An assessment of orofacial clefts in Tanzania

<p>Abstract</p> <p>Background</p> <p>Clefts of the lip (CL), the palate (CP), or both (CLP) are the most common orofacial congenital malformations found among live births, accounting for 65% of all head and neck anomalies. The frequency and pattern of orofacial clefts in different parts of the world and among different human groups varies widely. Generally, populations of Asian or Native American origin have the highest prevalence, while Caucasian populations show intermediate prevalence and African populations the lowest. To date, little is known regarding the epidemiology and pattern of orofacial clefts in Tanzania.</p> <p>Methods</p> <p>A retrospective descriptive study was conducted at Bugando Medical Centre to identify all children with orofacial clefts that attended or were treated during a period of five years. Cleft lip and/or palate records were obtained from patient files in the Hospital's Departments of Surgery, Paediatrics and medical records. Age at presentation, sex, region of origin, type and laterality of the cleft were recorded. In addition, presence of associated congenital anomalies or syndromes was recorded.</p> <p>Results</p> <p>A total of 240 orofacial cleft cases were seen during this period. Isolated cleft lip was the most common cleft type followed closely by cleft lip and palate (CLP). This is a departure from the pattern of clefting reported for Caucasian and Asian populations, where CLP or isolated cleft palate is the most common type. The distribution of clefts by side showed a statistically significant preponderance of the left side (43.7%) (χ²= 92.4, p < 0.001), followed by the right (28.8%) and bilateral sides (18.3%). Patients with isolated cleft palate presented at very early age (mean age 1.00 years, SE 0.56). Associated congenital anomalies were observed in 2.8% of all patients with orofacial clefts, and included neural tube defects, Talipes and persistent ductus arteriosus.</p> <p>Conclusions</p> <p>Unilateral orofacial clefts were significantly more common than bilateral clefts; with the left side being the most common affected side. Most of the other findings did not show marked differences with orofacial cleft distributions in other African populations.</p

Genomewide Association Study of African Children Identifies Association of <i>SCHIP1</i> and <i>PDE8A</i> with Facial Size and Shape

<div><p>The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes <i>SCHIP1</i> and <i>PDE8A</i> were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both <i>SCHIP1</i> and <i>PDE8A</i>, we demonstrated clear expression in the developing mouse face by both whole-mount <i>in situ</i> hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.</p></div

<i>SCHIP1</i> locus associated with centroid size.

<p><b>(A)</b> Regional association plot of centroid size at the <i>SCHIP1</i> locus. Association data are shown using GWAS P-values with the meta-analysis P-value for the lead SNP, rs79909949. The LD pattern is based on the 1000 Genomes Project 2012 African reference and GRCh37/hg19. The estimated recombination rate (cM/Mb) is from HapMap samples. <b>(B)</b> Relative facial size at the upper and lower 95% confidence intervals for centroid size after adjusting for sex and age.</p

GWAS, replication, and meta-analysis results of replicated association signals.

<p>GWAS, replication, and meta-analysis results of replicated association signals.</p

Facial size and shape phenotypes tested for genetic association.

<p>Facial size and shape phenotypes tested for genetic association.</p

Expression of <i>Schip1</i> and <i>Pde8a</i> during mouse embryonic development.

<p>Whole-mount <i>in situ</i> hybridization of <b>(A-D)</b> <i>Schip1</i> and <b>(E-H)</b> <i>Pde8a</i> expression in mouse embryos from E9.5 to E12.5. ba1, first branchial arch (future mandible); ba2, second branchial arch; fb, forebrain; fn, frontonasal process; fl, forelimb; hb, hindbrain; hl, hindlimb; ln, lateronasal process; mb, midbrain; md, mandible; mn, medionasal process; mx, maxilla; ov, otic vesicle.</p

3D Facial scan with annotated landmarks.

<p>3D facial mesh obtained for each study individual with study landmarks obtained from automatic landmarking overlaid and labeled.</p

World Health Organization 2007 reference BMI Z-scores for the Tanzanian study population.

<p>Histogram of Tanzanian Z-scores calculated from WHO 2007 reference data by age and sex with WHO cutoffs for thinness and overweight classifications.</p