某医院儿童抽动障碍发病因素调查分析

目的:调查儿童抽动障碍发病情况,对其进行研究,了解抽动障碍发病特点及其相关危险因素,为制定预防措施提供来源依据。方法:选取2013年1月至2013年12月上海新华医院中医科就诊的抽动障碍儿童122例,发放问卷调查患儿的一般资料、家族史、既往史、母孕史、发病情况包括发病年龄、就诊年龄、病程进行分析。结果:122例患儿中发病年龄大多集中在10岁以前,为总发病儿童的93.4%,4~6岁的占45.9%,7~9岁的占39.3%。就诊年龄中6岁的占27.9%,6~8岁占39.3%,9~11岁占24.6%。病程6月的占13.1%,6~12月的占27.9%,1~2年的占19.7%,≥2年的占39.3%。其中36.1%有反复呼吸道感染史(OR1,P0.05);29.5%在生产中有轻度窒息(OR1,P0.05);11.5%有流产史(OR1,P0.05);13.1%有家族抽动障碍史(OR1,P(0.05);其中反复呼吸道感染、生产中轻度窒息、家族抽动障碍史是抽动障碍发病的危险因素。结论:儿童抽动障碍发病年龄较早,其起病可能是由多因素相互作用的结果,其中反复呼吸道感染、生产中轻度窒息、家族抽动障碍史是抽动障碍发病的危险因素。     

Family history of cancer and the risk of bladder cancer: A case–control study from Italy

BackgroundA family history of bladder cancer has been associated with the risk of bladder cancer, but quantification of the excess risk in different populations is still a relevant issue. Further, the role of a family history of other cancers on the risk of bladder cancer remains unclear.MethodsWe analyzed data from an Italian case–control study, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) were estimated through unconditional logistic regression models, adjusted for sex, age, study center, year of interview and further for education, smoking and sibling’s number.ResultsThe OR for family history of bladder cancer was 2.13 (95% confidence intervals (95%CIs) 1.02–4.49) from the model with partial adjustment, and 1.99 (95%CI 0.91–4.32) after additional adjustment for smoking and siblings’ number, based on 23 cases (3.3%) and 11 controls (1.7%) with a family history of bladder cancer. The fully adjusted OR was 3.77 when the relative was diagnosed at age below 65 years. Smokers with a family history of bladder cancer had a four-fold increased risk compared to non-smokers without a family history. Bladder cancer risk was significantly increased among subjects with a family history of hemolymphopoietic cancers (OR = 2.97, 95%CI 1.35–6.55). Family history of cancer at other sites showed no significant association with bladder cancer risk.ConclusionThis study confirms an approximately two-fold increased risk of bladder cancer for family history of bladder cancer, and indicates a possible familial clustering of bladder cancer with cancers of the hemolymphopoietic system.     

A study of fluctuating dermatoglyphic asymmetry in the sibs and parents of cleft lip propositi.

Fluctuating asymmetry was studied in cleft lip propositi and their normal sibs and parents. The traits examined were a-b ridge counts and fingerprint patterns. Propositi with a family history of this congenital malformation and their normal sibs and parents were significantly different from the controls for this type of asymmetry. Propositi without a family history and their normal sibs and parents were similar to the controls. These results support the hypothesis that familial and sporadic cases of congenital cleft lip are different entities and give evidence for a genetic mechanism in the parents and sibs of the familial cases that may account for this congenital disorder and, concomitantly, increased fluctuating asymmetry.     

Family history of cancer and non-malignant diseases and risk of childhood acute lymphoblastic leukemia: a Children's Oncology Group Study

