Multiple Congenital Malformations

Malformation Population Incidence (per 1000)Cleft lip with or without cleft palate 0.4-1.7

Cleft palate 0.4

Congenital dislocation of hip 2*

Congenital heart defects 4-8

Ventricular septal defect 1.7

Patent ductus arteriosus 0.5

Atrial septal defect 1.0

Aortic stenosis 0.5

Neural tube defects 2-10

Spina bifida and anencephaly Variable

Pyloric stenosis 1†, 5*

Table 8‐8. Some Common Congenital Malformations with Multifactorial Inheritance

*Per 1000 males.†Per 1000 females.Note: Population incidence is approximate. Many of these disorders are heterogeneous and are usually but not invariably multifactorial.Data from Carter CO: Genetics of common single malformations. Br Med Bull 32:21‐26, 1976; Nora JJ: Multifactorial inheritance hypothesis for the etiology of congenital heart diseases: the genetic environmental interaction. Circulation 38:604‐617, 1968; and Lin AE, Garver KL: Genetic counseling for congenital heart defects. J Pediatr 113:1105‐1109, 1988. 

Figure 9.3 Hypothetical liability curves in the general population and in relatives for a hereditary disorder in which the genetic predisposition is multifactorial.

Anencephaly, Spina Bifida Encephalocele and Iniencephaly

Neural Tube Defects

Figure 8-8. The origin of the neural tube defects anencephaly and spina bifida.

(From Jones KL: Smith's Recognizable Patterns of Human Malformation, 4th ed. Philadelphia, WB Saunders, 1988.)

Multisite Closure

Neural Tube Defects

• Defects in closure of the anterior neural tube.

• 1% incidence in Ireland.

• 0.2% or less in the USA.

• Chromosome disorders, single gene disorders, teratogens amniotic bands account for small %.

• MOST ARE ISOLATED!!!!

• Most have multifactorial causation

Cleft Lip and Palate 

Clubfoot

Gastroschisis

Omphalocele

Amniotic Band