{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:08:01Z","timestamp":1792163281179,"version":"4.4.0"},"reference-count":16,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p>The epidemiology and genetics of microtia-anotia (M-A) were studied using data collected from the Italian Multicentre Birth Defects Registry (IPIMC) from 1983 to 1992. Among 1,173, 794 births, we identified 172 with M-A, a rate of 1.46\/10,000; 38 infants (22.1%) had anotia. Of the 172 infants, 114 (66.2%) had an isolated defect, 48 (27.9%) were multiformed infants (MMI) with M-A, and 10 (5.8%) had a well defined syndrome. The frequency of bilateral defects among non-syndromic cases was 12% compared to 50% of syndromic cases (p = 0.007). Among the MMI only holoprosencephaly was preferentially associated with M-A (four cases observed upsilon 0.7 expected, p = 0.005). No significant variations were identified in the prevalence of non-syndromic cases by geographical area (range 0.62-2.37\/10,000 births) or by five month time periods (range 0.21-2.58\/10,000 births), nor was there evidence of time trends. When M-A cases were compared to controls, we found that mothers with parity 1 had a higher risk of giving birth to an MMI with M-A, and that mothers with chronic maternal insulin dependent diabetes were at significantly higher risk for having a child with M-A. MMI with M-A had higher rates of prematurity, low birth weight, reduced intrauterine growth, and neonatal mortality than infants with isolated M-A and controls. Babies with isolated M-A had, on average, a lower birth weight than controls; the difference was higher for females. The analysis of pedigrees and familial cases suggests an autosomal dominant trait with variable expression and incomplete penetrance in a proportion of cases, or a multifactorial aetiology. Three cases had consanguineous parents, but the absence of M-A among previous sibs does not support autosomal recessive inheritance.<\/jats:p>","DOI":"10.1136\/jmg.32.6.453","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"453-457","source":"Crossref","is-referenced-by-count":163,"title":["Epidemiology and genetics of microtia-anotia: a registry based study on over one million births."],"prefix":"10.1136","volume":"32","author":[{"given":"P","family":"Mastroiacovo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Corchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L D","family":"Botto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Lanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Zampino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1995,6,1]]},"reference":[{"key":"ref_1","article-title":"External ear","volume-title":"malformations and related anonmalies. Volume II","author":"Carey, J.C.","unstructured":"Carey JC. External ear. In: Stevenson ED, Hall JG, Goodman RM, eds. Human malformations and related anonmalies. Volume II. Oxford: Oxford University Press, 1993:193204."},{"key":"ref_2","first-page":"113","article-title":"Microtia in New Mexico: evidence for multifactorial causation. In: Numerical taxonomy of birth defects and polygenic disorders. Birth Defects: Original Article Series, XIII(3A)","author":"Aase, J.M.; Tegtmeier, R.E.","year":"1977","unstructured":"Aase JM, Tegtmeier RE. Microtia in New Mexico: evidence for multifactorial causation. In: Numerical taxonomy of birth defects and polygenic disorders. Birth Defects: Original Article Series, XIII(3A). White-Plains: National Foundation March of Dimes, 1977: 113-16."},{"key":"ref_3","first-page":"7","article-title":"Craniofacial changes in unilateral microtia. An anthropometric study. _7 Craniofac Genet Develop Biol","volume":"4","author":"Smahel, Z.; Horak, I.","year":"1984","unstructured":"Smahel Z, Horak I. Craniofacial changes in unilateral microtia. An anthropometric study. _7 Craniofac Genet Develop Biol 1984; 4: 7-16."},{"key":"ref_4","article-title":"International Clearinghouse for Birth Defects Monitoring Systems. Congenital malformations worldwide","year":"1991","unstructured":"International Clearinghouse for Birth Defects Monitoring Systems. Congenital malformations worldwide. Amsterdam: Elsevier, 1991."},{"key":"ref_5","first-page":"364","article-title":"External ear malformations: epidemiology, genetics, and natural history","volume":"6","author":"Melnick, M.; Myrianthopoulos, N.C.","year":"1979","unstructured":"Melnick M, Myrianthopoulos NC. External ear malformations: epidemiology, genetics, and natural history. Birth Defects 1979;XV(9). 