Familial chondrocalcinosis

The first-degree consanguineous relatives of 46 patients with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease were examined for the presence of articular chondrocalcinosis. In 5 cases the process was familial, with 17 persons in the oldest living generation (mean age 69 ± 7.4) showing radiographic evidence of calcified cartilage. The clinical syndrome was characterized by a female predominance, late onset of symptoms with mild arthritic manifestations, and oligoarticular chondrocalcinosis. These data suggest that the familial type of CPPD crystal deposition disease is more frequent than formerly thought.     

Familial chondrocalcinosis in the Spanish population

We have found in our clinic a 28.1% prevalence of familial chondrocalcinosis among 149 family members of 32 patients with calcium pyrophosphate dihydrate deposition disease. The clinical and radiological characteristics of these familial chondrocalcinosis patients were similar to those of the Chiloes with familial chondrocalcinosis previously reported. No significant clinical or radiological differences were detected between our sporadic and familial chondrocalcinosis patients. Our findings support the hypothesis that the Chiloes familial chondrocalcinosis was carried to Chile by Spanish immigrants.     

Hereditary articular chondrocalcinosis. Clinical and genetic features in 13 pedigrees

Thirteen pedigrees with familial articular chondrocalcinosis were identified through a systematic radiologic survey of the first-degree blood relatives of 76 patients with chondrocalcinosis. Forty-one persons, 30 women and 11 men, distributed in 25 sibships were affected. Their mean age at the time of study was 65.09 +/- 11.36 years. The disease was of early onset only in four pedigrees. The clinical manifestations in these four pedigrees were similar to those found in the kindred with a late onset. In 15 persons, the process was asymptomatic. In the 26 symptomatic patients, the arthropathy was mild, with clinical and radiologic features similar to those observed in sporadic chondrocalcinosis. There was no linkage of chondrocalcinosis to the HLA-A and HLA-B antigens in the 11 pedigrees in which tissue typing was performed. The pattern of involvement in these 13 pedigrees supports an autosomal dominant mode of inheritance. These data suggest that hereditary chondrocalcinosis is not infrequent and very often is clinically indistinguishable from the sporadic form of the disease.     

Prevalence of inflammatory bowel disease among relatives of patients with Crohn's disease

The prevalence of familial inflammatory bowel disease was 13.4% in a population-based study of 1048 patients with Crohn's disease (CD). Seventy-two of the index cases had 82 first-degree relatives. Forty-nine were more distantly related (19 first cousins from the same generation as the index patient). The prevalence of CD among first-degree relatives was 21 times higher than among non-relatives. Four of six monozygotic twins were concordant. The age at onset was 25 years in the patients with familial CD, compared with 33 years in the entire group. An additional 53 relatives were found to have ulcerative colitis (UC). The prevalence of UC among first-degree relatives of patients with CD was six times higher than among non-relatives.     

Chondrocalcinosis and hypomagnesemia: clinical and radiological progression

Hypomagnesemia is a rare secundary metabolic disorder associated with calcium pyrophosphate dihydrate cristal deposition disease in joint structures and may cause asymptomatic chondrocalcinosis (linear calcification of cartilage), pseudogout, and chronic arthropathy. We report 2 young men with relapsing acute knee monoarthritis with chondrocalcinosis and hypomagnesemia. After follow-up clinical and radiological events al least for 5 years and treatment with magnesium lactate, these patients have not shown new pseudogout attacks. We discuss knee radiological evolution in both patients, outstanding major knee radiological deterioration in the patient with early symptoms and a familial chondrocalcinosis association, in spite of clinical asymptomatic status.     

Familial rheumatoid arthritis in patients referred to rheumatology clinics of Tabriz, Iran

