Review of the role of potential teratogens in the origin of human nonsyndromic oral clefts

Abstract

Oral clefts are common birth defects affecting approximately 1 every 1,000 caucasian newborns. While many syndromes with cleft lip with or without cleft palate (CL/P) or with cleft palate (CP) are recognized, the majority of oral clefts fall into the category of “nonsyndromic oral clefts” and the etiology of this group remains incompletely understood. Investigators agree that oral clefts are multifactorial in origin, with both genetic and environmental factors in their etiology. While animal models have identified several teratogens for oral clefts, their precise relevance for humans remains unclear. The goal of this work is to review literature on environmental exposures potentially associated with non‐syndromic oral clefts. © 1996 Wiley‐Liss, Inc.

Correlation of susceptibility to 6-aminonicotinamide and hydrocortisone-induced cleft palate

“…Family and twin studies have demonstrated that inherited susceptibility is the most important determinant of risk (Murray, 2002;Prescott et al, 2001), but genome-wide linkage analyses show that heritability is based on multiple genes of moderate effect rather than any single major loci (Marazita et al, 2003). The environment also plays an important role in human orofacial clefting, and several teratogens have been identified as risk factors (Wyszynski and Beaty, 1996).…”

Increased rate of major malformations in offspring exposed to valproate during pregnancy

“…18 Other congenital malformations associated with this exposure have included heart defects, oral clefts, genital abnormalities, and limb defects. 10,[19][20][21][22][23][24][25] We have performed a prospective study of the rate of occurrence of major malformations identified at birth in infants whose mothers had taken valproate as monotherapy and had enrolled in the North American Antiepileptic Drug (AED) Pregnancy Registry.…”

Maternal Obesity and the Risk for Orofacial Clefts in the Offspring

“…The etiology is suggested to be multifactorial, involving both genetic and environmental factors. Among nongenetic risk factors that have been mentioned are maternal smoking, use of certain drugs like some anticonvulsants and corticosteroids, organic solvent exposure, and folic acid deficiency (Wyszynski and Beaty, 1996;Wyszynski et al, 1997). In Sweden maternal drug use during pregnancy apparently plays a minor role (Källén, 2003).…”