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Approach to congenital malformations

Carlos A Bacino, MD, FACMG
Section Editor
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Elizabeth TePas, MD, MS


Major congenital malformations occur in approximately 3 to 4 percent of livebirths, although minor anomalies are more frequent. Birth defects can be isolated or present in a characteristic combination or pattern.


In ancient times, birth defects were believed to result from the action of supernatural forces [1]. They were viewed as manifestations of evil and sometimes as signs of God's warnings for impending disasters. Even though the perception of birth defects differs from culture to culture, it has been attributed mostly to negative forces. These concepts have evolved from ancient times until the present, although superstitions persist in many cultures.

A more systematic study of birth defects began in the mid-20th century. This coincided with the recognition of the teratogenic effects of exposures to rubella infections and thalidomide during pregnancy.

The term "dysmorphology" was coined in the 1960s to define the study of abnormal features. This term is used to encompass the variability of normal physical traits, as well as pathologic features resulting from abnormal development. An individual with unusual physical features is said to be dysmorphic. Experts in dysmorphology are trained to describe patterns of abnormal traits and establish a diagnostic hypothesis based upon their appearance.


Specific terms are used to describe congenital abnormalities. The terms indicate how the anomalies were caused (table 1).


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Literature review current through: Sep 2016. | This topic last updated: Jun 16, 2014.
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  1. Human malformations and related anomalies. In: Oxford monographs on medical genetics, Stevenson RE, Hall JG, Goodman RM (Eds), Oxford University Press, New York 1993. Vol 1.
  2. Muragaki Y, Mundlos S, Upton J, Olsen BR. Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. Science 1996; 272:548.
  3. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med 1985; 313:837.
  4. Queisser-Luft A, Stolz G, Wiesel A, et al. Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998). Arch Gynecol Obstet 2002; 266:163.
  6. Myrianthopoulos NC, Chung CS. Congenital malformations in singletons: epidemiologic survey. Report from the Collaborative Perinatal project. Birth Defects Orig Artic Ser 1974; 10:1.
  7. Leppig KA, Werler MM, Cann CI, et al. Predictive value of minor anomalies. I. Association with major malformations. J Pediatr 1987; 110:531.
  8. Méhes K, Mestyán J, Knoch V, Vincellér M. Minor malformations in the neonate. Helv Paediatr Acta 1973; 28:477.
  9. Graham JM. Clinical approach to deformation problems. In: Smith's recognizable patterns of human deformation, Elsevier Saunders, Philadelphia 2007. p.3.
  10. Horton WA, Lunstrum GP. Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism. Rev Endocr Metab Disord 2002; 3:381.
  11. Aicardi J, Chevrie JJ, Rousselie F. [Spasma-in-flexion syndrome, callosal agenesis, chorioretinal abnormalities]. Arch Fr Pediatr 1969; 26:1103.
  12. Tonkin ET, Wang TJ, Lisgo S, et al. NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome. Nat Genet 2004; 36:636.
  13. Jones KL. Dysmorphology approach and classification. In: Smith's recognizable patterns of human malformation, 6th ed, Elsevier Saunders, Philadelphia 2006. p.1.
  14. POTTER EL. Bilateral renal agenesis. J Pediatr 1946; 29:68.
  15. Thomas IT, Smith DW. Oligohydramnios, cause of the nonrenal features of Potter's syndrome, including pulmonary hypoplasia. J Pediatr 1974; 84:811.
  16. Opitz JM, Herrmann J, Pettersen JC, et al. Terminological, diagnostic, nosological, and anatomical-developmental aspects of developmental defects in man. Adv Hum Genet 1979; 9:71.
  17. Hersh JH, Angle B, Fox TL, et al. Developmental field defects: coming together of associations and sequences during blastogenesis. Am J Med Genet 2002; 110:320.
  18. Temtamy SA, Miller JD. Extending the scope of the VATER association: definition of the VATER syndrome. J Pediatr 1974; 85:345.
  19. Nelson K, Holmes LB. Malformations due to presumed spontaneous mutations in newborn infants. N Engl J Med 1989; 320:19.
  20. Milunsky A, Ulcickas M, Rothman KJ, et al. Maternal heat exposure and neural tube defects. JAMA 1992; 268:882.
  21. Chambers CD, Johnson KA, Dick LM, et al. Maternal fever and birth outcome: a prospective study. Teratology 1998; 58:251.
  22. Pleet H, Graham JM Jr, Smith DW. Central nervous system and facial defects associated with maternal hyperthermia at four to 14 weeks' gestation. Pediatrics 1981; 67:785.
  23. Mattson SN, Schoenfeld AM, Riley EP. Teratogenic effects of alcohol on brain and behavior. Alcohol Res Health 2001; 25:185.
  24. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000; 343:1608.
  25. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001; 153:961.
  26. Hanson N, Leachman S. Safety issues in isotretinoin therapy. Semin Cutan Med Surg 2001; 20:166.
  27. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med 1998; 338:1128.
  28. Petersen EE, Mitchell AA, Carey JC, et al. Maternal exposure to statins and risk for birth defects: a case-series approach. Am J Med Genet A 2008; 146A:2701.
  29. Taguchi N, Rubin ET, Hosokawa A, et al. Prenatal exposure to HMG-CoA reductase inhibitors: effects on fetal and neonatal outcomes. Reprod Toxicol 2008; 26:175.
  30. Hall J, Froster-Iskenius UG, Allanson JE. Handbook of normal physical measurements, 1st ed, Oxford Medical Publications, Oxford University Press, 1989.
  31. Cheung SW, Shaw CA, Yu W, et al. Development and validation of a CGH microarray for clinical cytogenetic diagnosis. Genet Med 2005; 7:422.
  32. Yobb TM, Somerville MJ, Willatt L, et al. Microduplication and triplication of 22q11.2: a highly variable syndrome. Am J Hum Genet 2005; 76:865.
  33. Shaffer LG, Kashork CD, Saleki R, et al. Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. J Pediatr 2006; 149:98.
  34. Schoumans J, Ruivenkamp C, Holmberg E, et al. Detection of chromosomal imbalances in children with idiopathic mental retardation by array based comparative genomic hybridisation (array-CGH). J Med Genet 2005; 42:699.
  35. Tyson C, Harvard C, Locker R, et al. Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH. Am J Med Genet A 2005; 139:173.
  36. Stankiewicz P, Beaudet AL. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr Opin Genet Dev 2007; 17:182.
  37. Lu X, Shaw CA, Patel A, et al. Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS One 2007; 2:e327.