{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:49:27Z","timestamp":1776257367274,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,5,16]],"date-time":"2005-05-16T00:00:00Z","timestamp":1116201600000},"content-version":"vor","delay-in-days":3745,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1995,2,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Numerical taxonomy is defined by Sneath and Sokal as the grouping of taxonomic units on the basis of their character states by numerical methods of multivariate data analysis, and syndromology as the study of multiple congenital anomaly (MCA) syndromes and of their nosology. We present here an application of those methods to the analysis of overlapping syndromes. The main advantage of numerical taxonomy is that it allows simultaneous objective and unweighted analysis of multiple traits, giving the possibility to test mathematically the clinical hypotheses about the heterogeneity between closely resembling syndromes and uncovering objective patterns of anomalies, to be compared with the subjective pattern recognition process which characterizes most of the diagnostic approach in syndromology. In this paper, we explored 5 syndromes whose most severe expression belongs to the cerebroacrovisceral early lethality (CAVE) phenotype: hydrolethalus, severe Smith\u2010Lemli\u2010Opitz, orofaciodigital type VI (Varadi\u2010Papp), holoprosencephaly\u2010polydactyly, and Pallister\u2010Hall syndromes, Fifty\u2010five published cases, including many overlapping cases, were submitted to principal factor analysis followed by hierarchical clustering and graphical scaling. Results show that the 5 syndromes clearly constitute independent phenotypic entities, that some of the original diagnoses have to be reconsidered, and that many of the overlapping cases may be unambiguously set in one category. Hypothalamic hamartoblastoma appears to be a nonspecific dysplasia occurring in any of the 5 disorders. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320550410","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T17:54:26Z","timestamp":1118512466000},"page":"433-443","source":"Crossref","is-referenced-by-count":14,"title":["Numerical syndromology: A mathematical approach to the nosology of complex phenotypes"],"prefix":"10.1002","volume":"55","author":[{"given":"Alain","family":"Verloes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,5,16]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"463","article-title":"Holoprosenc\u00e9phalie, polydactylie, cardiopathie: nouveau syndrome ou nouveau cas d'hydrolethalus","volume":"36","author":"Andr\u00e9 SA","year":"1988","journal-title":"J G\u00e9n\u00e9t Hum"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260418"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.21.1.34"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.27.1.50"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320260110"},{"key":"e_1_2_1_7_1","volume-title":"Multivariate Analysis","author":"Dillon WR","year":"1984"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280323"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420111"},{"issue":"3","key":"e_1_2_1_10_1","first-page":"5","article-title":"Objective methods for classification and the study of birth defects","author":"Estabrook GF","year":"1977","journal-title":"Birth Defects"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210104"},{"key":"e_1_2_1_12_1","volume-title":"Applied Multivariate Data Analysis","author":"Everitt B","year":"1991"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320400403"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250609"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320070110"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320410220"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320330416"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.25.2.88"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.20.6.433"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320410436"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320350310"},{"issue":"2","key":"e_1_2_1_22_1","first-page":"161","article-title":"The C syndrome of multiple congenital anomalies","author":"Opitz JM","year":"1969","journal-title":"BDOAS"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420090109"},{"issue":"3","key":"e_1_2_1_24_1","first-page":"13","article-title":"The polythetic (phenotypic community) system of classifying human malformation syndromes","author":"Pinsky L","year":"1977","journal-title":"Birth Defects"},{"issue":"5","key":"e_1_2_1_25_1","first-page":"93","article-title":"The numerical versus intuitive approach to syndrome nosology","author":"Preus M","year":"1980","journal-title":"Birth Defects"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1983.tb00430.x"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210216"},{"issue":"3","key":"e_1_2_1_28_1","first-page":"31","article-title":"An application of numerical taxonomy to the classification of syndromes","volume":"13","author":"Preus M","year":"1977","journal-title":"Birth Defect"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320160303"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320190208"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1981.tb00718.x"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470305"},{"key":"e_1_2_1_33_1","volume-title":"Numerical Taxonomy: The Principle and Practice of Numerical Classiffication","author":"Sneath PHA","year":"1973"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.17.2.119"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.5.297"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320430404"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","unstructured":"VerloesA NarcyF Fallet\u2010BiancoC(1994): Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence microphthalmia pulmonary malformations radial hypoplasia and M\u00fcllerian regression. Further delineation of a new syndrome?Clin Dysmorphol(in press).","DOI":"10.1097\/00019605-199501000-00004"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320550410","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320550410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T21:29:48Z","timestamp":1698355788000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320550410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2,13]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1995,2,13]]}},"alternative-id":["10.1002\/ajmg.1320550410"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320550410","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2,13]]}}}