Background: Studies of family history of cancer and non-malignant diseases in childhood acute lymphoblastic leukemia (ALL) show inconsistent findings. Most studies show no increased risk with family history of cancer. Non-malignant diseases such as allergic diseases, autoimmune diseases, birth defects and thyroid diseases have been reported to be associated with ALL. Methods: We conducted a case-control study of family history of cancer and selected non-malignant conditions (allergic diseases, autoimmune diseases, birth defects, and thyroid diseases). ALL cases were obtained from Children's Cancer Group institutions from January 1989 to June 1993. Controls were recruited via random digit dialing. Family history for first degree relatives and grandparents of ALL cases and controls was collected by structured telephone questionnaires. Conditional logistical regression was used to calculate odds ratios adjusting for potential confounders. Results: We found a borderline association of ALL and having a family member with a history of cancer in cases (n = 1842) compared to controls (n = 1986) (OR = 0.98, 95%CI = 0.93, 1.00) and an inverse association for esophageal cancer based on small numbers. Family history of food and drug allergies demonstrated a modestly reduced risk (OR = 0.83, 95%CI = 0.73, 0.95) as did family history of rheumatoid arthritis (OR = 0.79, 95%CI = 0.65, 0.96). There were no associations with family history of any autoimmune diseases, immunodeficiencies, birth defects, thyroid diseases and risk of childhood ALL. Conclusions: These results show no association of overall family history of cancer with childhood ALL, while providing additional evidence for an inverse association with family history of allergic disease. Two potentially new associations of ALL with family history of esophageal cancer and rheumatoid arthritis require confirmation in other studies and validation with medical records.     

Family history of non-hematologic cancers among Waldenstrom macroglobulinemia patients: a preliminary study

BackgroundLittle is known about the epidemiology and etiology of Waldenstrom macroglobulinemia (WM). Despite several studies of the relation between family history and B-cell disorders and WM, family history of non-hematologic cancers has not been systematically investigated. We thus examined associations of family history of breast, colorectal, lung, ovarian, and prostate cancers with WM.MethodsAll probands aged 20–79 years with bone marrow biopsy-confirmed diagnosis of WM between May 1, 1999 and January 1, 2010 at the Bing Center for Waldenstrom Macroglobulinemia were eligible for inclusion in our analysis. We reviewed medical records for eligible probands to determine family history of cancer (defined as a cancer diagnosis for ≥1 first-degree relative(s) of the proband). Using expected values constructed from the United States National Health Interview Survey, we estimated age- and race-standardized rate ratios (RRs) for family history of breast, colorectal, lung, ovarian, and prostate cancers by WM subtype.ResultsFamily history of prostate cancer had the largest overall rate ratio (RR = 1.4, 95% confidence limits [CL]: 1.1, 1.7), and among sporadic cases, family history of prostate and breast cancer had the largest rate ratios (prostate: RR = 1.3, 95% CL: 1.1, 1.7; breast: RR = 1.3, 95% CL: 1.2, 1.6).ConclusionOur study suggests that it may be worthwhile to pursue these associations in a case–control study with uniform selection and data collection for cases and controls, and at least some record-based information on family history.     

Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population.

A population-based series of 54 male breast cancer cases from Southern California were analyzed for germ-line mutations in the inherited breast/ovarian cancer genes, BRCA1 and BRCA2. Nine (17%) of the patients had a family history of breast and/or ovarian cancer in at least one first-degree relative. A further seven (13%) of the patients reported breast/ovarian cancer in at least one second-degree relative and in no first-degree relatives. No germ-line BRCA1 mutations were found. Two male breast cancer patients (4% of the total) were found to carry novel truncating mutations in the BRCA2 gene. Only one of the two male breast cancer patients carrying a BRCA2 mutation had a family history of cancer, with one case of ovarian cancer in a first-degree relative. The remaining eight cases (89%) of male breast cancer with a family history of breast/ovarian cancer in first-degree relatives remain unaccounted for by mutations in either the BRCA1 gene or the BRCA2 gene.     

Undetected diabetes and the plastic surgeon

Plastic surgery candidates are generally healthy. Therefore, major postoperative complications are rare. Should they happen, the surgeon should search for possible causes, one of which is undetected diabetes mellitus. Six patients are presented who, based on the individual or family history or the unusual nature of their complications, were suspected of having diabetic tendencies. This experience necessitated our in-depth search into the role of silent or undetected diabetes. This report emphasizes the importance of positive family history of diabetes and the role of glucose tolerance tests on suspected cases. Even with normal glucose tolerance tests, however, some of these patients with a positive family history of diabetes and history of previous infections suffer from deficiencies in the chemotactic immune system. We recommend full discussion of the increased risk of infection and delayed healing with these patients, conservatism during surgical procedures, and prophylactic use of antibiotics perioperatively.     

