Validity of family history data on primary adult-onset dystonia

BACKGROUND: To our knowledge, no study has assessed the validity of family history data provided by probands with adult-onset dystonia. OBJECTIVE: To measure the sensitivity and specificity of interviewing patients with primary adult-onset dystonia as a method for obtaining information on dystonia in first-degree relatives. PARTICIPANTS: Seventy probands with primary adult-onset dystonia were asked to identify first-degree relatives who had dystonia. Available relatives were then directly examined by a trained neurologist. The validity of the probands' reports was tested against the neurologists' diagnoses. RESULTS: Among 300 first-degree relatives who were examined, 26 received a diagnosis of dystonia. Only 7 of the 26 were identified by the probands' reports. Among the 274 relatives free of dystonia, the probands reported 5 as having dystonia. The probands' reports therefore yielded a sensitivity of 27.0% and a specificity of 98.2%. CONCLUSIONS: Because the family history method yields low sensitivity and incurs a risk of misclassification, it is of limited use in family studies of adult-onset dystonia. The only valid means of ascertaining dystonia among relatives remains neurological examination of at-risk subjects.     

Essential tremor centralized brain repository: diagnostic validity and clinical characteristics of a highly selected group of essential tremor cases.

We studied essential tremor (ET) cases enrolled in the Essential Tremor Centralized Brain Repository to (1) assess the validity of their diagnoses and (2) characterize the clinical features in a group of highly selected cases who might reflect a far end of the disease spectrum. Our over-arching goal was to provide a perspective of ET that complements that derived from population-based and clinic-based studies. Based on a history and videotaped examination, 94 of 100 ET cases had their diagnoses confirmed; most of the remainder had Parkinson's disease. When compared with ET cases ascertained through populations and clinics, a large proportion had been prescribed medication for tremor (87.2%), had a family history of tremor (88.3%), had rest tremor (33.0%), or had neck tremor (60.6%). One patient had facial tremor, which has not been reported previously. As has been reported once before, a large proportion wore hearing aids (26.9% of the 67 participants age>or=70). In summary, diagnostic validity was high. In terms of their clinical characteristics, the high proportion of cases with severe tremor and varied disease manifestations (neck tremor, rest tremor) make these cases a valuable resource in pathological studies; the high proportion with familial tremor would provide an enriched sample for genetic studies.     

Validity of family history in essential tremor

In this study, we found the sensitivity and specificity of family history data given by essential tremor (ET) patients to be 43.3% and 94.4%. Compared to relatives with less severe tremor (tremor score <24), those with more severe tremor (tremor score 24) were more likely to be identified by the ET probands (8/8 vs. 5/22, p=0.001, chi2 14.3). Our study suggests that family history information reported by ET patients was inaccurate, and poorly validated. Clinical and genetic studies in ET should take the limitation of family history data into consideration.     

Family history of suicidal behavior and mood disorders in probands with mood disorders

OBJECTIVE: First-degree relatives of persons with mood disorder who attempt suicide are at greater risk for mood disorders and attempted or completed suicide. This study examined the shared and distinctive factors associated with familial mood disorders and familial suicidal behavior. METHOD: First-degree relatives' history of DSM-IV-defined mood disorder and suicidal behavior was recorded for 457 mood disorder probands, of whom 81% were inpatients and 62% were female. Probands' lifetime severity of aggression and impulsivity were rated, and probands' reports of childhood physical or sexual abuse, suicide attempts, and age at onset of mood disorder were recorded. Univariate and multivariate analyses were carried out to identify predictors of suicidal acts in first-degree relatives. RESULTS: A total of 23.2% of the probands with mood disorder who had attempted suicide had a first-degree relative with a history of suicidal behavior, compared with 13.2% of the probands with mood disorder who had not attempted suicide (odds ratio=1.99, 95% CI=1.21-3.26). Thirty percent (30.8%) of the first-degree relatives with a diagnosis of mood disorder also manifested suicidal behavior, compared with 6.6% of the first-degree relatives with no mood disorder diagnosis (odds ratio=6.25, 95% CI=3.44-11.35). Probands with and without a history of suicide attempts did not differ in the incidence of mood disorder in first-degree relatives (50.6% versus 48.1%). Rates of reported childhood abuse and severity of lifetime aggression were higher in probands with a family history of suicidal behavior. Earlier age at onset of mood disorder in probands was associated with greater lifetime severity of aggression and higher rates of reported childhood abuse, mood disorder in first-degree relatives, and suicidal behavior in first-degree relatives. CONCLUSIONS: Risk for suicidal behavior in families of probands with mood disorders appears related to early onset of mood disorders, aggressive/impulsive traits, and reported childhood abuse in probands. Studies of such clinical features in at-risk relatives are under way to determine the relative transmission of these clinical features.     

