First-degree Relatives Of Index Patients Research Articles

SAT309 Clinical And Genetic Profiling Of Patients With Multiple Endocrine Neoplasia Type 2 Syndrome And Screening for Medullary Thyroid Carcinoma In Asymptomatic First-degree Relatives

Abstract Disclosure: K. Kumar P: None. Y. Gupta: None. A. Goyal: None. D. Kandasamy: None. N. Tandon: None. Background: Multiple endocrine neoplasia type 2 (MEN2) syndrome is a rare disorder with autosomal dominant inheritance, characterised by the presence of two of the following three endocrine manifestations: medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT) [1-2]. There is a paucity of data on clinical and genetic profile of MEN2 syndrome in the Indian subcontinent. Objectives: We aimed to evaluate the clinical and genetic profile of patients with MEN2 syndrome and perform screening for MTC among asymptomatic family members with serum calcitonin. Materials and Methods: This was an ambispective study conducted in the Department of Endocrinology at AIIMS New Delhi, involving diagnosed patients of MEN2 syndrome between January 2016 and December 2022. Results: We evaluated a total of 24 families with MEN2 syndrome comprising 61(MEN2A, n=56; MEN2B, n=5) patients, 18 patients were diagnosed as index cases. Data were derived retrospectively for 46 patients (MEN2A, n=43 MEN2B, n=3) and prospectively for 15 patients (MEN2A, n=13; MEN2B, n=2). The mean age at presentation of MEN2A and MEN2B were 28.6 ± 13.52 years and 22 ± 4.44 years, respectively. Of the study patients, 35 (57.38%) were females, among them 32 were MEN2A. Among 18 index patients 67% were synchronously detected to have MTC and PCC while 33% had MTC preceding PCC. Among patients with MEN2A syndrome 33 (59%) had MTC, 21(38%) had simultaneous PCC and MTC and one patient had PCC as presentation. We noted PHPT in 5 (9%) patients with MEN2A syndrome. Of the 5 patients with MEN2B syndrome, 4 (80%) presented with synchronous MTC and PCC and one (20%) presented with MTC aloneMetastatic MTC was noted in six patients with MEN2A syndrome and two patients with MEN2B syndrome. Median baseline Sr calcitonin level was 42 (4-1721) pg./ml in non-Metastatic group vs 3945(928-35572) pg./ml in distant metastasis group. 1 patient had metastasis from PCC to liver. Mutational analysis data are available for 40 patients. The most common mutations in MEN2A and MEN2B groups were C634R (exon 11 of RET gene, n=21) and M918T (exon 16 of RET gene, n=4), respectively.A total of 177 eligible family members of index patients with MEN2A syndrome were contacted, of whom 83 turned up for screening and 42 (50.6%) had elevated serum calcitonin levels (>10 pg./ml). Of the 26 eligible family members of index patients with MEN2B syndrome, only 9 could be screened and all had normal serum calcitonin levels (<10 pg./ml). Discussion & Conclusion: 1) This is the largest study comprising 61 patients after screening 24 family members in India. 2) Synchronous presentation of MEN2 with PCC and MTC is 67% vs 17% in western literature in Index patients. 3) MEN2 syndrome should be suspected in patients with MTC and young-onset PCC and all first-degree relatives of index patients with this syndrome. Presentation: Saturday, June 17, 2023

Genetic testing and family screening in idiopathic pediatric cardiomyopathy: a prospective observational study from a tertiary care center in North India

IntroductionThere are limited data on family screening and genetic testing in pediatric cardiomyopathy from India. This study was conducted to describe the morphologic spectrum and identify potential familial and genetic causes of pediatric cardiomyopathies in this region.MethodsFrom April 2018 to May 2020, all children from birth to 18 years of age with cardiomyopathy visiting a tertiary care hospital in North India were enrolled in this study. First-degree relatives of index patients were offered screening for cardiomyopathy; 260 clinically reported pathogenic/likely pathogenic variants in 17 genes were analyzed by a rapid genotyping method. Additionally, a subset of patients also underwent whole-exome sequencing.ResultsOf the 20 patients enrolled in this study (median age 42 months), 18 were clinically diagnosed with dilated cardiomyopathy. We observed a 44.4% mortality rate after a median follow-up of 15 months. 61.3% of the eligible first-degree relatives underwent screening, and one patient was identified to have familial cardiomyopathy. Multi-panel gene testing was performed on 18 patients, and none were found to have a pathogenic or likely pathogenic variant; 9 patients also underwent whole-exome sequencing, and pathogenic and likely pathogenic variants were identified in 50% (4/8) of them.ConclusionDilated cardiomyopathy is the most common morphologic form of pediatric cardiomyopathy in India and has a high mortality rate. The prevalence of familial cardiomyopathy was low in this study. Future studies should evaluate the role of whole-exome sequencing in identifying genetic causes of cardiomyopathy in children.