Synergistic effect between alcohol consumption and familial susceptibility on lung cancer risk among Chinese men

We aimed to examine the effect of alcohol consumption on lung cancer risk stratified by smoking, and to explore whether the impact of alcohol was modified by familial susceptibility to cancer. We recruited 1208 male lung cancer incident cases and 1069 community referents during 2004–2006 and collected their lifetime history of alcohol consumption, cigarette smoking, and family cancer history. Unconditional multivariate logistic regression analysis was performed to estimate the adjusted odds ratio (OR). We tested multiplicative-scale interaction between exposures of interest and examined the additive-scale interaction using synergy index. A moderate association between frequent alcohol consumption and lung cancer was observed among men who had family cancer history (OR = 4.22, 95%CI: 2.46–7.23) after adjustment of smoking and other confounders, while the alcohol effect among men without family history was weak (OR = 1.24, 95%CI: 0.95–1.63) and it became no excess in the never smokers. We observed a consistent synergistic effect between alcohol drinking and family cancer history for all lung cancers and the adenocarcinoma, while there was no multiplicative-scale interaction between the exposures of interest (likelihood ratio test for interaction, p>0.05). Our study revealed a possible synergistic effect between alcohol consumption and familial susceptibility for lung cancer risk; however, this observed possible association needs to be confirmed by future larger analytic studies with more never smoking cases.     

Comparison of Family History and SNPs for Predicting Risk of Complex Disease

The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for studying the predictive ability of family history and single nucleotide polymorphism (SNP)–based methods for assessing risk of polygenic disorders. We show that family history is most useful for highly common, heritable conditions (e.g., coronary artery disease), where it explains roughly 20%–30% of disease heritability, on par with the most successful SNP models based on associations discovered to date. In contrast, we find that for diseases of moderate or low frequency (e.g., Crohn disease) family history accounts for less than 4% of disease heritability, substantially lagging behind SNPs in almost all cases. These results indicate that, for a broad range of diseases, already identified SNP associations may be better predictors of risk than their family history–based counterparts, despite the large fraction of missing heritability that remains to be explained. Our model illustrates the difficulty of using either family history or SNPs for standalone disease prediction. On the other hand, we show that, unlike family history, SNP–based tests can reveal extreme likelihood ratios for a relatively large percentage of individuals, thus providing potentially valuable adjunctive evidence in a differential diagnosis.     

幽门螺杆菌感染并发消化性溃疡的危险因素及预防对策分析

目的:分析幽门螺杆菌感染并发消化性溃疡的危险因素,并实施预防对策。方法:选取我院收治的消化性溃疡的患者201例,对其临床资料进行回顾性分析,分析其危险因素。结果:消化性溃疡患者201例,Hp感染162例,Hp阳性率80.60%,不同类型的消化性溃疡的Hp阳性率比较,差异无统计学意义(P0.05)。单因素分析结果显示,年龄在36-60岁、共食、男性、暴饮暴食、喜爱辛辣食物、吸烟饮酒、个人卫生、家族病史、以往病史,均是消化性溃疡Hp感染的高危因素。进餐习惯、喜欢酸奶、个人卫生均是Hp感染的保护因素,而暴饮暴食、喜爱辛辣食物、年龄、以往病史、吸烟饮酒、家族病史均是Hp感染的危险因素。结论:分餐习惯、喜欢酸奶、个人卫生均是Hp感染的保护因素,而暴饮暴食、喜爱辛辣食物、年龄、以往病史、吸烟饮酒、家族病史是Hp感染的危险因素,进行有针对性的预防可降低疾病发生率。     

Analytical Relationship between Family History and Genetic and Environmental risks,with Application to Female Breast Cancer

It is well established in genetic epidemiology that family history is an important indicator of familial aggregation of disease in a family. A strong genetic risk factor or an environmental risk factor with high familial correlation can result in a strong family history. In this paper, family history refers to the number of first‐degree relatives affected with the disease. Cui and Hopper (Journal of Epidemiology and Biostatistics 2001; 6 : 331–342) proposed an analytical relationship between family history and relevant genetic parameters. In this paper we expand the relationship to both genetic and environmental risk factors. We established a closed‐form formula for family history as a function of genetic and environmental parameters which include genetic and environmental relative risks, genotype frequency, prevalence and familial correlation of the environmental risk factor. The relationship is illustrated by an example of female breast cancer in Australia. For genetic and environmental relative risks less than 10, most of the female breast cancer cases occur between the age of 40 and 60 years. A higher genetic or environmental relative risk will move the peak of the distribution to a younger age. A more common disease allele or more prevalent environmental risk factor will move the peak to an older age. For a proband with breast cancer, it is most likely (with probability ≥80%) that none of her first‐degree relatives is affected with the disease. To enable the probability of having a positive family history to reach 50%, the environmental relative risks must be extremely as high as 100, the familial correlation as high as 0.8 and the prevalence as low as 0.1. For genetic risk alone, even the relative risk is as high as 100, the probability of having a positive family history can only reach about 30%. This suggests that the environmental risk factor seems to play a more important role in determining a strong family history than the genetic risk factor. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study

