Men with FMR1 premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset condition characterised by cerebellar ataxia and intention tremor, usually found in individuals with FMR1 premutation alleles (PM—CGG expansion of 55–199 repeats). Population studies estimate that between 1 in 250 and 1 in 1600 men have a PM, with up to 45% of these men suggested to develop FXTAS by age 80. We used a Bayesian approach to compare the probability of finding a specific PM genotype in an ataxia population to a population control group and found an estimated penetrance of <1% (0.031%; CI 0.007% to 0.141%) for men with ≤70 CGGs. These findings suggest that men with a PM of ≤70 CGGs, who comprise the vast majority of those with a PM, have a much lower risk of being affected with FXTAS than previously suggested. This is an issue of growing importance for accurate genetic counselling, as those with a PM of ≤70 CGGs are increasingly detected through community carrier screening or neurodevelopmental assessment programmes.

Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders

Background: Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders. Methods: We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85th percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. Results: Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight. Conclusions: Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.

Higher Prevalence of Obesity among Children with Functional Abdominal Pain Disorders

Background Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders. Methods We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85th percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. Results Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight. Conclusions Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.

Long-term health of women with genetic POI due to FSH-resistant ovaries

Objective To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO). Design A prospective follow-up study in a university-based tertiary clinic setting. Methods Twenty-six women with an inactivating A189V FSH receptor mutation were investigated by means of a health questionnaire and clinical examination. Twenty-two returned the health questionnaire and 14 were clinically examined. Main outcome measures in the health questionnaire were reported as HT, morbidity, medication and infertility treatment outcomes. In the clinical study, risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS) were compared to age-matched controls from a national population survey (FINRISK). Average number of controls was 326 per FSHRO subject (range 178–430). Bone mineral density and whole-body composition were analyzed with DXA. Psychological and sexual well-being was assessed with Beck Depression Inventory (BDI21), Generalized Anxiety Disorder 7 (GAD-7) and Female Sexual Function Index (FSFI) questionnaires. Results HT was initiated late (median 18 years of age) compared with normal puberty and the median time of use was shorter (20–22 years) than the normal fertile period. Osteopenia was detected in 9/14 of the FSHRO women despite HT. No major risk factors for CVD or diabetes were found. Conclusions HT of 20 years seems to be associated with a similar cardiovascular and metabolic risk factor profile as in the population control group. However, optimal bone health may require an early-onset and longer period of HT, which would better correspond to the natural fertile period.

CYP4F2 (rs2108622) Gene Polymorphism Association with Age-Related Macular Degeneration

Background. Age-related macular degeneration is the leading cause of blindness in elderly individuals where aetiology and pathophysiology of age-related macular degeneration are not absolutely clear.Purpose. To determine the frequency of the genotype of rs2108622 in patients with early and exudative age-related macular degeneration.Methods. The study enrolled 190 patients with early age-related macular degeneration, 181 patients with exudative age-related macular degeneration (eAMD), and a random sample of 210 subjects from the general population (control group). The genotyping of rs2108622 was carried out using the real-time polymerase chain reaction method.Results. The analysis of rs2108622 gene polymorphism did not reveal any differences in the distribution of C/C, C/T, and T/T genotypes between the early AMD group, the eAMD group, and the control group. TheCYP4F2(1347C>T)T/Tgenotype was more frequent in males with eAMD compared to females (10.2% versus 0.8%;p=0.0052); alsoT/Tgenotype was less frequently present in eAMD females compared to healthy control females (0.8% versus 6.2%;p=0.027).Conclusion. Rs2108622 gene polymorphism had no predominant effect on the development of early AMD and eAMD. TheT/Tgenotype was more frequent in males with eAMD compared to females and less frequently present in eAMD females compared to healthy females.

Canadian Health Databases Relevant To Great Lakes Basin Research

Several population-based health databases exist in Canada which provide valuable systematic information for facilitating epidemiological evaluation of human health in the Great Lakes Basin. They include the long-established Canadian Mortality Database, a national birth defects registry, a provincial hospitalization database, and provincial and national cancer registry systems. The most recent addition is the National Enhanced Cancer Surveillance System which currently is being implemented to allow for detailed evaluation of air and water quality concerns in relation to a range of cancer types. The system includes statistical evaluation of geographical cancer incidence patterns; development of a national environmental quality database; and systematic collection of individual risk factor information for a large number of newly diagnosed cancer cases and a population control group. A brief description of each database and examples of relevant research using each of these databases is presented.

Mental Illness in Sibships of Two and Three

A conspicuous deficiency of practically all birth order studies is the absence of a general population control group. Instead, a number of statistical methods of estimating the expected number of subjects in each sibling position have been used. These are based upon the assumption that for any given size of sibship there should be equal numbers of subjects in each birth rank. As Price and Hare (1969) have pointed out, there are a number of reasons why such as assumption is incorrect, and therefore why the conclusions based upon it are unreliable. Because, in most studies, only relatively small numbers of patients are available various methods of combining sibships of different sizes are adopted and the sexes of the siblings are ignored. To consider a sibling position irrespective of the size and composition of the sibship in which it occurs is unjustifiable. As birth order effects are relatively slight, large numbers of subjects are required to detect them. Unless a patient sample of several thousand is used the numbers in any sibship size are too small to permit analysis by birth rank. As sibship size is itself a possible variable, and as within each sibship the sexes of the siblings can be distributed in a variety of ways, birth order studies should ideally consider one sibship size at a time and should investigate sibling position by sex of sibling. Unfortunately, in sibships of four or more the numbers of combinations become so great as to render this approach impracticable.

The Relationship between Attempted Suicide, Depression and Parent Death

The present study is one of a series of investigations concerned with the relationship between parent death and mental illness. In previous studies (Birtchnell 1970 a and b) it has been shown that significantly more psychiatric patients, compared with a general population control group, experienced parent death during the first five years of life and during a period of one to five years before admission to hospital. It was further shown (Birtchnell 1970c) that within the patient group, though the incidence of early and recent parent death was similar among depressed and non-depressed patients, the severely depressed compared with the moderately depressed patients experienced sig- nificandy more parental bereavements during the first twenty years of life and during a period of one to twenty years before admission. In a large sample of depressed in-patients, Hill (1969) demonstrated a significant excess of early parent deaths in those who attempted suicide, and he suggested that this might be secondary to the association between early parent death and severe depression.