Background: The familial clustering of rheumatoid arthritis (RA) in first and second degree relatives of patients supports the role of genetic factors. The proportion of heredity in its development is roughly 60%; however, most individuals closely related to someone with RA do not get the disease. Considering the lack of sufficient data on the familial aggregation of RA in Iran, we designed this study for clarifying the familial prevalence of RA. Objective: To determine the prevalence of RA among relatives of patients with RA and to evaluate the mean disease onset age in relatives. Methods: In a longitudinal study from July 2008 to July 2010, we followed 210 unrelated patients with RA and their first and second degree relatives (FDR+ and SDR+), by interviewing and physical examination of those with symptoms, to ascertain prevalence. Familial RA was defined by presence of at least two siblings fulfilling the 1987 ACR criteria for RA. Results: We demonstrated that 17.6% of patients have at least one affected relative. The prevalence of RA in the family of studied patients was 0.83% (42 people). Thirty‐two in FDR+ and 10 people in SDR+ (2.53% and 0.26% of all family), also 1.12% in female relatives and 0.39% in male relatives had RA. The odds ratio for FDR/SDR was 2.52. The mean age at disease onset in relatives was 42.30 ± 1.51 years in FDR+ and 34.40 ± 2.10 years in the SDR+ group (0.03). Conclusion: The risk of RA is greatest in FDR+ and is likely to be due to a combination of inherited and environmental factors.     

Prevalence of articular chondrocalcinosis in elderly subjects in a rural area of Catalonia.

OBJECTIVES--To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis in the elderly population of Osona, a rural area of Catalonia, north east Spain. METHODS--Knee and wrist radiographs were performed on 261 subjects (141 women, 120 men) aged at least 60 years, who attended a series of 35 general practitioners for various medical problems. RESULTS--Twenty seven subjects had articular chondrocalcinosis, which represents a crude prevalence of 10%. Articular chondrocalcinosis was more often observed in women than in men (14 v 6%). Articular chondrocalcinosis increases in occurrence with age, rising from 7% in subjects aged 60-69 years to 43% in subjects older than 80 years. A similar occurrence of articular chondrocalcinosis was noted in the indigenous population, in which several cases of familial chondrocalcinosis have previously been reported, and in subjects born in other areas of Spain. All but one subject with articular chondrocalcinosis had chondrocalcinosis of the knee. The occurrence of rheumatic disorders did not differ significantly between subjects with articular chondrocalcinosis and those without. CONCLUSIONS--Articular chondrocalcinosis is an age related disorder, which could partly explain the discrepancies in its prevalence reported in previous studies. In most subjects with articular chondrocalcinosis recruited from an unselected population the clinical manifestations are probably mild or even absent.     

Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics.

AIMS: To assess the prevalence of familial non-X-linked dilated cardiomyopathy, to diagnose early asymptomatic cases evaluate inheritance and characterize clinical phenotypes. METHODS AND RESULTS: We screened 472 relatives of 104 consecutive patients diagnosed with dilated cardiomyopathy; males with X-linked dilated cardiomyopathy were excluded based on systematic immunohistochemical and molecular analysis. Relatives underwent clinical examination, electrocardiography, echocardiography and serum creatine-phosphokinase determination. Twenty-six index patients (25%) had familial disease: four youths (< or = 20 years) had rapidly progressive outcome and underwent emergency transplantation. In a sib-pair, the onset was with atrioventricular block. Inheritance was autosomal dominant in 15, undetermined in seven (four sib-pairs); mitochondrial DNA pathological mutations were found in four. The screening identified 23 newly diagnosed relatives in the familial group. Transplantation (P = 0.04) and atrial fibrillation (P = 0.04) were more frequent, and left bundle branch block (P = 0.04) less frequent in index patients with familial than in those with non-familial disease. Several non-affected relatives had instrumental abnormalities potentially useful as pre-clinical markers: their prevalence was similar in both groups. CONCLUSIONS: The prevalence of familial, non X-linked dilated cardiomyopathy was 25%. The immediate benefits of screening family members of index patients was early diagnosis in unaware symptomless affected relatives.     

Families at risk of colorectal cancer: who are they?

The first degree kinships of 305 index cases have been studied to determine whether an early age of onset or a particular site distribution characterizes familial aggregations of colorectal cancer. The probands comprised 100 patients aged 55-74 years and 205 patients under 55 years at diagnosis and were drawn from a large population database. Ascertainment and verification were complete for 2566 of 2657 first degree relatives. The history of cancer in 296 relatives was validated in 96% of cases from medical or other records. Among kinships ascertained through index cases under 55 years of age, less than 5% had three or more individuals affected by colorectal cancer. The comparable proportion of older probands' families was 3%. Probands with proximal disease were no more likely to have a positive family history of bowel cancer than those with disease distal to the splenic flexure. These findings are consistent with other population based studies of the epidemiology of familial colorectal cancer but contrast with reviews from referral centres and family cancer clinics.     

