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Ectodermal dysplasias: a new clinical-genetic classification.

ABSTRACT: The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.The anomalies affecting the epidermis and epidermal appendages are extremely variable and clinical overlap is present among the majority of EDs. Most EDs are defined by particular clinical signs (for example, eyelid adhesion in AEC syndrome, ectrodactyly in EEC). To date, few causative genes have been identified for these diseases. We recently reviewed genes known to be responsible for EDs in light of their molecular and biological function and proposed a new approach to EDs, integrating both molecular-genetic data and corresponding clinical findings. Based on our previous report, we now propose a clinical-genetic classification of EDs, expand it to other entities in which no causative genes have been identified based on the phenotype, and speculate on possible candidate genes suggested by associated "non-ectodermal" features.

SUBMITTER: Priolo M

PROVIDER: S-EPMC1734928 | biostudies-other | 2001 Sep

REPOSITORIES: biostudies-other

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Ectodermal dysplasias: a new clinical-genetic classification.

Priolo M M Laganà C C

Journal of medical genetics 20010901 9

The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.The anomalies affecting the epidermis and epidermal appendages are ex ...[more]

PMID: 11546825

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Project description:Background The New York Heart Association (NYHA) classification has served as a fundamental tool for risk stratification of heart failure (HF) and determines clinical trial eligibility and candidacy for drugs and devices. However, its ability to adequately stratify risk is unclear. Methods and Results To compare NYHA class with objective assessments and survival in patients with HF, we performed secondary analyses of 4 multicenter National Institutes of Health-funded HF clinical trials that included patients classified as NYHA class II or III: TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist), DIG (The Effect of Digoxin on Mortality and Morbidity in Patients With Heart Failure), HF-ACTION (Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure), and GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure). Twenty-month cumulative survival was compared between classes using Kaplan-Meier curves and the log rank test. NT-proBNP (N-terminal pro-B-type natriuretic peptide), Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, 6-minute walk distances, left ventricular ejection fraction, and cardiopulmonary test parameters were compared using Wilcoxon rank sum tests and percentage overlap using kernel density estimations. Cumulative mortality varied significantly across NYHA classes and HF clinical trials (likelihood ratio, P<0.001). Mortality at 20 months for NYHA class II ranged from 7% for patients in HF-ACTION to 15% in GUIDE-IT, whereas mortality for NYHA class III ranged from 12% in TOPCAT to 26% in GUIDE-IT. There was substantial percentage overlap in values for NT-proBNP levels (79% and 69%), KCCQ scores (63% and 54%), 6-minute walk distances (63% and 54%), and left ventricular ejection fraction (88% and 83%). Similarly, there was substantial overall in values for minute ventilation-carbon dioxide production relationship (71%), maximal oxygen uptake (54%), and exercise duration (53%). Conclusions The NYHA system poorly discriminates HF patients across the spectrum of functional impairment. These findings raise important questions about the need for improved phenotyping of these patients to facilitate risk stratification and response to interventions.

Project description:Histological grading of breast cancer defines morphological subtypes informative of metastatic potential, although not without considerable inter-observer disagreement and clinical heterogeneity particularly among the moderately differentiated grade II (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade I (G1) and grade III (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with moderately differentiated disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable to that of lymph node status and tumor size. When incorporated into the Nottingham Prognostic Index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low and high grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression. Three separate breast cancer cohorts were analyzed: 1) Uppsala (n=249), 2) Stockholm (n=58), 3) Singapore (n=40). The Uppsala and Singapore data can be accessed here. The Stockholm cohort data can be accessed at GEO Series GSE1456. Keywords: Tumor sample comparisons

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Ectodermal dysplasias: a new clinical-genetic classification.

Publications

Ectodermal dysplasias: a new clinical-genetic classification.

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