Objectives To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy.Design Comparison of population based data.Setting Danish longitudinal registers.Subjects The cohort comprised 2.27 million people.Main outcome measures Epilepsy, psychosis, personal birth data.Results We found an increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20 to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people first admitted for epilepsy at later ages.Conclusions There is a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis. The two conditions may share common genetic or environmental causes.     

Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents

von Hippel-Lindau disease (VHL [MIM 193300]) is a heritable autosomal dominant multiple-neoplastic disorder with high penetrance. It is characterized by brain and spinal-cord hemangioblastomas, retinal angiomas, clear-cell renal carcinoma, neuroendocrine tumors and cysts of the pancreas, pheochromocytomas, endolymphatic-sac tumors, and papillary cystadenomas of the epididymis and broad ligament. Although most index cases have a positive family history of VHL, some do not and may represent de novo cases. Cases without a family history of VHL may or may not have a germline mutation in their VHL tumor-suppressor gene. We present two cases of VHL mosaicism. In each of two families, standard testing methods (Southern blot analysis and direct sequencing) identified the germline mutation in the VHL gene of the offspring, but not in their clinically affected parent. Additional methods of analysis of the affected parents' blood detected the VHL-gene mutation in a portion of their peripheral blood lymphocytes. In one case, detection of the deleted allele was by FISH, and, in the second case, the 3-bp deletion was detected by conformational sensitive gel electrophoresis and DNA sequencing of cloned genomic DNA. Mosaicism in VHL is important to search for and recognize when an individual without a family history of VHL has VHL. Patients diagnosed without family histories of the disease have been reported in as many as 23% of kindreds with VHL. Identification of individuals potentially mosaic for VHL will affect counseling of families, and these individuals should themselves be included in clinical screening programs for occult disease.     

家族性肥厚型心肌病一家系的调查分析

目的:分析一家族性肥厚型心肌病的特点。方法:对我院就诊的一肥厚型心肌病大家系进行临床调查研究,分析其临床特点,绘制家系图谱。结果:该家系为连续四代遗传,家系成员共35例,患者11例,猝死3例,死亡2例。有1例患者房颤及脑梗塞,2例患者行永久性起搏器植入术,猝死年龄最小3岁,符合肥厚型心肌病高发病率、高猝死率、发病年龄早等特点。结论:家族性肥厚型心肌病详细的家系调查有助于了解疾病全貌,更好地揭示其遗传规律。     

Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong,China

Background: Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this cancer, but the contributions of family history of other types of cancer and its interaction with environmental factors have not been well characterized. Methods: A total of 1845 incident cases of NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for smoking, consumption of alcohol, salted fish consumption, and demographic factors. Results: A significant association between the risk of NPC and family history of any cancers in first degree relatives was observed, and higher number of affected family member was related to a higher risk (P_trend < 0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46–4.55 for all first degree relatives). The risk of NPC was also positively associated with history of head and neck cancer among parents and lung and breast cancers among siblings. The combination of family history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased the risk for NPC. Conclusions: These results confirm that the risk for NPC increases with family history of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction between family history of cancer, especially NPC, and consumption of salt-preserved fish in the development of NPC was also identified.     

The Scarborough Glaucoma Survey

A glaucoma screening survey was carried out in Scarborough, Ontario, to detect previously unsuspected cases of the disease.General practitioners were employed to perform Schiotz tonometry. Suspected cases were further tested with applanation tonometry and tonography with water drinking.Of the 17,968 persons examined, 999 had a family history of glaucoma. Forty-one of these had obvious clinical glaucoma. The use of Schiotz tonometry plus applanation tonometry in individuals with a positive family history uncovered 463 suspected of having glaucoma. Tonography with water drinking revealed 348 persons with abnormal findings. Of this number, 228 had clinical glaucoma and 120 preclinical glaucoma.Mass screening by tonometry was found to be valuable in detecting glaucoma in the early stages. In most instances, blindness from this disease can be prevented by early diagnosis.     

