Summary
We report on incidental findings during family screening of two kindreds with multiple endocrine neoplasia type IIa. Pheochromocytoma and medullary thyroid carcinoma of considerable size were detected. The results underline the importance of early diagnosis of the syndrome, since the afflicted may be almost or wholly asymptomatic. High resolution chromosome banding studies were carried out in both families, but no abnormality was found. Linkage analysis using DNA markers closely related to the chromosomal locus at chromosome 10 was carried out and was positive in two asymptomatic offspring of one family, whereas the markers were not informative in a second family. We recommend early linkage analysis for establishing the genetic status in offspring of multiple endocrine neoplasia type IIa families to identify for further screening those who are predicted to be gene carrier.
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Abbreviations
- MEN:
-
Multiple endocrine neoplasia
- Q-Banding=QFQ-Banding:
-
Q-bands labeled by quinacrine florescence using quinacrine staining
- R-Banding=RBA-Banding:
-
R-bands labeled by BrdU incorporation and acridine-orange staining
- BrdU:
-
Bromodeoxyuridine
- RFLP:
-
Restriction fragment length polymorphism
- MIBG:
-
Metaiodobenzylguanidine
References
Butler MG, Repaske DR, Joseph GM, Phillips JA (1987) High resolution chromosome and DNA analysis in multiple endocrine neoplasia type II syndrome. Cancer Genet Cytogenet 24:129–135
Caspersson T, Zech L, Johannsson C, Modest EJ (1970) Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 30:215–227
Church GM, Gilbert W (1984) Genomic sequencing. PNAS 81:1991–1995
Duncan AM, Greenberg CR (1986) Absence of chromosomal instability in one kindred with multiple endocrine neoplasia type IIa. Cancer Genet Cytogenet 22:109–112
Feinberg AP, Vogelstein B (1984) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:266–267
Gagel RF, Tashjian AH, Cummings T, Papathanasopoulos N, Kaplan MM, DeLellis RA, Wolfe HJ, Reichlin S (1988) The clinical outcome of prospective screening for multiple endocrine neoplasia type IIa — an 18-year experience. N Engl J Med 318:478–484
Haak HR, Nieuwenhuijzen Kruseman AC (1987) Characteristics of a family with the MEN IIa syndrome. Henry Ford Hosp Med J 35:104–106
Hadden DR, O'Reilly F, Kennedy L, Russell C (1987) Multiple endocrine neoplasia type IIa: a Northern Ireland and Australian family. Henry Ford Hosp Med J 35:107–109
ISCN (1985) An international system for human cytogenetic nomenclature. Harnden DG, Klinger HP (eds), published in collaboration with Catogenet Cell Genet (Karger, Basel 1985); also in Birth Defects: Original article series, vol 21, no 1 (March of Dimes Birth Defects Foundation, NY, 1985)
Keiser HR, Beaven MA, Doppman J, Wells S, Buja LM (1973) Sipple's syndrome: medullary thyroid carcinoma, pheochromocytoma and parathyroid disease. Ann Int Med 78:561–579
Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones Jr HW, Rary JM (1977) Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. PNAS 74:1245–1249
Liou GI, Fong S-L, Beattie WG, Cook RG, Leone J, Landers RA, Alvarez RA, Wang C, Li Y, Bridges CDB (1986) Bovine interstitial retinol-binding protein (IRBP) — isolation and sequence analysis of cDNA clones, characterization and in vitro translation of mRNA. Vision Res 26:1645–1654
Mathew CGP, Chin KS, Easton DF, Thorpe K, Carter C, Liou GI, Fong SL, Bridges CDB, Haak H, Nieuwenhuijzen Kruseman AC, Schifter S, Hansen HH, Telenius H, Telenius-Berg M, Ponder BAJ (1987) A linked genetic marker for multiple endocrine neoplasia type IIa on chromosome 10. Nature 328:527–528
Nakamura Y, Carlson N, Krapcho K, Gill J, O'Connell P, Leppert M, Lathrop GM, Latonel J-M, White R (1988) Isolation and mapping of a polymorphic DNA sequence pMCK2 on chromosome 10 (DIOSI5). NAR 16:374
Pfeiffer RA (1974) Cell cultures from blood and bone marrow. In: Schwarzacher HG, Wolf U (eds) Methods in human cytogenetics. Springer Verlag, New York
Ponder BAJ, Ponder MA, Coffey R, Pembrey ME, Gagel RF, Telenius-Berg M, Semple P, Easton DF (1988) Risk estimation and screening in families of patients with medullary thyroid carcinoma. Lancet: 397–400
Schempp W, Meer B (1983) Cytologic evidence for three human X-chromosomal segments escaping inactivation. Hum Genet 63:171–174
Simpson NE, Kidd KK, Goodfellow PJ, McDermid H, Myers S, Kidd JR, Jackson CE, Duncan AMV, Farrer LA, Brasch K, Castiglione C, Genel M, Gertner J, Greenberg CR, Gusella JF, Holden JJA, White BN (1987) Assignment of multiple endocrine neoplasia type IIa to chromosome 10 by linkage. Nature 328:528–530
Sobol H, Salvetti A, Bonnardel C, Lenoir GM (1988) Screening multiple endocrine neoplasia IIa families using DNA markers. Lancet:62
Vandenplas S, Wiid I, Grobler-Rabie A, Brebner K, Rikkets M, Wallis G, Bester A, Boyd C, Mathew CGP (1984) Blot hybridization analysis of genomic DNA. J Med Genet 21:164–172
Van Dyke DL, Jackson CE, Baku VR (1981) Multiple endocrine neoplasia type (MEN 2); an autosomal dominant syndrome with a possible chromosome 20 deletion. Am J Hum Genet 33:69a
Zattarale A, Stabile M, Nunziata V, DiGiovanni G, Vecchione R, Ventruto V (1984) Multiple endocrine neoplasia type 2 (Sipple's syndrome): clinical and cytogenetic analysis of a kindred. J Med Genet 21:108–111
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Neumann, H.P.H., Müller, O.A., Ponder, B.A.J. et al. Early diagnosis of multiple endocrine neoplasia type IIa. Klin Wochenschr 67, 951–956 (1989). https://doi.org/10.1007/BF01721424
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DOI: https://doi.org/10.1007/BF01721424