title: Genetic disorders of pediatric MEN2A patients in the south of Spain.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) is observed in nearly 100 % of patients with multiple endocrine neoplasia type 2A (MEN2A). The gene responsible for MEN2A is the RET proto-oncogene and about 95 % of MEN2A patients have germline mutations in five specific cysteine codons (609, 611, 618, 620 and 634).
  
  
  METHODS
  A retrospective study of children from families with MEN2A in our geographic area was performed. Variables analyzed included demographic data, kinship relations, age at genetic screening, age at prophylactic thyroidectomy, genetic mutation subtype and histological findings. The genetic study consisted in direct molecular analysis by automatic sequencing of RET mutated exon in the studied family.
  
  
  RESULTS
  We performed 13 prophylactic total thyroidectomies from 1997 to 2013, 8 females and 5 males. The mean age at genetic diagnosis was 3.8 years (range 2-5.9). All children belonged to four interconnected families living in the same geographic area and presenting C634Y mutation in all the cases. The mean age at prophylactic thyroidectomy was 5.6 years (range 4-8.5). Histopathological findings demonstrated seven cases of C-cells nodular hyperplasia, one lymphocytic thyroiditis, two without evidence of disease, two micro-carcinomas and one multicentric carcinoma.
  
  
  CONCLUSIONS
  The mutation found in the RET proto-oncogene responsible for MEN2A in pediatric patients in the south of Spain is the C635Y. It is considered a high-risk mutation, associated with an earlier malignant transformation and development of MTC.
authors.affiliation: Department of Pediatric Surgery, Virgen del Rocio University Children's Hospital, Av. Manuel Siurot s/n, Seville, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Martinez-Criado
authors.forename: R M
authors.initials: RM
authors.lastname: Fernandez
authors.forename: S
authors.initials: S
authors.lastname: Borrego
authors.forename: R
authors.initials: R
authors.lastname: Cabello
authors.forename: I
authors.initials: I
authors.lastname: Fernandez-Pineda
mesh_terms: D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013030:Spain; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human