DICER1 mutations in twelve Chinese patients with pleuropulmonary blastoma

Our aim is to examine the impact of DICER1 mutations on the pathogenesis of pleuropulmonary blastoma(PPB) by evaluating the mutation frequency and investigating the family history of Chinese patients with PPB. The family histories of 12 children with PPB recruited consecutively were surveyed. Blood samples from patients and their first-degree relatives were tested for DICER1 mutations. Whole-genome sequencing of blood samples and formalin-fixed and paraffin-embedded(FFPE) tumor tissue was performed in one family with twins. Twelve patients with PPB included six type II and six type III cases. Seven of the12 patients harbored DICER1 mutations, six of which were frameshift or nonsense mutations. Another case carried a germline DICER1 mutation affecting the splice site. FFPE sample had a nonsense mutation in TDG and missense mutations in DICER1.In addition, two cases with DICER1 mutations were found to have lung cysts preceding the diagnosis of PPB. Furthermore, one patient had a family history remarkable for thyroid diseases. Our results indicate that the germline mutation frequency in Chinese patients with PPB is similar to the ones reported for patients from USA, UK, and Japan. Moreover, our study strongly suggests that investigating the family history and detecting germline DICER1 mutations might be of benefit to increasing awareness and improving the accuracy of the differential diagnosis of PPB from non-malignant lung cysts.     

Effect of misreported family history on Mendelian mutation prediction models

People with familial history of disease often consult with genetic counselors about their chance of carrying mutations that increase disease risk. To aid them, genetic counselors use Mendelian models that predict whether the person carries deleterious mutations based on their reported family history. Such models rely on accurate reporting of each member's diagnosis and age of diagnosis, but this information may be inaccurate. Commonly encountered errors in family history can significantly distort predictions, and thus can alter the clinical management of people undergoing counseling, screening, or genetic testing. We derive general results about the distortion in the carrier probability estimate caused by misreported diagnoses in relatives. We show that the Bayes factor that channels all family history information has a convenient and intuitive interpretation. We focus on the ratio of the carrier odds given correct diagnosis versus given misreported diagnosis to measure the impact of errors. We derive the general form of this ratio and approximate it in realistic cases. Misreported age of diagnosis usually causes less distortion than misreported diagnosis. This is the first systematic quantitative assessment of the effect of misreported family history on mutation prediction. We apply the results to the BRCAPRO model, which predicts the risk of carrying a mutation in the breast and ovarian cancer genes BRCA1 and BRCA2.     

VERNAL CONJUNCTIVITIS AS AN ATOPIC DISEASE

In a study of 30 cases of vernal conjunctivitis, antibodies to grass pollen were demonstrated in 16 of 29 patients tested by direct skin tests, in 11 of 30 tested by the Prausnitz-Kustner method and in 22 of 30 by the bis-diazotized benzidine hemagglutination method.A personal history of major atopic disease was found in 13 of 27 patients, and a family history of atopic disease in 16 of 26 patients questioned.Conjunctival eosinophilia was found in all cases. Results of the study indicated that vernal conjunctivitis is an atopic disease.     

Case-control and case-only designs with genotype and family history data: estimating relative risk, residual familial aggregation, and cumulative risk

In case-control studies of inherited diseases, participating subjects (probands) are often interviewed to collect detailed data about disease history and age-at-onset information in their family members. Genotype data are typically collected from the probands, but not from their relatives. In this article, we introduce an approach that combines case-control analysis of data on the probands with kin-cohort analysis of disease history data on relatives. Assuming a marginally specified multivariate survival model for joint risk of disease among family members, we describe methods for estimating relative risk, cumulative risk, and residual familial aggregation. We also describe a variation of the methodology that can be used for kin-cohort analysis of the family history data from a sample of genotyped cases only. We perform simulation studies to assess performance of the proposed methodologies with correct and mis-specified models for familial aggregation. We illustrate the proposed methodologies by estimating the risk of breast cancer from BRCA1/2 mutations using data from the Washington Ashkenazi Study.