Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A(MEN 2A)family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma ( MTC).Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members(p.C634R), which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years(ranging from 19 years to 65 years) and the mean maximum diameter of MTC was 2.3 cm(ranging from 0.7 cm to 5.2 cm). Among them 3 members had palpable neck masses (1 case with diarrhea).Right total thyroidectomy +right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy +bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy +bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom ( PHEO) underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient( T3N 1bM 0-1) underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively (T1N 1bM0 and T2N 1bM0), and the other one patient was closely monitored and followed up for 22 months(T2N 1b M0).Moreover, The calcitonin levels dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .

OBJECTIVETo explore the clinical characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A).

METHODSComprehensive medical history was obtained for 5 members from a 3-generation family from southern China. Clinical investigations have included biochemical testing, imaging, and screening of germline RET proto-oncogene mutations.

RESULTSGenetic screening has revealed a missense mutation at codon 618(TGC>CGC) of exon 10 in 3 patients(p.C618R), which was consistent with their clinical manifestations. For the 3 individuals, the age at diagnosis was 21, 26 and 36 yr, and the maximum diameter of medullary thyroid carcinoma was 22, 25 and 39 cm, respectively. The 36-year-old female patient initially underwent right total thyroidectomy plus right neck lymph node dissection. Four years later, she again underwent left adrenal tumorectomy and left total thyroidectomy plus left neck lymph node dissection. The 21-year-old male patient underwent right total thyroidectomy plus right modified neck dissection. The follow-up was respectively 146 and 26 months following the initial operation. Two patients still presented elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid masses on imaging examination. The 26-year-old female patient, who presented bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy.

CONCLUSIONCombined family survey and RET gene screening can facilitate early diagnosis and surgical treatment to improve the prognosis.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Carcinoma, Neuroendocrine ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Multiple Endocrine Neoplasia Type 2a ; enzymology ; genetics ; Mutation, Missense ; Pedigree ; Proto-Oncogene Proteins c-ret ; genetics ; Thyroid Neoplasms ; enzymology ; genetics ; Young Adult

OBJECTIVE: To explore the pathological characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A) with cutaneous lichen amyloidosis (CLA). METHODS: Clinical data of 51 members from 7 unrelated pedigrees of MEN2A-CLA were collected. Systemic clinical investigations including biochemical testing, imaging examination, germline RET variant screening and histopathological examination were carried out. RESULTS: RET gene variants were detected in 28 patients with MEN2A (C634G/F/R/S/W and C611Y) including 12 males and 16 females, with the mean age of diagnosis being (41.1 ± 18.3) years old, which were consistent with their clinical manifestations. The incidence of medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), hyperparathyroidism (HPTH) and CLA among 28 MEN2A patients were 89.3%, 28.6%, 7.1% and 28.6%, respectively. Comparison of the incidence of MTC/PHEO/HPTH and CLA between C611Y and C634G/F/R/S/W, only PHEO and CLA in C611Y were lower than those in C634G/F/R/S/W (P < 0.05; P < 0.05). Among 8 patients with CLA, the male to female ratio was 2 : 6. The clinical features included pruritus in the interscapular region and presence of dry, thickened, scaly, brown pigment, clustered or desquamate-like plaques. The mean onset age of CLA [(18.4 ± 4.6) years] versus the mean age at diagnosis of CLA or MEN2A were significantly different (P < 0.001; P < 0.001). CONCLUSION MEN2A-CLA may be the early clinical manifestation of MEN2A and most frequently occurred along with RET-C634 variant. To facilitate the recognition of MEN2A-CLA, to combine family investigation and screening of RET variant are helpful for early diagnosis and standardized treatment, which can improve the long-term outcome of MEN2A-specific tumors.
Adolescent ; Adrenal Gland Neoplasms ; Adult ; Amyloidosis, Familial ; Carcinoma, Neuroendocrine ; China ; Female ; Humans ; Lichens ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Pheochromocytoma ; Proto-Oncogene Proteins c-ret/genetics* ; Skin Diseases, Genetic ; Thyroid Neoplasms/genetics* ; Young Adult

PURPOSE: Although varicella outbreakes have frequently occured, the epidemiology of varicella in Korea has not well been delineated. Furthermore without enough investigation with regard to safety and efficacy of varicella vaccine in Korean population, the vaccine has begun to be used in healthy children. Therefore the authors analized the clinical features of patients diagnosed of varicella to aid in understanding the epidemiology of varicella in Korea, and also compared the difference depending on varicella vaccination status. METHODS: The study population consisted of 1154 otherwise healthy patients diagnosed of varicella by six private pediatricians (5 in Seoul and 1 in Incheon) from March 1994 to February 1996. The information pertaining to clinical features of varicella was obtained through questionnaires answered by pediatricians. RESULTS: 1) Among the total 1154 patients, sex ratio was 1.2:1 with male predominance. The average age was 4.1+/-2.5 years old with the range of 1 month to 15 years of age. One thousand and thirty patients (89.2%) were younger than 6 years old and 126 patients (10.9%) were younger than 1 year old. 2) Occurrence of varicella was reported every month during the study period and peak in June, July, and November to January. 3) Two hundreds and eight-four patients (24.6%) had a history of previous varicella vaccination. 4) Four hundreds and fifty-five patients (53.3%) had a history of exposure to patients with varicella and the mean incubation period was 13.7+/-4.1 days with no difference according to varicella vaccination status. 5) Prodromal symptoms were reported from 615 patients (53.3%) with temperature elevation being most frequent. Except for temperature elevation, occurrence of all other prodromal symptoms was not different between unvaccinated and vaccinated patients. 6) Duration of new rash development was 3.9+/-1.3 days with the range of 1 to 9 days and longer in unvaccinated patients (4.1+/-1.2 days) compared to vaccinated patients (3.1+/-1.1 days). Atypical rash was observed in 144 patients (12.5%) and more frequently among unvaccinated patients. 7) Sixty-eight patients suffered from complications which were skin infection (49), conjunctivitis (20), neurologic complication (1), and pneumonia (1), with no difference between unvaccinated and vaccinated patients. CONCLUSIONS: The current study is reporting, for the first time, the epidemiologic features of varicella in Korea. Bedsides, the result of the study, illustrating that 1/4 of the patients reported to have varicella were vaccinated with varicella vaccine, indicates the necessity of the investigation for the safety and efficacy of the vaccine in Korean population.
Chickenpox Vaccine ; Chickenpox* ; Child ; Conjunctivitis ; Epidemiology* ; Exanthema ; Humans ; Korea* ; Male ; Pneumonia ; Prodromal Symptoms ; Surveys and Questionnaires ; Seoul ; Sex Ratio ; Skin ; Vaccination