Background PAPA syndrome is a recently identified hereditary autoinflammatory syndrome clinically characterized by pyogenic arthritis, severe acne, and pyoderma gangrenosum. It is caused by mutations in the PSTPIP1 gene and may be closely linked to the aseptic abscesses syndrome, which has been shown to be associated with CCTG repeat amplification in the promoter region of PSTPIP1. Objective We describe two unrelated patients with a clinical presentation quite similar to, yet distinct from, PAPA syndrome. Results Both patients had pyoderma gangrenosum and acute or remittent acne conglobata, but, in contrast to PAPA syndrome, lacked any episodes of pyogenic arthritis. Instead, they had suppurative hidradenitis. Mutations in PSTPIP1 exons 1 to 15 were excluded. In the promoter region, an increased repetition of the CCTG microsatellite motif was present on one allele in both patients. Alterations of the most commonly affected exons of the MEFV , NLRP3 , and TNFRSF1A genes also were not detectable. One patient was treated with the interleukin (IL)-1 receptor antagonist anakinra and responded well, although without complete remission. This implies that IL-1ß may be of pathogenetic importance. Limitations Small number of patients, no gene mutation identified, and unclear efficacy of therapy are limitations. Conclusions The clinical triad of pyoderma gangrenosum, acne, and suppurative hidradenitis represents a new disease entity within the spectrum of autoinflammatory syndromes, similar to PAPA and aseptic abscesses syndrome. For this disease, we propose the acronym “PASH” syndrome. PASH syndrome may respond to IL-1ß blockade.
Highlights • These consensus criteria update the 2003 diagnostic criteria for RLS/WED. • A new essential criterion, differential diagnosis, improves diagnostic specificity. • The clinical significance of RLS/WED is determined by a new specifier. • A course specifier classifies RLS/WED as chronic-persistent or intermittent. • The pediatric diagnostic criteria have been merged with the adult criteria.
The euglycemic-hyperinsulinemic clamp is not available in most clinical settings. An accessible and inexpensive measurement for identifying insulin resistance (IR) is necessary. Our aim is to assess whether the adiponectin (ADI) index (ADI/[FBG x FIns]) is a better surrogate index for the assessment of IR or metabolic syndrome (MetS). A population-based cross-sectional study was conducted including 100 healthy women and 99 polycystic ovary syndrome patients. The euglycemic-hyperinsulinemic clamp was performed. Circulating ADI levels were determined by ELISA. Polycystic ovary syndrome and polycystic ovary syndrome plus MetS subjects had higher products of fasting triglycerides and glucose (TyG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), increased ratios of the area under the curve for insulin/the area under the curve for glucose (AUCi/AUCg), but lower ADI index as compared with healthy subjects. Partial correlation analysis in all populations showed that the M-value was significantly negatively correlated with HOMA-IR, TyG, TG/HDL, and AUCi/AUCg, and correlated positively with the ADI index. The r value of Pearson correlation between the ADI index and M-value was greater than that of the correlation between HOMA-IR, TyG, TG/HDL-C, and AUCi/AUCg. The optimal cut-off value of the ADI index for detection of IR was 0.67, with a sensitivity of 89.4% and a specificity of 88.1%, whereas for detection of MetS, it was 0.32, with a sensitivity of 88.7% and a specificity of 71.0%. The ADI index may be a surrogate marker in detecting IR and MetS.
To determine the prevalence and clinical characteristics of comorbid obsessive compulsive disorders and syndromes (OCD/OCS), compared with pure OCD/OCS among adults in the community.Data were drawn from the Zurich Study, a longitudinal cohort study of 591 adults in the canton of Zurich. Comorbid OCD/OCS was compared with pure OCD/OCS groups in terms of distress, impairment, family history, suicide behavior and treatment using multivariable logistic regression analyses.OCD was significantly comorbid with bipolar I/II and minor bipolar disorders, anxiety states (GAD, repeated panic attacks) and social phobia, whereas there was no clear association between OCD and major depressive disorder or phobias other than social phobia. Results suggest that comorbid OCD/OCS is common among adults in the community, with the majority of those with OCD/OCS having at least one comorbid mood or anxiety disorder with a prevalence of 7.4% compared to 4.8% of remaining OCD/OCS. Comorbidity of OCD/OCS and anxiety states was more common among women (85.6 %) and comorbidity with bipolar spectrum was more common among men (69.6%). Comorbid OCD/OCS was associated with significantly higher levels of treatment seeking, impairment,distress and suicidality compared with pure OCD/OCS. Comorbidity with bipolar disorders significantly increased the risk for alcohol abuse/dependence.Comorbidity of OCD/OCS with bipolar disorder and bipolar spectrum disorders is common and very probably explains the association between OCD and depression found in other studies. The early recognition of bipolar/cyclothymic OCD/OCS may help to prevent the abuse of/dependence on alcohol.