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.     

Subclinical tremor in normal controls with versus without a family history of essential tremor: data from the United States and Turkey

Background and purpose: Mild action tremor is very common in the population. One fundamental question is whether this tremor is related to the neurological disease essential tremor (ET), which occurs in a much smaller segment of the population? ET is often genetic, and variable phenotypic expression is well‐documented in the literature. We determined whether normal controls who report a family history of ET have greater action tremor than normal controls who do not report such a history. Methods: Controls, enrolled in two epidemiological studies (New York and Turkey), were examined in detail and action tremor was rated using a valid and reliable clinical rating scale, resulting in a total tremor score (range 0–36). Results: In New York, the total tremor score was higher in 44/406 (10.8%) controls who reported a family history of ET than in 362/406 controls with no such history (4.25 ± 2.51 vs. 3.78 ± 2.93, P = 0.02). Controls who reported a first‐degree relative with ET had the highest total tremor scores. In Turkey, the total tremor score was higher in 7/89 (7.9%) controls with a family history than in 82/89 controls with no family history (3.43 ± 4.54 vs. 1.13 ± 2.54, P = 0.048). All affected relatives in Turkey were first‐degree. Conclusions: These data suggest that some of the normal tremor exhibited by people in the population is likely to be subclinical, partially expressed ET and that the sphere of ET is wider than is apparent from a consideration of clinically diagnosed cases.     

Familial associations of Alzheimer disease and essential tremor with Parkinson disease

Background: We constructed a cohort of first‐degree relatives of participants in a population‐based case–control study of Parkinson disease (PD) and compared the occurrence of Alzheimer disease (AD) and essential tremor (ET) in relatives of PD cases and controls. Methods: We relied on proband interviews to assess family history in 372 probands with incident PD confirmed by a movement disorder specialist and 404 controls from three rural California counties. Results: Overall, for the 2980 first‐degree relatives of PD cases, the risk of AD was not increased compared with the 2981 relatives of controls. But relatives of younger onset PD cases (≤60 years of age) were three times more likely to have received an AD diagnosis [hazard ratios (HR): 2.86; 95%CI: 1.44, 5.71]. Our data also suggest that some relatives of PD probands might be at a slightly increased risk of receiving an ET diagnosis, especially relatives of tremor dominant cases (HR: 1.69; 95%CI 0.99, 2.88), younger onset cases (HR: 2.03; 95%CI 0.93, 4.44), and male relatives (HR: 2.31; 95%CI 1.13, 4.73). In addition, fathers of cases were almost 15 years younger than fathers of controls when diagnosed with ET. Results were stable in sensitivity analyses. Conclusion: Our study suggests a familial susceptibility to AD amongst first‐degree relatives of younger onset PD cases.     

Seizures among families of Indian probands with different epileptic syndromes

OBJECTIVES: To investigate the contribution of hereditary factors in the causation of different epilepsy syndromes. MATERIAL AND METHODS: Occurrence of seizures among first- and second-degree relatives of 5628 Indian probands with epilepsy, and 3357 probands with non-epilepsy neurological disorders (who acted as control population) was documented. Syndromic concordance between epilepsy probands and affected relatives was investigated. RESULTS: Twenty percent epilepsy probands (1129) had affected relatives. Relatives of epilepsy probands were more often affected compared with relatives of non-epilepsy probands (OR: 3.4). Probands with some epilepsy syndromes more often had a positive family history. Relatives of younger probands were at greater risk of having epilepsy. Sibs were more often affected compared with other first- and second-degree relatives (OR: 1.3 and 4.6). Sibs having generalized epilepsies and syndromes and febrile convulsions (FC) were at greater odds of syndromic concordance with probands compared with second-degree relatives. Sibs and second-degree relatives having idiopathic/cryptogenic epilepsy had greater odds for concordance compared with those with symptomatic epilepsies. CONCLUSIONS: One-fifth of probands with all types of epileptic syndromes have family history of seizures. Familial risk of epilepsy correlated with the epilepsy syndrome among probands and their age at presentation. Risk of relatives being affected varied as a function of the relation with probands. Concordance of epilepsy syndromes varied both as a function of the epilepsy syndrome and relation with the probands.     

Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands

This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses.     

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest.     

Mild tremor in relatives of patients with essential tremor: what does this tell us about the penetrance of the disease?

BACKGROUND: Mild tremor may occur in relatives of patients with essential tremor (ET). However, this phenomenon has not been studied quantitatively or with a comparison group. Such a study may provide information on the penetrance of ET. OBJECTIVE: To obtain data on the magnitude of tremor in case and control relatives who did not meet diagnostic criteria for ET. METHODS: Cases with ET and control subjects from the Washington Heights-Inwood community in northern Manhattan, NY, were enrolled in a family study. Their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor, assigning a total tremor score (0-36 [maximum]). Data were analyzed on 201 case relatives and 212 control relatives who did not meet diagnostic criteria for ET. RESULTS: The mean total tremor score of first-degree case relatives was higher than that of first-degree control relatives (4.9 vs 3.9; P<.003). Total tremor scores for second-degree relatives did not differ (4.1 vs 4.2; P =.68). A larger percentage (55.2% vs 36.6%; P =.01) of first-degree case relatives had total tremor scores of 4 or more. Among first-degree relatives who were older than 60 years, 13 case relatives (59.1%) and 18 control relatives (45.0%) had total tremor scores of 4 or more. CONCLUSIONS: A considerable number of seemingly normal case relatives may have a genetic predisposition for tremor. Even among older case relatives (> or =60 years of age), there was an increased prevalence of higher tremor scores, suggesting that in that age group, subclinical ET may be present and penetrance still may not be complete.     

Prevalence and features of unreported dystonia in a family study of “pure” essential tremor

BackgroundEssential tremor (ET) is considered to be a highly heritable disorder, yet no susceptibility genes have been identified. The search for ET genes is severely hampered by clinical and genetic heterogeneity; the existence of this heterogeneity complicates the genetic analyses. We sought to determine the prevalence and clinical features of unreported dystonia in a family study of “pure” ET.MethodsET probands and their reportedly affected first-and second-degree relatives were enrolled in a genetics study, the Family Study of Essential Tremor (FASET) at Columbia University Medical Center. The goal was to enroll cases with “pure” ET (i.e., ET without dystonia or other neurological problems). Each enrollee underwent a detailed neurological evaluation.ResultsThere were 100 enrollees (28 probands, 72 relatives). Dystonia (primarily torticollis) occurred in 9 (32.1%) of 28 families, with 5 cases in one family, 2 cases in two families, and 1 case in six families. Those affected with dystonia included 3 (10.7%) probands and 12 (16.7%) relatives. There was a gender predilection: 14/15 (93.3%) with dystonia vs. 41/85 (48.2%) without dystonia were women (p = 0.001). Dystonia was previously undiagnosed in 14/15 (93.3%) cases.ConclusionsDystonia (esp. torticollis in women) was present in nearly one-third of the ET families in a genetics study, including 10.7% of ET probands. Dystonia was unreported and previously undiagnosed in nearly all of these individuals. The overarching biological issue is whether ET and dystonia should be regarded as one disease or two; this has obvious implications for the structuring of analyses in genetic studies.     

