Details of Disease

General Information of Disease (ID: DIS7D3W2)

• Disease Name: Multiple endocrine neoplasia type 2A
• Synonyms: thyroid carcinoma, familial medullary; men-2A syndrome; pheochromocytoma and amyloid producing medullary thyroid carcinoma; multiple endocrine neoplasia, type IIA; multiple endocrine neoplasia, type 2A; pheochromocytoma and amyloid-producing medullary thyroid carcinoma; ptc syndrome; multiple endocrine neoplasia II; multiple endocrine neoplasia IIA; men type II; MEN2A; multiple endocrine neoplasia type 2A; men 2A; multiple endocrine neoplasia, type II; men type 2a; multiple endocrine adenomatosis type 2a; Sipple syndrome; multiple endocrine adenomatosis, type II; multiple endocrine adenomatosis type 2A; multiple endocrine adenomatosis type II; MEA type 2a; multiple endocrine neoplasia type II; MEA type II
• Definition: Multiple endocrine neoplasia 2A (MEN2A) syndrome is a form of MEN2 characterized by medullary thyroid carcinoma (MTC) in combination with pheochromocytoma and primary mild hyperparathyroidism resulting from hyperplasia or adenoma of the parathyroid cells.
• Disease Hierarchy:
  DISPQ4Y5: Multiple endocrine neoplasia type 2
  DIS3HIWD: Autosomal dominant disease
  DIS7D3W2: Multiple endocrine neoplasia type 2A
• Disease Identifiers:
  MONDO ID: MONDO_0008234
  MESH ID: D018813
  UMLS CUI: C0025268
  OMIM ID: 171400
  MedGen ID: 9958
  Orphanet ID: 247698
  SNOMED CT ID: 721188000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CALCA	TTVSFJW	Strong	Biomarker	[1]
IL31RA	TT9HPX0	Strong	Genetic Variation	[2]
ITGB1	TTBVIQC	Strong	Biomarker	[3]
MAZ	TT059DA	Strong	Biomarker	[4]
NCOA4	TT8OY02	Strong	Genetic Variation	[5]
OSMR	TTAH0KM	Strong	Genetic Variation	[2]
SDHD	TTVH9W8	Strong	Genetic Variation	[6]
RET	TTY0WT7	Definitive	Autosomal dominant	[7]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC18A1	DTM953D	Strong	Altered Expression	[8]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MT1A	DE5ME8A	Strong	Biomarker	[9]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
RYK	OTZ3WWZH	Limited	Genetic Variation	[10]
HNRNPA3	OT4O4NFS	Strong	Genetic Variation	[11]
HNRNPF	OTSMBXMF	Strong	Biomarker	[12]
MCAT	OTH07FIW	Strong	Biomarker	[13]
MCPH1	OTYT3TT5	Strong	Biomarker	[13]
MEN1	OTN6U6V0	Strong	Genetic Variation	[14]
RBP3	OTIWM4GT	Strong	Genetic Variation	[15]
SDHB	OTRE1M1T	Strong	Altered Expression	[16]
SDHC	OTC8G2MX	Strong	Biomarker	[17]
SIN3A	OTM8OZWV	Strong	Biomarker	[18]
RET	OTLU040A	Definitive	Autosomal dominant	[7]

References

• [1] Bilateral Medullary Thyroid Carcinoma in a 3-Year-Old Female Patient with Multiple Endocrine Neoplasia 2A Syndrome Undergoing Prophylactic Thyroidectomy: Should Current Guidelines Be Revised?.Eur Thyroid J. 2018 Oct;7(5):267-271. doi: 10.1159/000489170. Epub 2018 May 25.
• [2] The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2A with Cutaneous Lichen Amyloidosis in Ethnic Han Chinese.Cancer Invest. 2018 Feb 7;36(2):141-151. doi: 10.1080/07357907.2018.1430813. Epub 2018 Feb 8.
• [3] A new polymorphic marker (D10S97) tightly linked to the multiple endocrine neoplasia type 2A (MEN2A) locus.Hum Genet. 1993 Jan;90(5):516-20. doi: 10.1007/BF00217451.
• [4] Transcriptional regulation of phenylethanolamine N-methyltransferase in pheochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.Ann N Y Acad Sci. 2006 Aug;1073:241-52. doi: 10.1196/annals.1353.026.
• [5] Expression of the RET oncogene induces differentiation of SK-N-BE neuroblastoma cells.Cell Growth Differ. 1995 Nov;6(11):1387-94.
• [6] Over-representation of the G12S polymorphism of the SDHD gene in patients with MEN2A syndrome.Clinics (Sao Paulo). 2012;67 Suppl 1(Suppl 1):85-9. doi: 10.6061/clinics/2012(sup01)15.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2.Eur J Endocrinol. 2005 Oct;153(4):551-63. doi: 10.1530/eje.1.01987.
• [9] MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics.Fam Cancer. 2016 Oct;15(4):625-33. doi: 10.1007/s10689-016-9892-6.
• [10] A potential pathogenetic mechanism for multiple endocrine neoplasia type 2 syndromes involves ret-induced impairment of terminal differentiation of neuroepithelial cells.Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7933-7. doi: 10.1073/pnas.93.15.7933.
• [11] A 1.5-megabase yeast artificial chromosome contig from human chromosome 10q11.2 connecting three genetic loci (RET, D10S94, and D10S102) closely linked to the MEN2A locus.Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):492-6. doi: 10.1073/pnas.90.2.492.
• [12] Identification and characterization of a gene at D10S94 in the MEN2A region.Genomics. 1992 Jun;13(2):344-8. doi: 10.1016/0888-7543(92)90251-m.
• [13] Plasma and tumor dopamine-beta-hydroxylase activity in patients with familial pheochromocytomas.Metabolism. 1978 Dec;27(12):1797-802. doi: 10.1016/0026-0495(78)90266-4.
• [14] The genetics of neuroendocrine tumors.Semin Oncol. 2013 Feb;40(1):37-44. doi: 10.1053/j.seminoncol.2012.11.005.
• [15] Genomic and yeast artificial chromosome long-range physical maps linking six loci in 10q11.2 and spanning the multiple endocrine neoplasia type 2A (MEN2A) region.Genomics. 1993 Sep;17(3):611-7. doi: 10.1006/geno.1993.1380.
• [16] An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis.Lancet Oncol. 2009 Aug;10(8):764-71. doi: 10.1016/S1470-2045(09)70164-0. Epub 2009 Jul 1.
• [17] Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma. J Clin Endocrinol Metab. 2004 Nov;89(11):5694-9. doi: 10.1210/jc.2004-0769.
• [18] Sin3a acts through a multi-gene module to regulate invasion in Drosophila and human tumors.Oncogene. 2013 Jun 27;32(26):3184-97. doi: 10.1038/onc.2012.326. Epub 2012 Aug 13.