Ankylosing spondylitis: interaction between genes, joints, age at onset, and disease expression.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disorder with symptom onset generally occurring in the late teens/mid-twenties. In women, a younger age at onset enhances disease susceptibility in the next generation. We examined the influence of age at symptom onset on phenotypic expression. METHODS: Patients were divided into cohorts according to age of symptom onset. The primary outcome measure was radiological progression (by Bath AS Radiology Index, BASRI). Secondary measures were disease activity (Bath AS Disease Activity Index, BASDAI), function (Bath AS Functional Index, BASFI), numbers undergoing AS related surgery, and percentage with secondary disorders. RESULTS: Age at onset had no significant effect on radiological progression (young onset vs late onset, 8.0, 8.6, respectively) disease activity (young vs late, 4.4, 4.4), need for non-hip surgical intervention (9%, 8%, respectively), or prevalence of secondary disorders (iritis, 40%, 41%; psoriasis, 20%, 19%; inflammatory bowel disease, 7.5%, 8.9%). By contrast, there was a striking increase in prevalence of total hip replacement in those with juvenile onset (18%, 8%, respectively; p < 0.001). Regardless of age at onset, spinal progression determined radiologically was greater in those with hip arthritis compared to those without (young onset hip involvement vs non-hip involvement, 9.7 (2.4), 7.2 (3.0) (p < 0.001); late onset hip involvement vs non-hip involvement, 10.1 (2.5), 7.1 (3.0), respectively]. Function deteriorates with age (young onset vs late onset, 3.7, 4.5, respectively; p < 0.01). CONCLUSION: (1) Hip disease (young or late onset) is a major prognostic marker for longterm severe disease (patients with hip disease have a spinal score increased by 2.5-3 points or 35-40% more change). (2) Hip involvement is more prevalent among patients with young age at onset. (3) Young onset patients without hip involvement do not have more severe disease. Thus, age at onset, itself, does not influence disease severity. (4) Since hip involvement and not age at onset is associated with worse outcome, patients with a young age at onset may be assumed to have an increased susceptibility load (i.e., genetic component or environmental trigger) rather than more severity genes. The lack of association between severity and age at onset implies that the determinants of susceptibility and severity are independent.     

Calcium pyrophosphatase dihydrate (CPPD) crystal deposition disease in a teaching hospital in Kuwait

OBJECTIVE: A Medline electronic search showed a paucity of reports on calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) from the Gulf region. To date only a single case report has been published from this region. Therefore, this study aimed, firstly, at finding out the prevalence of chondrocalcinosis in adult Arabs in Kuwait presenting with knee arthritis and, secondly, at carrying out an observational study of CPPD-CDD among Arabs in Kuwait. METHODS: For the study of the prevalence of chondrocalcinosis 100 consecutive adult patients presenting with knee arthritis were radiologically examined. For the observational study the clinical, laboratory, and radiological findings were analysed in patients with CPPD-CDD seen over a period of five years. RESULTS: This study showed the presence of chondrocalcinosis in two (2%) of the 100 adult Kuwaiti and other Middle-Eastern Arab patients (70 men, 30 women, median age 50 (range 45-80)) who presented to the rheumatology clinic for the evaluation of knee pain. When the younger age of the group (only three patients aged >70) is taken into account the figure was comparable with that reported from Western countries. Over a period of five years a total of 2726 new patients were evaluated at the rheumatology clinic of this institution. A diagnosis of crystal arthritis was made in 85 patients (3%). Fourteen of these 85 (that is, 16.5%, but 0.5% of the total cases) were diagnosed with definite (eight patients) or probable (six patients) CPPD-CDD. Different clinical presentations, including that of acute monarthritis (that is, pseudogout), premature generalised osteoarthritis, and polyarticular rheumatoid-like presentations, were seen in different patients. Overlap with true gout, with the additional presence of monosodium urate crystals in the joint aspirate, was seen in two patients. CONCLUSION: The present report shows that CPPD-CDD may not be uncommon among Arabs in the Gulf region. A high degree of clinical awareness and routine examination of joint aspirates with careful analysis for crystals may make it a more common diagnosis in this part of the world. In this regard it is interesting to note that cases and case series including familial cases have been reported from North Africa, especially Tunisia, indicating that the disease has been well described in Arabs of other geographical regions.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

Clinical heterogeneity of familial colorectal cancer and its influence on screening protocols.