6 Castilla EE, Orioli IM. Prevalence rates of microtia in South America. Int J Epidemiol 1986;15:364-8.","journal-title":"Birth Defects; Castilla EE, Orioli IM. Prevalence rates of microtia in South America"},{"key":"ref_6","first-page":"23","article-title":"L'Indagine Policentrica Italiana sulle Malformazioni Congenite: un progetto collaborativo pilota finalizzato alla sorveglianza delle malformazioni congenite","volume":"45","author":"Mastroiacovo, P.; Musacchio, P.; Bertollini, R.","year":"1982","unstructured":"Mastroiacovo P, Musacchio P, Bertollini R. L'Indagine Policentrica Italiana sulle Malformazioni Congenite: un progetto collaborativo pilota finalizzato alla sorveglianza delle malformazioni congenite. Prosp Pediatr 1982;45:23-38.","journal-title":"Prosp Pediatr"},{"key":"ref_7","first-page":"17","article-title":"The Italian Birth Defects Monitoring System. Baseline rates based on 183,453 births and comparison with other registries","volume-title":"biological and clinical research. Volume 114, Part B. Epidemiology, early detection and therapy, and environnmental factors","author":"Mastroiacovo, P.","year":"1985","unstructured":"Mastroiacovo P. The Italian Birth Defects Monitoring System. Baseline rates based on 183,453 births and comparison with other registries. In: Marois M, ed. Progress in biological and clinical research. Volume 114, Part B. Epidemiology, early detection and therapy, and environnmental factors. New York: Alan R Liss, 1985:17-21."},{"key":"ref_8","first-page":"620","article-title":"Die Missbildungen des Ohres. In: Henke F, Lubarsch 0, eds. Handbuch der Spez Path Aanat Hist","author":"Marx, H.","unstructured":"Marx H. Die Missbildungen des Ohres. In: Henke F, Lubarsch 0, eds. Handbuch der Spez Path Aanat Hist. Berlin: Springer, 1926:620-5."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3233\/JRS-1991-2504","article-title":"An ICBDMS collaborative study: monitoring multiformed infants","volume":"2","author":"Mastroiacovo, P.","year":"1991","unstructured":"Mastroiacovo P. An ICBDMS collaborative study: monitoring multiformed infants. Int J Risk Safety Med 1991;2: 255-70.","journal-title":"Int J Risk Safety Med"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/ajmg.1320370213","article-title":"On the measurement and interpretation of birth defect associations in epidemiologic studies","volume":"37","author":"Khoury, M.J.; James, L.M.; Erickson, J.D.","year":"1990","unstructured":"Khoury MJ, James LM, Erickson JD. On the measurement and interpretation of birth defect associations in epidemiologic studies. Am J Med Genet 1990;37:229-36.","journal-title":"Am J Med Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/oxfordjournals.epirev.a036030","article-title":"The measurement of social class in epidemiology","volume":"1","author":"Liberatos, P.; Link, B.G.; Kelsey, J.L.","year":"1988","unstructured":"Liberatos P, Link BG, Kelsey JL. The measurement of social class in epidemiology. Epidemiol Res 1988;1O:87-121.","journal-title":"Epidemiol Res"},{"key":"ref_12","first-page":"624","article-title":"Standard di peso alla nascita in Italia","volume":"9","author":"Parazzini, F.; Bortolous, R.","year":"1993","unstructured":"Parazzini F, Bortolous R. Standard di peso alla nascita in Italia. Medico e Bambino 1993; 9: 624-8."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/tera.1420420508","article-title":"and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance","volume":"42","author":"Lynberg, M.C.; Khoury, M.J.; Lammer, E.J.","year":"1990","unstructured":"Lynberg MC, Khoury MJ, Lammer EJ, et al. Sensitivity, specificity, and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance. Teratology 1990;42:513-9.","journal-title":"Teratology"},{"key":"ref_14","first-page":"70","article-title":"Congenital malformations. A report of a study of series of consecutive births in 24 centres","volume":"34","author":"Stevenson, A.C.; Johnston, H.A.; Stewart, M.I.P.; Golding, D.","year":"1996","unstructured":"Stevenson AC, Johnston HA, Stewart MIP, Golding D. Congenital malformations. A report of a study of series of consecutive births in 24 centres. Bull WHO 1996;suppl 34:70-1.","journal-title":"Bull WHO"},{"key":"ref_15","series-title":"Proceedings of the First International Meeting of the Genetic and Reproductive Epidemiology Research Society (GRERS)","first-page":"71","article-title":"Epidemiological and genetic study of holoprosencephaly in 106 cases observed in the Italian Multicentric Registry 1978-1989","author":"Mastroiacovo, P.; Botto, L.D.; Cavalcanti, D.P.","year":"1992","unstructured":"Mastroiacovo P, Botto LD, Cavalcanti DP, et al. Epidemiological and genetic study of holoprosencephaly in 106 cases observed in the Italian Multicentric Registry 1978-1989. In: Mastroiacovo P, Kallen B, Castilla EE, eds. Proceedings of the First International Meeting of the Genetic and Reproductive Epidemiology Research Society (GRERS). Milano: Ghedini Editore 1992:71-82."},{"key":"ref_16","first-page":"438","article-title":"The lacrimoauricolo-dento-digital (LADD) syndrome","volume":"83","author":"Hollister, D.W.; Klein, S.H.; Dejager, H.J.","year":"1973","unstructured":"Hollister DW, Klein SH, Dejager HJ, et al. The lacrimoauricolo-dento-digital (LADD) syndrome. _7 Pediatr 1973; 83:438-44."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.32.6.453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:57:15Z","timestamp":1759723035000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.32.6.453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,6]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1995,6,1]]},"published-print":{"date-parts":[[1995,6]]}},"alternative-id":["10.1136\/jmg.32.6.453"],"URL":"https:\/\/doi.org\/10.1136\/jmg.32.6.453","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,6]]}}}