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The study was conducted to plan for a community-health campaign to inform working-class Filipinos about the causes and prevention of orofacial clefting. Prenatal micronutrients may play a role in preventing orofacial clefting. Therefore, women's practices and perspectives on barriers to and facilitators of micronutrient supplementation were elicited. A total of 43 women and 22 health care workers were interviewed. Barriers to taking supplements included side effects, late prenatal care, the view that micronutrients are medications, inadequate supply, and health care workers who were unaware that prenatal vitamin supplements prevent congenital anomalies. The main facilitator was women's understanding that prenatal micronutrients improve the physical well-being of both mother and child. Given that women view having healthy babies as a reason to take micronutrients and that the health care workers lacked knowledge related to the use of micronutrients to prevent congenital anomalies, uptake of prenatal micronutrient supplementation programs may improve by specifically promoting the health benefit of preventing congenital anomalies.

Objective: The objective of this study was to use array comparative genomic hybridization to detect causal microdeletions in samples of subjects with cleft lip and palate., Subjects: We analyzed DNA samples from a male patient and his parents seen during surgical screening for an Operation Smile medical mission in the Philippines., Method: We used Affymetrix® Genome-Wide Human SNP Array 6.0 followed by sequencing and quantitative polymerase chain reaction using SYBR Green I dye., Results: We report the second case of 3q29 microdeletion syndrome including cleft lip with or without cleft palate and the first case of this microdeletion syndrome inherited from a phenotypically normal mosaic parent., Conclusions: Our findings confirm the usefulness of a comparative genomic hybridization to detect causal microdeletions and indicate that parental somatic mosaicism should be considered in healthy parents for genetic counseling of the families. We discuss important ethical implications of sharing health impact results from research studies with the participant families.

Objective: To describe beliefs about the cause, prevention, and treatment of cleft lip with or without cleft palate (CL+/-P) among working class people and health care workers in the Philippines., Design and Setting: The study was a focused ethnography and took place in the province of Negros Occidental, Philippines., Participants: Using a stratified purposeful recruitment strategy, 80 individuals were selected for study. They were categorized into three groups: those having a CL+/-P or a child with a CL+/-P, those who neither had a CL+/-P nor child with CL+/-P, and health care workers., Methods: Kleinman's explanatory models of illness theory were used to elicit Filipino explanations for CL+/-P. Data were collected through guided individual and group informant interviews and analyzed through content analysis., Results: Filipinos reported that inheritance, falls, cravings, environmental factors, and God's will were causes for CL+/-P. Beliefs about prevention of CL+/-P included limiting the number of children, being careful not to fall, and avoiding environmental factors. It was found that general causal explanations for CL+/-P were not always congruent with personal causal explanations, and general/personal causal explanations for CL+/-P were not always congruent with prevention explanations., Conclusion: By eliciting patients' explanations for CL+/-P and comparing these with their own, clinicians can find commonalities between divergent explanations and use these as a starting point from which to improve health outcomes. Findings from this study will be used to guide the design of health campaigns regarding CL+/-P in the Philippines.

Isolated or nonsyndromic cleft lip and palate (NS CLP) is a complex disorder resulting from multiple genetic and environmental factors. NS CLP has a birth prevalence of 1 per 500 in the Philippines where large families provide an opportunity for gene localization. Genotyping of 392 microsatellite repeat markers at 10 cM intervals over the genome was performed by the Center for Inherited Disease Research (CIDR) on 220 Filipino families with 567 affected and 1,109 unaffected family members genotyped. Among the most statistically significant results from analysis of the genome-wide scan data was a 20 cM region at 8p11-23 in which markers had LODs > or =1.0. This region on 8p11-23 has not been found in any previous genome wide scan nor does it contain any of the candidate genes widely studied in CLP. Fine mapping in 8p11-23 was done in the 220 families plus an additional 51 families, using SNP markers from 10 known genes (FGFR1, NRG1, FZD3, SLC8A1, PPP3CC, EPHX2, BNIP3L, EGR3, PPP2R2A, and NAT1) within the 20 cM region of 8p11-23. Linkage and association analyses of these SNPs yield suggestive results for markers in FGFR1 (recessive multipoint HLOD 1.07) and BAG4 (recessive multipoint HLOD 1.31)., (Copyright 2007 Wiley-Liss, Inc.)

Objective: To investigate dermatoglyphic patterns in 95 nonsyndromic Filipino subjects with nonsyndromic cleft lip with or without cleft palate (CL/P) and 90 of their unaffected relatives., Design: Retrospective study of dermatoglyphic pattern types., Setting: Negros Occidental and Cavite in the Philippines., Participants: Nonsyndromic subjects with CL/P and their unaffected relatives., Methods: Dermatoglyphic patterns were categorized as arch, ulnar loop, radial loop, whorl, or other by three independent raters. Pattern data from the subjects, the unaffected relatives, and an unaffected control population (from the literature) were compared using chi-square tests. As a measure of asymmetry, dissimilarity between pattern types on homologous fingers was quantified and compared using Student's t tests., Results: The frequency of arches (p = .016) and ulnar loops (p = .04) were significantly increased, and whorls decreased in the affected group (p = .0015), compared with the unaffected group. Affected female subjects had significantly more ulnar loops and arches (p = .009 and p = .023, respectively) and fewer whorls (p < .0001) than the unaffected female subjects. There were no significant differences between affected and unaffected male subjects. Dissimilarity scores were significantly different between male and female subjects and between subjects with CL/P and unaffected relatives. Additionally, pattern type frequencies for the relatives fell in between the frequencies for the CL/P group and the controls., Conclusions: In this Filipino population, differences in frequency of dermatoglyphic pattern types and pattern dissimilarity exist between individuals with orofacial clefts and their unaffected relatives and between both groups and controls, with the major effect seen in female subjects.

