The prevalence of 55 well-defined mild errors of morphogenesis (MEMs) was determined in 100 children with acute lymphoblastic leukemia (ALL), their 80 sibs, 91 mothers, and 76 fathers. Seventy-four patients were treated in Pe ´cs (Hungary) and 26 in Tu ¨bingen (Germany). Only white Caucasian index c
Errors of morphogenesis and developmental field theory
✍ Scribed by Mart�nez-Fr�as, Maria-Luisa; Fr�as, Jaime L.; Opitz, John M.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 11 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0148-7299
- DOI
- 10.1002/(sici)1096-8628(19980401)76:4<291::aid-ajmg3>3.0.co;2-t
No coin nor oath required. For personal study only.
✦ Synopsis
Field theory provides a rational basis for birth defects terminology. During blastogenesis in higher metazoa, pattern formation in the primary field leads to the establishment of upstream expression domains of growth and transcription factors, which, in various permutations and at specific sites and times, lay down the pattern of progenitor fields. Further spatially coordinated, temporally synchronized, and epimorphically hierarchical morphogenetic events, mostly during organogenesis, lead to the attainment of final form in the secondary, epimorphic fields. Because of shared molecular determinants, spatial contiguity, and close timing of morphogenetic events during blastogenesis, most malformations arising during blastogenesis are polytopic, i.e., involving two or more progenitor fields, e.g., acrorenal, cardiomelic, gastromelic, or splenomelic anomalies. Defects of organogenesis tend to be monotopic malformations, e.g., cleft palate or postaxial polydactyly. We suggest that what were called "associations" (e.g., VATER, schisis) be designated primary polytopic developmental field defects, or simply polytopic field defects, and that the term "association" be reserved for the original definition of a statistical combination of anomalies (mostly of organogenesis) [Spranger et al. (1982): J Pediatr 100:160-165]. If genetically caused or predisposed, all structures involved in a polytopic or monotopic malformation are genetically abnormal, whereas the parts secondarily affected as a consequence of a malformation sequence (e.g., spina bifida) are genetically normal. Polytopic field anomalies, per se, must be distinguished from pleiotropy, although such anomalies may constitute a part of pleiotropy (e.g., in trisomy 18). Because they are downstream from pattern-forming events in the primary field, multiple anomalies of organogenesis more likely represent syndromal pleiotropy.
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