OBJECTIVE-In the French Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, cross-sectional analyses have shown that a higher consumption of dairy products and calcium are associated with a lower prevalence of the metabolic syndrome (MetS). We assess the influence of dairy products on 9-year incident MetS and on impaired fasting glycemia and/or type 2 diabetes (IFG/T2D). RESEARCH DESIGN AND METHODS-Men and women who completed a food frequency questionnaire at baseline and after 3 years were studied (n = 3,435). Logistic regression models were used to study associations between the average year 0 and year 3 consumption of milk and dairy products, cheese, dietary calcium density, and incident MetS and IFG/T2D after adjusting for 1) sex, age, alcohol, smoking, physical activity, fat intake and 2) additionally for BMI. Associations between dairy products and continuous variables were studied by repeated-measures ANCOVA, using the same covariates. RESULTS-Dairy products other than cheese, and dietary calcium density, were inversely associated with incident MetS and IFG/T2D, cheese was negatively associated with incident MetS. All three parameters were associated with lower diastolic blood pressure, and with a lower EM! gain. Higher cheese intake and calcium density were associated with a lower increase in waist circumference and lower triglyceride levels. Calcium density was also associated with a lower systolic blood pressure and a lower 9-year increase in plasma triglyceride levels. CONCLUSIONS-A higher consumption of dairy products and calcium was associated with a lower 9-year incidence of MetS and IFG/T2D in a large cohort drawn from the general population. Diabetes Care 34:813-817, 2011
Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex chromosomal aneuploidies had positive predictive values of 26% for monosomy X, 50% for 47,XXX, and 86% for 47,XXY. The positive predictive values for detection of common autosomal and sex chromosomal aneuploidies by cell-free fetal DNA screening were comparable with other studies. Identification of microdeletions was associated with lower positive predictive values and higher false-positive rates, likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell-free fetal DNA screening tests. Improvement of the cell-free fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility. Nonetheless, our data provide valuable information that may aid result interpretation, patient counseling, and clinical decision making/management.
Abstract Background – PCOS is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive age women with PCOS are at increased risk of metabolic syndrome however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. Objectives To compare the prevalence of metabolic syndrome and clustering of its components in women with PCOS in the United States with women in India, Brazil, Finland, and Norway. Study Design This is a cross-sectional study performed in 1089 women with PCOS from 1999-2016 in five outpatient clinics in the United States, India, Brazil, Finland and Norway. PCOS was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure (BP), body mass index (BMI), fasting high-density lipoprotein cholesterol (HDL-C), fasting triglycerides (TG), fasting glucose. Data from all sites were re-evaluated for appropriate application of diagnostic criteria for PCOS, identification of PCOS phenotype and complete metabolic work-up. The US white women with PCOS were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. Results The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism (15.6±6.5, p<0.001) . The age-adjusted OR for metabolic syndrome was highest in U.S. Black women [4.52 (95% CI 2.46-8.35)] compared with U.S. White women. When adjusted for age and body mass index, the prevalence was similar in the two groups. Significantly more Black women met body mass index and blood pressure criteria (p< 0.001), and fewer met fasting triglycerides criteria (p < 0.05). The age- and body mass index - adjusted prevalence of metabolic syndrome was highest in Indian women [OR 6.53 (95% CI 3.47-12.30]) with abnormalities in glucose and fasting high-density lipoprotein cholesterol criterion and in Norwegian women (OR 2.16 (95% CI 1.17-3.98)] with abnormalities in blood pressure, glucose and fasting high-density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US white women. Conclusion Despite a unifying diagnosis of PCOS, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with PCOS, such that compared to Caucasian women from the US, Black US women had the highest prevalence, whereas women from India and Norway have a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive age women.
Background Self‐injurious and aggressive behaviours are reported as components of some behavioural phenotypes but there are few studies comparing across syndrome groups. In this study we examined the prevalence of these behaviours and the associated person characteristics in seven genetic syndromes. Methods Questionnaire data on self‐injury and aggression, mood, hyperactivity, autism spectrum disorder and repetitive behaviour were collected on Angelman (AS, n = 104), Cornelia de Lange (CdLS, 101), Cri du Chat (CdCS, 58), Fragile X (FXS, 191), Lowe (LS, 56), Prader–Willi (PWS, 189) and Smith–Magenis (SMS, 42) syndromes. Results A significantly higher prevalence of self‐injury was evident in CdCS, CdLS, FXS, PWS, LS and SMS. The prevalence of aggression was significantly heightened in AS and SMS. Self‐injury was associated with repetitive and impulsive behaviour in CdLS, FXS, PWS and LS. Impulsivity and overactivity were significantly higher in those showing aggression across all syndrome groups. Conclusions These data quantify the risk for self‐injury and aggression in the syndromes studied with implications for early intervention. The associations between these behaviours and person characteristics both within and between syndromes warrant further research.
Background: The most commonly reported phenotypes described in patients with PTEN mutations are Bannayan–Riley–Ruvalcaba syndrome (BRRS), with childhood onset, macrocephaly, lipomas and developmental delay, and Cowden Syndrome (CS), an adult-onset condition recognised by mucocutaneous signs, with a risk of cancers, in particular those of the thyroid and breast. It has been suggested that BRRS and CS are the same condition, but the literature continues to separate them and seek a genotype–phenotype correlation. Objective: To study the clinical features of patients with known PTEN mutations and observe any genotype–phenotype correlation. Methods: In total, 42 people (25 probands and 17 non-probands) from 26 families of all ages with PTEN mutations were recruited through the UK clinical genetics services. A full clinical history and examination were undertaken. Results: We were unable to demonstrate a genotype–phenotype correlation. Furthermore, our findings in a 31-year-old woman with CS and an exon 1 deletion refutes previous reports that whole exon deletions are only found in patients with a BRRS phenotype. Conclusion: Careful phenotyping gives further support for the suggestion that BRRS and CS are actually one condition, presenting variably at different ages, as in other tumour-suppressor disorders such as neurofibromatosis type 1. This has important counselling implications, such as advice about cancer surveillance, for children diagnosed with BRRS.