Cleft lip with or without cleft palate (CL/P) is a common birth defect (birth prevalence ranging from 1/500 to 1/2,000) with a complex etiology. Traits potentially related to CL/P, such as dermatoglyphics, may reflect the genetic and epidemiologic heterogeneity observed in CL/P. Such phenotypic heterogeneity in dermatoglyphic patterns may account for some of the variability in previously reported associations of dermatoglyphics and CL/P. To test this hypothesis, we took dermatoglyphic prints from individuals with nonsyndromic CL/P (n = 460) and their unaffected relatives (n = 254) from the Philippines and China. For both samples three raters designated the patterns as arch, ulnar loop, radial loop, whorl, or "other." Chi-square analysis and standard ANOVA were used to investigate heterogeneity between Filipino and Chinese study subjects. The significant associations between particular pattern types and CL/P were not the same in both populations, demonstrating population-specific association of CL/P and dermatoglyphic pattern types. The ANOVA of pattern type included both CL/P cases and their relatives, with affection status, sex, and population group as variables. For each pattern type except arches, population was significant (p < 0.0001); for radial loops, affection status was additionally significant (p < 0.0001). When only CL/P cases were considered, population was again significant for the ulnar loop (p < 0.0001), whorl (p < 0.0001), and "other" (p = 0.0002) patterns. The ANOVAs demonstrate between-population heterogeneity in dermatoglyphic pattern types. These results support our hypothesis that population-specific associations and population heterogeneity in dermatoglyphic patterns exist for CL/P cases and their relatives.

Background: Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain., Methods: Associations between maternal vitamin B-6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case-control studies at two sites in the Philippines--Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts., Results: The risk of having a CL/P-affected child increased with increasing tertile of vitamin B-6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI, 2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94-2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90; OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B-6, and case-control status that produced different results in study areas of higher versus lower prevalence of vitamin B-6 deficiency., Conclusions: Poor maternal vitamin B-6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate-CL/P associations were inconsistent and may be related to the vitamin B-6 status or other characteristics of the populations under study.

Cleft lip with or without cleft palate (CL/P) is a congenital anomaly with variable birth prevalence based on geographic origins, with the highest rates commonly found in Asian populations. About 70% of cases are nonsyndromic (NS), in which the affected individual has no other abnormalities. NS CL/P is a complex disorder with genetic and environmental effects and no specific genetic loci yet confirmed. Fifteen candidate regions were examined for linkage to NS CL/P. Regions were chosen based on previous suggestive linkage and/or association in human families, or suggestive animal model data. Polymorphic markers in these regions were genotyped for analysis on 36 Filipino families comprised of 126 affected and 218 unaffected individuals. An additional 70 families with 149 affecteds were used for replication of suggestive results. Parametric (LOD score) and nonparametric (SIMIBD) linkage analyses were performed as well as transmission disequilibrium test (TDT) analysis. Five markers yielded suggestive results from the 36 families. The parametric LOD scores for the MSX1-CA and D4S1629 were >1.0 and the SIMIBD P values for D6S1029 and RFC1 are suggestive (<0.06), while the SIMIBD P value of 0.01 for TGFA was significant. Since the Msx1 mouse knockout has cleft palate and MSX1 mutations have been found in rare cases of syndromic CL/P, this locus is especially plausible for linkage. Previous studies have also found linkage of NS CL/P to 4q31 and 6p23. These regions contain several candidate genes, including AP2 at 6p23 and FGF2, BMPR1B, and MADH1 at 4q31. TGFA has both linkage and linkage disequilibrium data supporting it as a candidate gene for NS CL/P. While no region was definitively confirmed for linkage to NS CL/P, the data do support further investigation using larger sample sizes and candidate gene studies at 2p13.2, 4p16.2, 4q31, 6p23, and 16q22-24., (Copyright 2003 Wiley-Liss, Inc.)

Clinical and epidemiologic studies of defined geographic populations can serve as a means of establishing data important for genetic counseling and as a first step in identifying strategies best suited for identification of causes. Under the sponsorship of Operation Smile International, clinical, genetic, and epidemiologic studies were carried out at six sites within the Philippines between 1989 and 1996. Patients who were being evaluated for surgical repair of craniofacial anomalies (primarily clefts of the lip and palate) were briefly examined for the presence of associated anomalies, and a family history was obtained to look for the frequency of cleft lip and palate in siblings. Birth records of 47,969 newborns over an 8-year period at one hospital in Bacolod City in the province of Negros Occidental were reviewed. Medical records of infants born with clefts of the lip and/or palate and other major anomalies were reviewed and birth prevalence rates calculated. Findings include a birth prevalence of 1.94 per 1000 live births for cleft lip with/without palate in the Philippines. Recurrence rates in siblings for nonsyndromic clefts of the lip and palate were 23 per 1000 for cleft lip with or without cleft palate, and 14 per 1000 for cleft palate only. The percentage of clefts associated with multiple anomalies was 21% at birth and 6% for individuals examined during the screening process, providing evidence for a high postnatal death rate. These data provide groundwork for additional etiologic studies including segregation analysis and molecular genetic studies involving linkage or association, as well as for studies of environmental contributions to clefting such as vitamin deficiencies. Preliminary molecular analysis using an association approach is reported in a companion paper. The findings suggest a high incidence of cleft lip and palate in native-born Filipinos.