Familial aggregation and heritability of ankylosing spondylitis - a Swedish nested case-control study.

ObjectivesAS is known to be a highly heritable disease, but previous studies on the magnitude of the familial aggregation and heritability of AS have been small and inconclusive, with familial relative risks ranging from 17 to 94. We aimed to improve estimates of these factors by studying families of all subjects diagnosed with AS in Sweden over a period of 16 years and to investigate if familial risks vary by sex or type of relative.MethodsIn a nested case–control study, we identified AS index patients from the National Patient Register (NPR) and the Swedish Rheumatology Quality Register (SRQ) between 2001 and 2016. Each index patient was matched on age and sex to up to 50 general population controls. First-degree relatives of index patients and controls were identified through the Multi-Generation Register, with disease status ascertained in the NPR and SRQ. Familial risks were defined as odds ratios (ORs) of having AS when exposed to a first-degree relative with AS, using conditional logistic regression.ResultsThe overall familial OR for AS was 19.4 (95% CI 18.1, 20.8). Estimates were similar for different relative types and by sex, but having more than one affected relative resulted in a higher risk [OR 68.0 (95% CI 51.3, 90.1)]. Heritability, estimated by assuming sibling risks were completely due to genetics, was 77% (95% CI 73, 80).ConclusionAlthough the familial risk and heritability of AS are higher than for most other diseases, we report estimates that are substantially lower than commonly referenced numbers for AS from other populations.

Lethal privacy: Quantifying life years lost if the right to informational self-determination guides genetic screening for Lynch syndrome

Genetic relatives of hereditary colorectal cancer patients with Lynch syndrome (LS) are at risk of cancer. Testing both colorectal cancer patients and relatives of mutation carriers for LS allows targeted prevention. However, this could mean disclosing sensitive health data to family members. In light of potential trade-offs between cost-effectiveness and patient privacy, this study investigates the implications of increasing test uptake in Germany.Out of 22 screening strategies for LS, the non-dominated and current German strategies were assessed from the perspective of the statutory health insurance. Life years gained by increased prevention were estimated with Markov models. The effects and implications of different test uptake rates in index patients and their relatives were investigated by scenario analysis.Privacy limitations could yield health gains of up to 2500 undiscounted life years for first-degree relatives of index patients and substantially improve cost-effectiveness. However, this approach may contradict the right to informational self-determination.This study demonstrates the effect higher LS test uptakes could have on the lives and rights of colorectal cancer patients and their relatives. It shows potential conflicts between the efficient use of health care resources on the one hand and reasonable consideration of patient autonomy on the other.

Carbamazepine-Induced Stevens–Johnson Syndrome and HLA-B*1502 Screening among First-degree Relatives of Index Patients

Background: Carbamazepine (CBZ) is often implicated in drug-induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). CBZ-induced SJS/TEN is strongly associated with the HLA-B*1502 allele in Southeast Asia. Objectives: The objective was to determine the prevalence of HLA-B*1502 allele in patients with CBZ-induced SJS/TEN and in their first-degree relatives. Materials and Methods: Ten cases of CBZ-induced SJS/TEN from a single center were contacted and offered HLA-B*1502 genotyping for themselves and their first-degree relatives. Eight patients and 12 relatives consented for genotyping. Results: HLA-B *1502 was positive in all patients who were tested, of whom 50% of them were Malay and 50% were Chinese. The frequency of the HLA-B*1502 allele in the first-degree relatives was 58%. Conclusion: HLA-B*1502 is common in first-degree relatives of patients with CBZ-induced SJS/TEN.