A family study of DSM-III-R schizoaffective disorder, depressive type, compared with schizophrenia and psychotic and nonpsychotic major depression

OBJECTIVE: To assess the validity of DSM-III-R schizoaffective disorder, the authors explored the morbid risks for schizophrenia and major affective disorders in the first-degree relatives of patients with schizoaffective disorder and relevant other diagnoses. METHOD: In addition to patients with DSM-III-R schizoaffective disorder, depressive type (N = 21), the probands included patients with mood-incongruent psychotic depression (N = 22), mood-congruent psychotic depression (N = 19), nonpsychotic depression (N = 27), or schizophrenia (N = 28) and normal subjects (N = 18). The patients were consecutively recruited from the outpatient facilities of a university psychiatry department; the normal subjects were students and nurses. All probands were directly interviewed, with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version (SADS-L), by a psychiatrist blind to information about relatives. Consenting relatives were directly interviewed, with the SADS-L, by two psychiatrists blind to the probands' diagnoses. The direct interview was supplemented--or replaced, when an interview was not possible (24%)--by family history data from all available sources. Morbid risks in relatives were calculated according to the Weinberg method. RESULTS: The relatives of the schizoaffective patients had almost the same risk for schizophrenia as the relatives of the schizophrenic patients. In the relatives of the patients mood-incongruent psychotic depression, the morbid risk for major affective disorders was about one-half that of the relatives of the patients with mood-congruent psychotic depression and one-third that of the relatives of the patients with nonpsychotic depression, but these differences did not reach statistical significance. CONCLUSIONS: These results suggest that DSM-III-R schizoaffective disorder is close to schizophrenia and largely corresponds to mainly schizophrenic schizoaffective disorder in the Research Diagnostic Criteria, whereas DSM-III-R mood-incongruent psychotic depression is probably quite heterogeneous and should be studied further.     

Lack of familial aggregation of Parkinson disease and Alzheimer disease

OBJECTIVE: To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls. DESIGN: Case-control study, family history method, and reconstructed cohort approach. METHODS: Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls. RESULTS: Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset (< or =50 years) and late-onset (>50 years) PD with relatives of controls. CONCLUSION: The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.     

Hippocampal volume in familial and nonfamilial schizophrenic probands and their unaffected relatives.

BACKGROUND: There is evidence for hippocampal volume loss in schizophrenia, but the etiology of this remains unclear. The aim of our study was to assess the contribution of familial liability and obstetric complications to hippocampal volume reduction in schizophrenia. METHODS: Hippocampal volumes were obtained using stereological methods from magnetic resonance scans performed on 35 schizophrenic probands from multiply affected families and 63 of their unaffected relatives, as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives, and 68 control subjects. RESULTS: Probands with schizophrenia, regardless of family history, had significant volume reduction of the left hippocampus. Hippocampal volume was not significantly reduced in either group of relatives. Obstetric complications were associated with left hippocampal volume reduction. CONCLUSIONS: We failed to find evidence that hippocampal volume loss is associated with familial liability to schizophrenia but have confirmed the association between hippocampal volume reduction and exposure to obstetric complications.     

Preponderance of female sex in the transmission of seizure liability in idiopathic generalized epilepsy

BACKGROUND: the predominance of the female sex in the transmission of seizure liability is a known phenomenon. However, all hitherto published genetic studies are based on reported seizure frequencies only. The aim of this investigation was to reexamine this problem by combining clinical and family EEG data. METHODS: families of 82 index cases fulfilling the following core criteria were ascertained; (1) definite clinical and EEG diagnosis of idiopathic generalized epilepsy with absences and/or myoclonic astatic seizures; (2) obtainable history and EEG recordings from both the parents and one or more siblings. EEG recordings were evaluated for different genetic traits of epileptiform EEG activity (EPA), as well as genetic characteristics of background activity. RESULTS: of the 164 parents 9% suffered from seizures. EPA was detected in 24% of probands' mothers versus 12% in fathers. Altogether 28% of probands' mothers were positive for seizures or EPA versus 16% of the fathers. Of parents with EPA in the EEG only about 50% showed seizures. Twenty one percent of all the parents and 60% of the mothers with EPA showed generalized alpha-activity (9% in controls). In contrast, in mothers without EPA a 'non alpha-EEG' was overrepresented. In probands' siblings, 14% showed seizures and 23% showed seizures or EPA. In probands' siblings with EPA seizure risk was 50 versus only 8% in siblings without EPA. The highest siblings risk was conferred by SW and an affected mother. If a father was affected, risk for the siblings of probands was almost equal to that in families with both the parents unaffected. Siblings of female probands were more often affected than those of male probands (19 vs. 8%; P<0.05). Generalized SW occurred in 17% of probands' siblings, in girls siblings significantly more often than in boys siblings (25 vs. 9%; P<0.01). CONCLUSION: clinical history and family EEG equally contribute information contents. Female preponderance in transmission of seizure liability is the result of a complex of genetic interactions that include the generalized alpha-EEG.     

Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study.

Essential tremor (ET) is a common condition that is present in as many as 23% of elderly individuals. Our objective was to determine the risk of ET and to study the impairment resulting from ET among relatives of ET cases compared to relatives of controls. ET cases and matched controls from the Washington Heights-Inwood community, New York, and their first- and second-degree relatives underwent a standardized tremor examination. The risk of having ET in relatives of cases vs relatives of controls was compared using Cox proportional hazards models. Five hundred ninety-one subjects were examined (59 ET cases, 72 controls, 234 case relatives, and 226 control relatives). ET was present in 25 (22.5%) of the 111 first-degree relatives of cases compared to 6 (5.6%) of 107 first-degree relatives of controls [relative risk (RR) = 4.67, 95% confidence interval (CI) = 1.90-11.49, p = 0.0008]. RRs were higher in relatives of cases with onset < or =50 years than in those with later onset (RR = 10.38 vs 4.82). Sixteen (64%) of twenty-five affected first-degree case relatives exhibited moderate tremor while performing tasks such as writing, drinking, or pouring. Relatives of ET patients are five times more likely to develop the disease than are members of the population and ten times more likely if the proband's tremor began at an early age. The majority of the affected relatives can expect to experience impairment resulting from tremor.     

Alzheimer's disease: genetic aspects and associated clinical disorders

Genetic aspects and associated clinical disorders were studied in a consecutive series of 68 men and women in whom Alzheimer's disease appeared at or before age 70. Secondary cases of dementia were found in 17 (25%) of the families, affecting 22 of the probands' siblings and parents. The cumulative incidence of Alzheimer's disease in these relatives was approximately 14% at age 75. An increased frequency of Down's syndrome was observed among relatives of the probands: a rate of 3.6 per 1,000, as compared with an expected rate of 1.3 per 1,000. A history of thyroid disease was established in 9 (19.6%) of the 46 female probands, a frequency greater than that reported in the general population. There was no excess of hematological malignancies among the blood relatives, and parental age at the time of birth of the probands did not differ from the norm. The results of this study indicate that early-onset Alzheimer's disease is associated with a genetic factor manifested in a substantial familial aggregation of dementia, a probable excess of Down's syndrome in the probands' relatives, and a possible association with thyroid dysfunction in women with this form of dementia.     

Family study of epilepsy in first degree relatives: data from the Italian Episcreen Study.

OBJECTIVE: To evaluate the family history of epilepsy in first degree relatives of probands with epilepsy. METHODS: A sample of 10787 patients with epilepsy with complete information about first degree relatives (parents, siblings and offspring) was selected from the database of the Episcreen Project, the largest Italian observational study on epilepsy. Family history was assessed by: (1) prevalence estimates of epilepsy among proband's relatives, (2) modified cumulative risks (MCR), adjusted using proband's age as censoring time in life tables, (3) standardised morbidity ratios (SMR), using a sub-group of symptomatic epilepsies as control group. RESULTS: Patients (9.1%) had a family history of epilepsy. The overall prevalence of epilepsy among first degree relatives was 2.6%. Idiopathic generalised epilepsies had the highest prevalence (5.3%). Cryptogenetic epilepsies had a lower prevalence (2.1%) than idiopathic epilepsies, but higher then symptomatic epilepsies (1.5%), both in generalised and focal forms (3.8% vs. 2.0% and 1.8% vs. 1.3%). A similar tendency was detected using MCR and SMR, with the higher values of risks/ratios for idiopathic and generalised epilepsies. Probands with idiopathic generalised epilepsies were highly concordant with respect to their relatives' type of epilepsy. Considering other strata factors, risks were higher in proband's epilepsies with an onset less then 14 years of age, while sex played no definite role in differentiating the family history. CONCLUSIONS: The Episcreen model permits a variety of stratification factors to measure family risk, including age at onset, epilepsy localisation and aetiology with a large sample of more than 10,000 probands and 1065/40,544 relatives affected and classified.