The age at onset of non-polyposis colorectal cancer (CRC) was investigated in 49 families with at least three relatives affected in two successive generations. Forty one of these families satisfy the accepted minimum criteria for hereditary non-polyposis CRC. The remaining eight families were distinguished by a late age of disease onset and, hence, could not be included in the group. The condition in these latter families has been designated provisionally, as late onset familial CRC. The hereditary non-polyposis CRC families include 194 patients, 110 men and 84 women (mean age at diagnosis: 44 years; range: 16-74 years). Ninety two per cent of the patients were diagnosed by age 60. Colorectal cancer was diagnosed at progressively earlier ages in successive generations (p < 0.0005). The late onset CRC families comprised 30 patients, 20 men and 10 women (mean age at diagnosis: 62 years; range: 51-77 years). Fifty eight per cent of the CRCs in the patients belonging to the hereditary non-polyposis CRC families were located in the right colon compared with 13% in the late onset familial CRC group (p < 0.001). Multiple CRCs were found in 23% of the cases in the former but in only 3% in the latter families (p < 0.05). Adenomas associated with CRC were reported in 14.5% of the cases in the hereditary non-polyposis CRC families and in 30% of the cases in the late onset familial CRC group (p = NS). Extracolonic cancers, frequently encountered in hereditary non-polyposis CRC, were not found in the late onset CRC families. These findings indicate that there is a distinct clinical entity of non-polyposis CRC in which colorectal cancer develops at a more advanced age than in hereditary non-polyposis CRC. Future molecular genetic studies should confirm this hypothesis. In the meantime, recognition of these late onset familial CRC families, which will rest on clinical observations, is important because of the implications for the screening protocol.     

Lack of association between hypothyroidism and chondrocalcinosis

The association between hypothyroidism and calcium pyrophosphate dihydrate deposition disease (CPPD) is controversial. We studied the prevalence of chondrocalcinosis, the roentgenographic marker of CPPD by obtaining anteroposterior knee roentgenograms in 49 hypothyroid patients over the age of 40 years, and compared them with knee roentgenograms in 31 euthyroid patients matched for age and sex. Only 2 hypothyroid patients and one euthyroid control had knee chondrocalcinosis. Our results indicate that hypothyroid patients have no greater prevalence of chondrocalcinosis compared to euthyroid subjects. There are also no difference in the degree and prevalence of osteoarthritis between the 2 groups, although hypothyroid patients may have a higher prevalence of periarticular osteopenia.     

Prevalence of inflammatory bowel disease among relatives of patients with ulcerative colitis

The familial occurrence of inflammatory bowel disease (IBD) was investigated among 963 patients with ulcerative colitis (UC) diagnosed in 1955-1979 in Stockholm County. For 76 patients who had a relative with IBD a pedigree was drawn. The diagnoses of the diseased relatives were verified. There was a general prevalence of 7.9% for IBD among relatives. In 80% one relative was affected, in most cases a first-degree relative with UC. Sibship was the commonest relationship. No concordance for UC was found among three pairs of monozygotic twins. The prevalence of UC in first-degree relatives was 15 times higher than in non-relatives. The age of onset was significantly lower among patients with a family history for UC; they also had a higher incidence of total colitis. The prevalence of Crohn's disease in first-degree relatives of patients with UC was almost 3.5 times higher than in non-relatives.     

Familial occurrence of complement dysfunction in Crohn's disease: correlation with intestinal symptoms and hypercatabolism of complement.

Complement was studied in Crohn's disease probands with early onset and in their first degree relatives. Controls included 24 healthy volunteers and 24 patients with ulcerative colitis or peptic ulcers. Subnormal generation of chemotactic activity by the alternative pathway was shown in eight of 21 probands and in six of 33 relatives, a frequency in both groups significantly different from controls (p less than 0.005), with a strong connection between findings in patients and relatives. As previously shown in patients with Crohn's disease, the subnormal generation was related to decreased utilisation of complement C3 in relatives. Raised levels of circulating complement C3c split products suggested complement involvement in Crohn's disease probands. In contrast, plasma C3c was normal in all relatives, and none of the six cases with complement dysfunction had gastrointestinal symptoms or a history of inflammatory bowel disease. Our data suggest, that complement abnormality seen in Crohn's disease patients does not simply reflect mucosal inflammation or hypercatabolism of complement.     

Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort

OBJECTIVE: To determine whether there is familial aggregation of systemic lupus erythematosus (SLE) and/or other autoimmune diseases in SLE patients and to identify clinical differences between patients with and those without familial autoimmunity. METHODS: We interviewed members of the Grupo Latinoamericano de Estudio del Lupus Eritematoso (GLADEL) inception cohort of 1,214 SLE patients to ascertain whether they had relatives with SLE and/or other autoimmune diseases. Identified relatives were studied. Familial aggregation was tested using reported highest and intermediate population prevalence data for SLE, rheumatoid arthritis (RA), or all autoimmune diseases, and studies were performed to identify the genetic model applicable for SLE. RESULTS: We identified 116 first-, second-, or third-degree relatives with SLE, 79 with RA, 23 with autoimmune thyroiditis, 3 with scleroderma, 1 with polymyositis, and 16 with other autoimmune diseases, related to 166 of the 1,177 SLE patients in the GLADEL cohort who agreed to participate. Forty-two SLE patients had 2 or more relatives with an autoimmune disease. We found a lambda(sibling) of 5.8 and 29.0 for SLE and of 3.2-5.3 for RA, when comparing with their reported high or intermediate population prevalence, respectively. We also found familial aggregation for autoimmune disease in general (lambda(sibling) = 1.5) and determined that for SLE, a polygenic additive genetic model, rather than a multiplicative one, is applicable. CONCLUSION: In SLE there is familial aggregation of SLE, RA, and autoimmune disease in general. A polygenic additive model applies for SLE. American Indian-white Mestizo SLE patients and those with higher socioeconomic level were more likely to have familial autoimmunity.     

5例炎症性肠病患者的家系调查及其与遗传易感关系分析

目的 探讨我国炎症性肠病患者的遗传易感倾向.方法 在广泛进行流行病学调查的基础上,采用系谱分析方法,对5例具有家族聚集现象的炎症性肠病患者家系进行病史、临床表现、X线、结肠镜及病理组织学检查、治疗状况、家族成员死亡原因、有无近亲结婚史等的详细调查.结果 2个克罗恩病家族分别有兄弟、母子患病;3个溃疡性结肠炎家族分别有姐弟、母子和祖孙三人患病.患者的一级亲属更易受累,同胞受累最多见,其特点是发病年龄较早、后代发病年龄早且病情重.男女均可发病,患病类型相同,病变部位相似.结论 该调查中的炎症性肠病患者存在着遗传易感倾向,发病人数少,推测可能为多基因遗传或常染色体隐性遗传.     

Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews.

The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non-Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models.     

Prospective evaluation of relatives for familial arrhythmogenic right ventricular cardiomyopathy/dysplasia reveals a need to broaden diagnostic criteria

OBJECTIVES: We sought to ascertain the prevalence and mode of expression of familial disease in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). BACKGROUND: Autosomal-dominant inheritance is recognized in ARVC. The prevalence and mode of expression of familial disease in consecutive, unselected families is uncertain. METHODS: First- and second-degree relatives of 67 ARVC index patients underwent cardiac evaluation with history and examination, 12-lead and signal-averaged electrocardiogram (ECG), two-dimensional and Doppler echocardiography, metabolic exercise testing and Holter monitoring. Diagnoses were made in accordance with published criteria. RESULTS: Of 298 relatives, 29 (10%; mean age 37.4 +/- 16.4 years) had ARVC. These were from 19 of the 67 families, representing familial involvement in 28%. Of these affected relatives, 72% were asymptomatic, 17% had ventricular tachycardia (sustained VT 10%, nonsustained VT 7%) and 21% had left ventricular involvement. A further 32 relatives (11%; 37.7 +/- 12.4 years) exhibited nondiagnostic ECG, echocardiographic or Holter abnormalities. Fifteen of these relatives were from families with only the proband affected, and inclusion of this subset of relatives would have resulted in familial ARVC in 48% of index cases. Four additional relatives (1% to 3%) fulfilled diagnostic criteria for dilated cardiomyopathy without any features of right ventricular disease. CONCLUSIONS: By using current diagnostic criteria, familial disease was present in 28% of index patients. A further 11% of their relatives had minor cardiac abnormalities, which, in the context of a disease whose mode of inheritance is autosomal dominant, are likely to represent early or mild disease expression. We advocate that the current ARVC diagnostic criteria are modified to reflect the broader spectrum of disease that is observed in family members.