Early onset of medullary thyroid carcinoma in a kindred with multiple endocrine neoplasia type iia associated with cutaneous lichen amyloidosis.
OBJECTIVE
To describe the molecular characterization of a kindred affected by the rare variant of multiple endocrine neoplasia type IIA (MEN IIA) associated with cutaneous lichen amyloidosis and to discuss the clinical implications in the management of this syndrome.


METHODS
A kindred with four affected family members was identified, and DNA analysis was performed by sequencing exon 11 of the RET proto-oncogene. Presymptomatic genetic screening was offered to all first-degree relatives.


RESULTS
Sequencing analysis of the RET proto-oncogene revealed a Cys634Trp (TGC->TGG) mutation in all clinically affected family members and in an asymptomatic 5-year-old child who, after thyroidectomy, was found to have multicentric medullary thyroid carcinoma and C-cell hyperplasia. A Gly691Ser (GGT->AGT) polymorphism was also detected in this family but did not segregate with the disease.


CONCLUSIONS
To our knowledge, this is the earliest detection of medullary thyroid carcinoma reported thus far in a kindred with MEN IIA associated with cutaneous lichen amyloidosis, and this finding suggests that prophylactic thyroidectomy, in kindreds with this variant, should be performed before the age of 5 years.
Lemos
Manuel C
MC
Serviço de Endocrinologia, Diabetes e Metabolismo, Hospitais da Universidade de Coimbra, Coimbra, Portugal.
Carrilho
Francisco
F
Rodrigues
Fernando J
FJ
Santos
Paulo
P
Carvalheiro
Manuela
M
Ruas
Manuel A
MA
Regateiro
Fernando J
FJ
D000328:Adult; D000686:Amyloidosis / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000601:surgery; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D006801:Humans; D008010:Lichen Planus / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
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