AD, somatic mosaicism |
Genetic Thyroid Disorders* | Â | |||||||||
 HCNG | Congenital non-goitrous hypothyroidism | TSHR | #275200 | multigene panel | yes | yes |  |  | Molecularly heterogenous group of disorders. | AD, AR |
SLC5A5 | #274400 | |||||||||
PAX8 | #218700 | |||||||||
others | Â | |||||||||
Glucose and Insulin Homeostasis* | ||||||||||
 MODY | Maturity-Onset Diabetes of the Young type 1 | HNF1A | #600496 | (1. single gene testing) 2. multigene panel 3. CNV analyses | yes | yes |  |  | Currently 11 loci for MODY have been identified. 30–65% of patients carry mutations in HNF1A, 30–50% in GCK, 5–10% in HNF4A. | AD |
Maturity-Onset Diabetes of the Young type 2 | GCK | #125851 | ||||||||
Maturity-Onset Diabetes of the Young type 1 | HNF4A | #125850 | ||||||||
 TNDM | Transient neonatal diabetes mellitus | 6q24 (PLAG1) | #601410 | 1. Methylation-specific test 2. single gene testing or multigene panel | no | yes | yes | yes | TNDM accounts for ~ 50% neonatal diabetes. Other genetic causes include pathogenic variants in KCNJ11 and ABCC8 (see PNDM). | sporadic, AD, paternal inheritance; somatic mosaicism |
KCNJ11 | #610582 | yes | Â | Â | Â | AD | ||||
ABCC8 | #610374 | Â | Â | Â | ; | |||||
 PNDM | Permanent neonatal diabetes mellitus | KCNJ11 | #606176 | multigene panel | yes |  |  |  | KCNJ11 mutations account for 30% of patients, INS 20% and ABCC8 19%.J55 | AD, AR |
ABCC8 | ||||||||||
GCK | ||||||||||
INS | ||||||||||
PDX1 | ||||||||||
 HHF / CHI | Familial hyperinsulinemic hypoglycemia / congenital hyperinsulinism | ABCC8 | #256450 | (1. single gene testing) 2. multigene panel | yes | yes |  | UPD as somatic event in focal type | ABCC8 mutations account for 40–45% of patients. Focal type is due to a paternally inherited ABCC8 or KCNJ11 mutation plus somatic loss of heterozygosity (LOH). | AD, AR |
KCNJ11 | #601820 | |||||||||
others | Â | |||||||||
Genetic Endocrine Tumour Entities* | ||||||||||
 MEN1 | Multiple endocrine neoplasia type 1 | MEN1 | #131100 | 1. single gene testing 2. CNV detection 3. multigene panel | familial: 80–90% single: 65% | 1–4% |  |  | multigene testing after MEN1 analysis: RET, CDKN1B, AIP, CASR, CDC73. | AD |
 MEN2 | Multiple endocrine neoplasia type 2 | RET | #171400 | 1. testing for specific variants (C634R) 2. sequencing of whole gene | 98 > 98% |  |  |  |  | AD |
 MEN3 | Multiple endocrine neoplasia type 3 | #162300 | 1. testing for specific variants (M918T) 2. sequencing of whole gene | 98 > 98% | AD | |||||
 MEN4 | Multiple endocrine neoplasia type 4 | CDKN1B | #620755 | see MEN1 | yes |  |  |  | see MEN1 | AD |
 VHL | von Hippel-Lindau syndrome | VHL | #193300 | 1. single gene sequencing 2. CNV analyses 3. multigene panel | VHL: 89% | VHL: 11% |  |  | broad clinical spectrum and overlap with several disorders. | AD |
 PPGL/PCC | Hereditary Paranglioma- Pheochromocytomas | MAX | #171300 | multigene panel; for specific phenotypes: sequencing of SDHB, SDHD | dependent on the gene: up to 100% | up to 15% |  |  | Broad clinical spectrum and overlap with several disorders. It includes Cushing syndrome. | AD |
SDHA | #614165 | AD | ||||||||
SDHAF2 | #601650 | AD | ||||||||
SDHB | #115310 | AD | ||||||||
SDHC | #605373 | AD | ||||||||
SDHD | #168000 | AD, paternal inheritance | ||||||||
TMEM127 | #171300 | AD | ||||||||
others | Â | Â | Â | Â | ||||||
Growth, Obesity and Metabolism* | ||||||||||
 NS | Noonan syndrome | PTPN11 | #163950 | (1. sequencing of PTPN11) 2. multigene panel | nearly 100% |  |  |  | NS belongs to the group of RASopathies sharing affection of RAS pathway genes and overlapping features. | AD, rarely AR |
SOS1 | #610733 | |||||||||
RAF1 | #611553 | |||||||||
RIT1 | #615355 | |||||||||
others | Â | |||||||||
 BWS | Beckwith-Wiedemann syndrome | 11p15.5 | #130650 | 1. methylation-specific test |  | < 1% |  | 50% | Broad clinical spectrum and overlap with several disorders. | sporadic, rare cases: AD; somatic mosaicism |
2. CDKN1C testing | sporadic: 5% familial: 50% | Â | Â | Â | AD, maternal inheritance | |||||
3. multigene panel | single cases | Â | Â | Â | AD, AR, X-linked | |||||
 SRS | Silver-Russell syndrome | 11p15.5 | #180860 | 1. methylation-specific test |  |  |  | 40% | Broad clinical spectrum and overlap with several disorders | sporadic, rare cases: AD; somatic mosaicism |
2. Microarray | Â | Â | 10% | Â | AD | |||||
3. WES | up to 10% | Â | Â | Â | AD, AR, X-linked | |||||
7 | methylation-specific test | Â | Â | Â | 10% | som. Mosaic | ||||
14q32 | methylation-specific test | Â | Â | Â | 10% | som. Mosaic | ||||
 PWS | Prader-Willi syncdrome | 15q11.2 | #176270 | CNV analyses |  | 75% |  |  | Clinical overlap with several disorders | sporadic; rare cases: AD |
methylation-specific test (also detects 15q11.2 CNVs) |  | 75–80% |  | 20–25% | ||||||
 IGHD | Isolated growth hormone deficiency type 1A | GH1 | #262400 | single gene sequencing | yes |  |  |  | Overlap with disorders caused by mutations in other members of the GH axis. | AR |
Isolated growth hormone deficiency type 1B | GH1 | #612781 | AR | |||||||
Isolated growth hormone deficiency type 2 | GH1 | #173100 | AD | |||||||
Isolated growth hormone deficiency type 4 | GHRHR | #618157 | single gene sequencing | yes | Â | Â | Â | AD | ||
 LS | Laron dwarfism | GHR | #262500 | single gene sequencing | yes |  |  |  | AR | |
GHIP | partial growth hormone insensitivity / Increased responsivness to growth hormone | #604271 | AD | |||||||
 IGF1 deficiency | IGF1 deficiency | IGF1 | #608747 | single gene sequencing | yes |  |  |  | see text | AR |
 IGF1RES | IGF1 resistancy | IGF1R | #270450 | single gene sequencing | yes |  |  |  | see text | AD, AR |
Sex Development and Maturation | ||||||||||
 DSD | Disorders of sex development | SRY, AR,> 30 others |  | 1. Cytogenetics (2. single gene sequencing) 3. multigene panel | yes | yes | yes |  | broad clinical spectrum and overlap. | AD, AR, X-linked |
 TS / UTS | Turner syndrome | 45,X |  | cytogenetics |  |  | 100% |  | see text | de-novo |
 KS | Klinefelter syndrome | 47,XXY |  | cytogenetics |  |  | 100% |  | see text | de-novo |