Family occurrence of autoimmune hepatitis: A Danish nationwide registry-based cohort study

It is widely believed that autoimmune hepatitis accumulates in families, but the degree of familial clustering has not been clarified. We conducted a population-based study on the family occurrence of autoimmune hepatitis. Through Danish nationwide registries we identified 8,582 first-degree and 9,230 second-degree relatives of index patients diagnosed with autoimmune hepatitis in 1994-2015; and 64 co-twins of index patients diagnosed with autoimmune hepatitis in 1977-2011. For first- and second-degree relatives we calculated the sex- and age-adjusted standardized incidence ratio of autoimmune hepatitis relative to the general population, and we calculated the cumulative risk, i.e. the cumulative incidence, of developing autoimmune hepatitis from the time of the index patient's diagnosis. For co-twins, we estimated the standardized incidence ratio and the concordance rate of autoimmune hepatitis. In first-degree relatives, there were six incident autoimmune hepatitis diagnoses during 64,020 years of follow-up: the standardized incidence ratio was 4.9 (95% CI 1.8-10.7), and the 10-year cumulative risk was 0.10% (95% CI 0.04-0.23). In the second-degree relatives, there were no incident autoimmune hepatitis diagnoses (expected number assuming incidence rate as in the Danish general population = 0.8). In the co-twins, there was one incident autoimmune hepatitis diagnosis during 1,112 years of follow-up, and the standardized incidence ratio was 53.9 (95% CI 1.4-300.4). The probandwise concordance rate, a measure of heritability, was higher in monozygotic than in dizygotic twins (8.7% [95% CI 1.1-28.0] vs. 0%). This nationwide study indicates that only first-degree relatives of index patients with autoimmune hepatitis are at increased risk of autoimmune hepatitis from the time of the index patient's diagnosis, but the absolute risk is very low. Autoimmune hepatitis is a chronic liver disease caused by a dysfunctional immune system. It is widely believed that autoimmune hepatitis accumulates in families. We studied the family members of patients with autoimmune hepatitis from the entire Danish population. We found that autoimmune hepatitis does accumulate in families, but the risk of autoimmune hepatitis in the family members is very low.

Altered DLPFC-Hippocampus Connectivity During Working Memory: Independent Replication and Disorder Specificity of a Putative Genetic Risk Phenotype for Schizophrenia.

Altered connectivity of dorsolateral prefrontal cortex (DLPFC) and hippocampus during working memory is considered an intermediate phenotype for schizophrenia (SCZ), but the relevance for other mental disorders with shared genetic background remains unknown. Here we investigated its presence in unaffected first-degree relatives of patients with bipolar disorder (BD) or major depressive disorder (MDD). Furthermore, we aimed to provide an independent replication of this phenotype in first-degree relatives of SCZ patients. We acquired functional magnetic resonance imaging (fMRI) data from 309 healthy controls and 218 healthy first-degree relatives of index patients with SCZ (n = 62), BD (n = 66) and MDD (n = 90), who completed the n-back working memory paradigm. We observed a significant group effect on DLPFC-hippocampus coupling (PFWE = .031, all P-values region of interest [ROI] corrected). Post hoc comparisons revealed that this effect was driven by the SCZ relatives, who showed a significant increase in the negative functional connectivity of the DLPFC and right hippocampus compared to controls (PFWE = .001), BD relatives (PFWE = .015) and trend-wise also MDD relatives (PFWE = .082). Comparison of BD and MDD relatives to the controls revealed no difference (PFWE-values > .451). Supplementary analyses suggested that the SCZ relatives finding is robust to a range of potential confounds, including structural differences. Our data further support altered DLPFC-hippocampus connectivity during working memory as an intermediate phenotype for SCZ. This suggests that this phenotype is relatively specific to SCZ and does not translate to other genetically related disorders in the mood-psychosis spectrum.

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.

ABSTRACTTransthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, severe, and irreversible, adult‐onset, hereditary disorder caused by autosomal‐dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR‐FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease‐modifying treatment options for a wider spectrum of patients with TTR‐FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation‐specific predictive genetic testing in first‐degree relatives of index patients diagnosed with TTR‐FAP and the structured clinical follow‐up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353–360, 2016

Alopecia Areata: The Role of Stressful Events and an Estimate of Lifetime Risk in First-Degree Relatives

