Clinical characteristics and genetic screening of an extended family with MEN2A.
MEN-2A is characterized by medullary thyroid carcinoma (MTC) with pheochromocytoma and sometimes parathyroid adenoma. In affected members of the family, the risk of MTC is about 100%. Biochemical screening allows tumors to be detected early but even at this stage treatment is not always curative. Missense mutations in exon 10 and 11 of the RET proto-oncogene are associated with MEN-2A. Early detection of this mutation by DNA analysis allows the identification of the carriers of the gene. We performed genetic screening in 88 members of an extended family with MEN-2A and found 18 members positive for RET mutation (Cys634Gly). Only three of these 18 RET positive cases had a previous diagnosis of medullary cancer and/or pheochromocytoma. Up to now, 12 of the RET positive cases have undergone thyroidectomy. There was extended disease with cervical lymph node metastasis in 6 of them, bilateral medullary microcancer in 3 and c-cell hyperplasia in the remaining 3. Three of the 18 RET positive patients had also pheochromocytoma. Primary hyperparathyroidism was present in only one patient. The mean age of diagnosis of medullary cancer was between 25-50 yr and mean age of death was between 35-95 yr in affected members of the family. The family had many other affected members in other cities in Turkey and in other countries throughout the world from Australia to the Netherlands. So this family is perhaps one of the most extended families with MEN-2A.
Algün
E
E
Yüzüncü Yil University, School of Medicine, Department of Endocrinology, Van, Turkey. ekremalgun@hotmail.com
Abaci
N
N
Kösem
M
M
Kotan
C
C
Köseoğlu
B
B
Boztepe
H
H
Sekeroğlu
R
R
Aslan
H
H
Topal
C
C
Ayakta
H
H
Uygan
I
I
Alagöl
F
F
Erginel-Unaltuna
N
N
Aksoy
H
H
D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D029721:Drosophila Proteins; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014421:Turkey
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila