IllnessMultiple endocrine tumors, differential diagnosis

NGS +

[Sanger]

Multiple endocrine neoplasms (MEN) are a group of diseases affecting the hormone-producing glands. In MEN, neoplasms typically occur in at least two endocrine glands; tumors may also develop in other organs and tissues. These growths may be benign or malignant. The major forms are referred to as MEN types 1, 2, and 4. These types differ in the genes involved, the type of hormones produced and the characteristic signs and symptoms. Type 1 often involves tumors of the parathyroid glands, pituitary gland and pancreas, causing overproduction of hormones and leading to hyperparathyroidism with kidney stones, osteoporosis, hypertension and weakness. Type 2 includes medullary thyroid carcinoma and eventually pheochromocytoma with pernicious hypertension. Type 2 is divided into subtypes 2A, 2B and familial medullary thyroid carcinoma. The subtypes differ in their characteristic signs and risk for specific tumors. Within a family, symptoms are relatively uniform. Type 4 has similar symptoms to type 1, but it is caused by mutations in a different gene, with hyperparathyroidism being the most common feature, followed by tumors of the pituitary, other endocrine glands and other organs. Mutations in the MEN1, RET and CDKN1B genes can cause types 1, 2 and 4 usually have autosomal dominant inheritance. A few cases are due to novel mutations in the respective genes. The genetic differential diagnosis of multiple endocrine tumors includes an even broader spectrum of quite different genes compared with MEN usually also with autosomal dominant inheritance. The DNA diagnostic yield using this panel depends on the tumor entities and is still unknown in total. Therefore, an inconspicuous genetic finding does not imply exclusion of the suspected clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1257/

https://www.ncbi.nlm.nih.gov/books/NBK1538/

https://www.ncbi.nlm.nih.gov/books/NBK1548/

https://www.ncbi.nlm.nih.gov/books/NBK97965/

• Alias: Adenomatosis, familial endocrine
• Alias: Endocrine neoplasia, multiple
• Alias: Familial endocrine adenomatosis
• Alias: MEN
• Alias: Multiple endocrine adenomatosis
• Alias: Multiple endocrine neoplasms
• Allelic: Acrodysostosis 1, with/-out hormone resistance (PRKAR1A)
• Allelic: Angiofibroma, somatic (MEN1)
• Allelic: Basal cell carcinoma 7 (TP53)
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Breast cancer, somatic (TP53)
• Allelic: Cardiomyopathy, dilated, 1GG (SDHA)
• Allelic: Central hypoventilation syndrome, congenital (RET)
• Allelic: Choroid plexus papilloma (TP53)
• Allelic: Colorectal cancer (TP53)
• Allelic: Deafness, AR 12 (CDH23)
• Allelic: Epilepsy idiopathic generalized, susceptibility to (CASR)
• Allelic: Erythrocytosis, familial, 2 (VHL)
• Allelic: Gastrointestinal stromal tumor (SDHB, SDHC)
• Allelic: Glioma susceptibility 1 (TP53)
• Allelic: Glioma susceptibility 2 (PTEN)
• Allelic: Hemangioblastoma, cerebellar, somatic (VHL)
• Allelic: Hepatocellular carcinoma, somatic (TP53)
• Allelic: Hirschsprung disease, protection against + susceptibility to, 1 (RET)
• Allelic: Hypocalcemia, AD (CASR)
• Allelic: Hypocalcemia, AD, with Bartter syndrome (CASR)
• Allelic: Hypocalciuric hypercalcemia, type I (CASR)
• Allelic: Leigh syndrome (SDHA)
• Allelic: Leukemia, juvenile myelomonocytic (NF1)
• Allelic: Lipoma, somatic (MEN1)
• Allelic: Macrocephaly
• Allelic: Meningioma (PTEN)
• Allelic: Mitochondrial respiratory chain complex II deficiency (SDHA, SDHD)
• Allelic: Myxoma, intracardiac (PRKAR1A)
• Allelic: Nasopharyngeal carcinoma, somatic (TP53)
• Allelic: Osteosarcoma (TP53)
• Allelic: Pancreatic cancer, somatic (TP53)
• Allelic: Renal cell carcinoma {disease} [MONDO:0005086, panelapp] (CDKN2B)
• Allelic: Renal cell carcinoma, somatic (VHL)
• Allelic: Usher syndrome, type 1D (CDH23)
• Allelic: Usher syndrome, type 1D/F digenic (CDH23)
• Allelic: Watson syndrome (NF1)
• Adrenal adenoma, somatic (MEN1)
• Adrenocortical carcinoma, pediatric (TP53)
• Adrenocortical tumor, somatic (PRKAR1A)
• Autism syndrome (PTEN)
• Carcinoid tumor of lung (MEN1)
• Carney complex, type 1 (PRKAR1A)
• Cowden syndrome 1 (PTEN)
• Fumarase deficiency (FH)
• Hyperparathyroidism, familial primary (CDC73)
• Hyperparathyroidism, neonatal (CASR)
• Hyperparathyroidism-jaw tumor syndrome (CDC73)
• Leiomyomatosis + renal cell cancer (FH)
• Lhermitte-Duclos syndrome (PTEN)
• Li-Fraumeni syndrome (TP53)
• Medullary thyroid carcinoma (RET)
• Multiple endocrine neoplasia 1 [panelapp] (CDKN1A, CDKN2B, CDKN2C)
• Multiple endocrine neoplasia I (MEN1)
• Multiple endocrine neoplasia IIA + IIB (RET)
• Multiple endocrine neoplasia IV (CDKN1B)
• Neuroendocrine cancer [panelapp] (FH)
• Neurofibromatosis, familial spinal (NF1)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Paraganglioma + gastric stromal sarcoma (SDHB, SDHC, SDHD)
• Paragangliomas 1, with/-out deafness (SDHD)
• Paragangliomas 2 (SDHAF2)
• Paragangliomas 3 (SDHC)
• Paragangliomas 4 (SDHB)
• Paragangliomas 5 (SDHA)
• Parathyroid adenoma with cystic changes (CDC73)
• Parathyroid adenoma, somatic (MEN1)
• Parathyroid carcinoma (CDC73)
• Pheochromocytoma (RET, SDHB, SDHD, VHL)
• Pheochromocytoma, susceptibility to (MAX, TMEM127)
• Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
• Pituitary adenoma 1, multiple types (AIP)
• Pituitary adenoma 2, GH-secreting (GPR101)
• Pituitary adenoma 5, multiple types (CDH23)
• Pituitary adenoma predisposition (AIP)
• Von Hippel-Lindau syndrome (VHL)
• Zollinger-Ellison syndrome (RPRG1A, CDKN1B)