Background: Alopecia areata (AA) is a common disease in the military population; however, a few studies have calculated the lifetime risk of alopecia areata in first-degree relatives of patients as well as the impact of stress. Objectives: The primary aim of this study was to calculate the lifetime risk of alopecia areata in first-degree relatives of index patients. The secondary aim of this study was to assess the role of stressful events in the onset/recurrence of disease. Patients and Methods: One hundred and twenty-one patients with alopecia areata and their first-degree relatives, which included 597 subjects in addition to 119 controls, were studied. We considered a gender and age-matched control for each patient. They were investigated for the occurrence of stressful events within the previous six months before the onset/recurrence of the disease. Results: More than twenty-six percent of patients had a positive family history, while 6.4 percent of first-degree relatives were affected by alopecia areata. Lifetime risks were estimated at 7.6% for parents, 9.9% for siblings, and 6.4% for children. Eighty-eight patients (73.9%) experienced stressful events within six months prior to the onset or recurrences of alopecia areata, while 32 subjects (26.9%) of the control group reported such events in the last six months (P value = 0.000). Conclusions: Calculated lifetime risks can be used in genetic counseling. It appears that stressful events can be considered to be contributing factors in the development of alopecia areata. Also, according to our results, the role of stress in the recurrence of alopecia areata is more prominent than the primary development of the disease.

Risk Factors in Patients with Hereditary Gallstones in Chinese Pedigrees

Objective: We aimed to define the risk factors and to evaluate the impact of family background on the prevalence of gallstones in China. Subjects and Methods: Thirty-eight gallstone pedigrees were collected and a case-control study was conducted. This study consisted of 272 first-degree relatives and 201 non-first-degree relatives of index patients. The participants completed a questionnaire and underwent physical and ultrasonographic examinations. The risk factors examined included age, sex, body mass index (BMI), smoking status, alcohol consumption, pregnancy, fat content in dietary meat, history of gastrointestinal surgery, hypertension, hyperlipidemia, fatty liver, coronary heart disease and diabetes. Results: The prevalence of gallstones in first-degree and non-first-degree relatives of index patients was 38.2 and 10.9%, respectively. Age, pregnancy and BMI significantly differed between cases and controls (p < 0.05). The relative risks were: consumption of meat with a high fat content 1.4 (95% CI 1.1–1.8); hyperlipidemia 2.4 (95% CI 1.3–4.6); diabetes 1.9 (95% CI 1.1–3.2); fatty liver 4.9 (95% CI 1.0–24); coronary heart disease 2.5 (95% CI 1.7–3.9). Conclusion: Data showed that age, overweight, more consumption of high-fat food, high frequency of pregnancy, fatty liver, hyperlipidemia, coronary heart disease and diabetes could increase the risk of gallstones in the first-degree relatives of index patients.

Familal left ventricular hypertrabeculation (noncompaction) is myopathic

BackgroundLeft-ventricular hypertrabeculation/noncompaction(LVHT) is a cardiac abnormality of unknown aetiology, frequently associated with arrhythmias, heart failure, and embolism. In most cases LVHT is associated with neuromuscular disorders (NMDs) or other rare non-neuromuscular genetic syndromes. Occasionally, LVHT occurs familiarly. Methods and resultsInvited for a cardiologic investigation were all first-degree relatives of index patients with LVHT who attended the cardiologic department. Altogether 25 relatives of 15 index patients from 15 families were investigated. Three members each were investigated in 3 families, 2 patients each in 4 families and 1 member each in 8 families. Among the 25 relatives from the 15 families, LVHT was found in 4 of them. Accordingly, familial LVHT was detected in 4 of the 15 investigated families (27%). Among the 4 relatives with LVHT, extension and morphology were similar to the appropriate index patient in 2 families. A NMD was diagnosed in three of the four relatives (75%) with familial LVHT. One relative without LVHT presented with a history of Fallot's tetralogy, and two relatives each presented with thickening of the left-ventricular myocardium. ConclusionsLVHT is familial in at least 27% of the patients with LVHT. LVHT may differ between relatives in some of the patients with familial LVHT. Familial LVHT is associated with a NMD in the majority of the cases. Relatives of LVHT patients may present with cardiac abnormalities other than LVHT.

