Cleft Lip Differences Vary Among Different Populations

One interesting study is called, Segregation analysis of cleft lip with or without cleft palate: a comparison of Danish and Japanese data. By C S Chung, D Bixler, T Watanabe, H Koguchi, and P Fogh-Andersen - Am J Hum Genet. 1986 November; 39(5): 603611. Here is an excerpt: Abstract - The genetic basis of cleft lip with or without cleft palate [CL(P)] remains unresolved. The controversy on the role of a major gene is confounded with possible population differences. This study examines the issue of population differences by comparing two contrasting populations: Caucasians and Japanese. Japanese are known to have higher population incidence of CL(P) and yet lower recurrence risks among relatives. The study subjects consist of 2,998 nuclear families of the Danish population and 627 families of the Japanese population. The uniformly coded data were subjected to complex segregation analysis based on the mixed model. The analysis has revealed that the Danish data can be best explained by a combination of major gene action and multifactorial inheritance. The best-fitting model is characterized by recessive gene with displacement effect (t) of 2.7 in the standardized unit and gene frequency of .035. The heritability is estimated as .97. The transmission probability of for the major gene is consistent with 1/2. On the contrary, the Japanese data can be best accounted for only by multifactorial inheritance with the heritability estimate of .77. No major heterogeneity could be detected between subsets of the data within the populations as grouped by types of ascertainment or mating. It is thus concluded that the observed inconsistency between the two populations is explained by a significant role of major gene in the Caucasian population, but not in the Japanese population.

Another interesting study is called, A Preliminary Study of Facial Growth and Morphology in Unoperated Male Unilateral Cleft Lip and Palate Subjects Over 13 Years of Age by Michael Mars, F.D.S., D.Orth. and William J. B. Houston, F.D.S., Ph.D. Michael Mars and William J. B. Houston (1990) The Cleft Palate-Craniofacial Journal: January 1990, Vol. 27, No. 1, pp. 7-10. Here is an excerpt: Abstract - This paper investigates the effects of surgery on facial growth and morphology in Sri Lankan males with unilateral cleft lip and palate who were over 13 years of age at the time of study with cephalometry and dental study models. Three separate subgroups were analyzed: those who had totally unrepaired cleft lip and palate, those who received lip repair in infancy but not palatal repair, and those who had lip and palate repair in infancy. Twenty-three healthy noncleft Sri Lankan males over 13 years formed a control group from the same racial background. The results show that subjects who had no surgery had a potential for normal maxillary growth. Subjects who have had lip repair in early infancy show relatively normal maxillary growth, but maxillary hypoplasia is common when the palate has also been repaired early.

Another interesting study is called, Identification of susceptibility loci for nonsyndromic cleft lip with or without cleft palate in a two stage genome scan of affected sib-pairs by N.J. Prescott, M.M. Lees, R.M. Winter and S. Malcolm - Human Genetics Volume 106, Number 3, 345-350. Here is an excerpt: Abstract - Nonsyndromic cleft lip with or without cleft palate (CL/P) is a complex disorder of multigenic origin involving between two and ten loci. Linkage and association studies of CL/P have implicated a number of candidate genes and regions but have often proved difficult to replicate. Here, we report the findings from a two-stage genome-wide scan of 92 affected sib-pairs to identify susceptibility loci to CL/P. An initial set of 400 microsatellite markers was used, with an average spacing of 10 cM throughout the genome. Eleven regions on eight chromosomes were found to have a P-value smaller than 0.05. These eight chromosomes were then further mapped with a second set of markers to increase the average map density to 5 cM. In seven out of eleven areas densely mapped, significance was markedly increased by decreasing the marker interval. Excessive allele sharing was found at 1p (NPL=2.35, P=0.009, MLS=1.51), 2p (NPL=1.77, P=0.04, MLS=0.66), 6p (NPL=2.35, P=0.009, MLS=1.34), 8q (NPL=2.15, P=0.015, MLS=1.51) 11cen (NPL=2.70, P=0.003, MLS=2.10), 12q (NPL=2.08, P=0.02, MLS=1.5), 16p (NPL=2.1, P=0.018, MLS=0.97) and Xcen-q (NPL=2.40, P=0.008, MLS=2.68). Although none reached the level required for significant susceptibility loci, two of these areas have previously been implicated in CL/P, viz. 2p13, an area harbouring the TGFA gene, and 6p23-24. We also demonstrate highly suggestive linkage to a susceptibility locus for nonsyndromic clefting on the X chromosome. Further studies are currently underway to replicate these findings in a larger cohort of affected sib-pairs.

We all owe a debt of gratitude to these researchers for their fine work and dedication. For more information, please read the studies in their entirety.