Increased Cancer Predisposition in Family Members of Colorectal Cancer Patients Harboring the p.V600E BRAF Mutation: a Population-Based Study

The serrated pathway represents a distinct molecular pathway of colorectal carcinogenesis and is associated with the p.V600E BRAF mutation. The objective of this study is to characterize the cancer family history and clinicopathologic features of colorectal cancer (CRC) patients according to the microsatellite instability (MSI) and BRAF mutation status of their tumors. The tumors from 558 population-based CRC patients underwent pathologic examination and molecular analysis for MSI, BRAF, and germline mutations in mismatch repair genes MUTYH and APC. The cancer history in first-degree relatives (FDR) of index patients was ascertained. The risk of CRC in FDRs of index patients with MSI-H BRAF mutation [hazard ratio (HR) = 2.49; 95% confidence interval (95% CI), 1.57- 3.93] and microsatellite-stable BRAF mutation tumors (HR = 1.64; 95% CI, 1.01-2.66) was significantly elevated compared with FDRs of index patients with microsatellite-stable BRAF wild-type tumors. The incidence of nonmelanoma skin cancer was also significantly elevated in FDRs of patients with BRAF mutation CRC (HR = 2.52; 95% CI, 1.31-4.86). Furthermore, BRAF mutation CRC was associated with a distinct clinical, molecular, and pathologic phenotype. The increased incidence of cancer in FDRs of index CRC patients with the p.V600E BRAF mutation may be explained by a genetic predisposition to develop cancer through the serrated pathway of colorectal carcinogenesis. Family members of BRAF CRC patients have an increased predisposition to develop cancer. Future work should aim to identify the causative genetic factors.

Diagnosis of Familial Hypercholesterolemia in General Practice Using Clinical Diagnostic Criteria or Genetic Testing as Part of Cascade Genetic Screening

Background: Too few familial hypercholesterolemia (FH) patients are diagnosed. The most cost-effective strategy to diagnose FH is to examine first-degree relatives of already diagnosed patients. This is referred to as cascade genetic screening. Methods and Results: One thousand eight hundred and five first-degree relatives of index patients with molecularly defined FH consented to cascade genetic screening by the use of molecular genetic testing. Of these, 44.8% were mutation carriers and 55.2% were noncarriers. Only 44.2% of the mutation carriers were on lipid-lowering drugs at the time of genetic testing. Of these, only 9.4% had a value for total serum cholesterol below 5 mM. Among adult mutation carriers who were not on lipid-lowering treatment at the time of genetic testing, reductions in total serum cholesterol and low-density lipoprotein cholesterol of 18.4% (p < 0.0001) and 25.3% (p < 0.0001), respectively, were observed 6 months after genetic testing. It is assumed that this improvement in the lipid profile is due to a definite diagnosis obtained by molecular genetic testing. By using the results of genetic testing as the gold standard for diagnosis of FH, data from a questionnaire filled out by the relatives showed that the use of clinical criteria to diagnose FH in general practice had a sensitivity of 46.2% and a specificity of 88.0%. Conclusions: The use of clinical diagnostic criteria to diagnose FH in general practice identifies only approximately 50% of FH patients. Molecular genetic testing as part of cascade genetic screening is an efficient tool to diagnose patients, leading to significant improvement in the lipid profile. It should therefore be implemented in clinical medicine.

Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): A study of 130 kindreds in the United Kingdom

To estimate the relative risks of cancer in first-degree relatives of index patients, 130 pedigrees of dominantly inherited Lynch type II cancer family syndrome have been analysed. The risk of death from all causes was significantly increased in women over 45 years of age and the overall liability to cancer in women was greater than for men. A sevenfold increase in risk of colon cancer was found in both sexes. In female relatives the risk of breast cancer was increased fivefold and lifetime risk of breast cancer was 1 in 3.7. A screening programme based on estimated risks could be offered to first-degree relatives of index patients with Lynch type II cancer family syndrome.

Risk of obstetric cholestasis in sisters of index patients.

The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care.

Abstracts of literature

Abstracts of literature

Demographic and Clinical Features of Diabetes Mellitus in 1095 Yemeni Patients

The ever-increasing incidence of diabetes mellitus is a cause for growing public health concern in both developed and developing countries. In this study, we aim to explore the special demographic and clinical features of diabetes, as seen in a large sample of Yemeni patients, and to compare these features with those reported in other countries. All patients referred to our diabetic clinic over a five-year period were investigated according to a standardized protocol. Data was collected and fed into a personal computer with a software statistical package for analysis. The relative frequencies of clinical classes of diabetes were 10.5% for IDD, 58.6% for non-obese NIDDM; 26.2% for obese NIDDM, and 4.7% for IGT. In the IDDM class, the age-specific relative frequency rate showed a higher and earlier onset peak frequency in females than in males. Among NIDDM class, about 31% of patients were diagnosed under the age of 45 years, and only 12% were first diagnosed after the age of 65 years. Most NIDDM patients came from social classes I and II (professionals and intermediate professionals) and most IDDM patients came from social class IIIM (skilled manual). A positive family history of diabetes among first-degree relatives of index patients was observed in 33.7% of IDDM patients, in 30% of non-obese NIDDM patients, in 39.2% of obese NIDDM patients and 32% of IGT patients. Female NIDDM patients had a significantly higher mean body mass index (BMI) than males (P<0.0001). Hypertension was recognized in 24.2% of the diabetic population aged 20 to A(3) 65 years. Large vessel disease (LVD) was observed in 28% of patients, small vessel disease (SVD) in 45%, and peripheral neuropathy in 40.7%. Inadequate glycemic control was noticed during follow-up in the majority of patients. Diabetes mellitus in Yemen, especially NIDDM, is characterized by an earlier age at onset, and predominance of males and non-obese NIDM subclass. Other characteristics include moderate genetic susceptibility, inadequate glycemic control and high prevalence of chronic complications.

High familial prevalence of gallstones in the first-degree relatives of gallstone patients

Limited information is available on the prevalence of gallstones in the first-degree relatives of gallstone patients. Three groups of subjects were studied by real-time ultrasound examination: group A, 105 index gallstone patients (male/female; 20:85); group B, 330 first-degree relatives of index patients; group C, matched controls for group A (n = 105) and group B (n = 330) subjects. Dietary, anthropometric, and biochemical investigations were carried out. In 39 of 105 (37%) index cases, one or more additional family members had gallstones (positive-index case). The positive-index cases were younger than the remaining index cases (mean age, 33.1 +/- 14 vs. 44.5 +/- 13.1 years; P < .05). Fifty-one of 330 (15.5%) first-degree relatives had gallstones, nearly four and a half times (95% confidence interval [CI], 2.4 to 8.5) more often than in the matched control population (12 of 330 [3.6%]). Thirty-three of 51 (65%) positive relatives were women; mother (37.3%), sister (17.6%) or daughters (10%) to the index patients. There was no difference in the diet, physical activity, and serum lipid profile between the positive index patients and the remaining gallstone patients and positive relatives and their controls. Our results show that there is a strong familial predisposition for gallstone formation. Female relatives of young gallstone patients should be routinely screened for gallstones.

High familial prevalence of gallstones in the first-degree relatives of gallstone patients

Limited information is available on the prevalence of gallstones in the first-degree relatives of gallstone patients. Three groups of subjects were studied by realtime ultrasound examination: group A, 105 index gallstone patients (male/female; 20:85); group B, 330 first-degree relatives of index patients; group C, matched controls for group A (n = 105) and group B (n = 330) subjects. Dietary, anthropometric, and biochemical investigations were carried out. In 39 of 105 (37%) index cases, one or more additional family members had gallstones (positive-index case). The positive-index cases were younger than the remaining index cases (mean age, 33.1 ± 14 vs. 44.5 ± 13.1 years; P < .05). Fifty-one of 330 (15.5%) first-degree relatives had gallstones, nearly four and a half times (95% confidence interval [ci], 2.4 to 8.5) more often than in the matched control population (12 of 330 [3.6%]). Thirty-three of 51 (65%) positive relatives were women; mother (37.3%), sister (17.6%) or daughters (10%) to the index patients. There was no difference in the diet, physical activity, and serum lipid profile between the positive index patients and the remaining gallstone patients and positive relatives and their controls. Our results show that there is a strong familial predisposition for gallstone formation. Female relatives of young gallstone patients should be routinely screened for gallstones.

Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease

For each of 41 index patients with probable Alzheimer's disease and a first episode of major depression and 71 nondepressed Alzheimer's disease patients, two first-degree relatives were interviewed by a rater blind to presence or absence of depression in the proband. The depressed patients had significantly more first- and second-degree relatives with depression than did control subjects. The lifetime risk for major depression, adjusted for differences in age distribution, was significantly greater in first-degree relatives of index patients, suggesting that depression in Alzheimer's disease is genetically related to primary affective disorder. Alzheimer's disease may be useful for studying aspects of depressive pathophysiology.