Biomedical subjects

Seth M Weinberg

Publications and source records attributed to Seth M Weinberg.

At least 19 recordsLinked to original sources

PubMed2026

Trio-based GWAS reveals loci associated with different forms of isolated cleft lip.

Orofacial clefts (OFCs) are the most common craniofacial birth defect and comprise a diverse group of traits with complex and heterogeneous etiologies. Genetic studies of OFCs typically approach this diversity by stratifying cases into broad diagnostic classes, including cleft lip (CL), cleft palate (CP), and cleft lip with palate (CLP). Although this strategy has yielded important insights into OFC risk, it ignores the phenotypic heterogeneity within each subtype. CL exhibits marked phenotypic variability, involving differences in alveolar involvement, laterality, and sidedness that may reflect distinct etiologies. Given this phenotypic diversity within CL, we assembled a multi-ancestry cohort of 837 nonsyndromic CL case-parent trios with whole-genome sequencing and detailed phenotyping. We performed genome-wide association scans (GWAS) via transmission disequilibrium tests for CL overall and for 14 CL subtypes defined by involvement of the alveolus (with and without), laterality (uni- and bilateral), and sidedness (left and right). We identified four genome-wide significant loci. Two loci, IRF6 and 8q24.21, were both detected in the overall CL GWAS. PLCB1/PLCB4 and MAFB were detected in GWASs of alveolar cleft involvement and CL left sidedness, respectively. These subtype-specific associations were followed by case-only comparisons that reflect the presence or absence of alveolus cleft or left-sided bias of CL to confirm the specificity of the association signal to the particular subtype. Our results provide evidence of within-class CL subtype-specific genetic links for loci previously discussed in the context of primary OFC classes and demonstrate the value of granular OFC subtype characterization to capture trait-specific associations.

Alveolus Cleft↗

PubMed2026

Shared genetic basis and structure of syndromic and normal facial variation.

The question of how gene mutations of large effect and common variants of small effect relate to phenotypic variation dates from the origins of genetics. Mendelian diseases result from rare germline variants with major effects, while complex traits are associated with multiple, mostly common variants of small effect. High-dimensional phenotypes, such as facial shape, can shed new light on this age-old dichotomy, as their variation can be characterized in terms of directions in multivariate morphospace. Within such spaces, do Mendelian disease mutations move phenotypes along the same directions as common variants, or do they forge new directions that diverge from the common structure of background variation? Here, we analyze facial shape variation for 66 syndromes, quantify multivariate axes of facial shape variation for each syndrome, and test whether common genetic variants in cohorts of non-syndromic subjects are associated with phenotypic position along these same axes. We find that syndromic facial shape generally follows the background variance-covariance structure of facial shape in the general population. Furthermore, syndromic probands' unaffected relatives have subtle facial morphology resembling the syndromes of their affected relatives. These results suggest that Mendelian disease variants act on facial shape in ways similar to common variants. Syndromic probands with higher "severity" likely occur on genetic backgrounds with higher cumulative severity of common variants for each syndromic axis. These findings position Mendelian diseases at extremes along phenotypic continua that exist in the background population rather than as qualitatively different phenotypes distinct from the overall structure of normal human phenotypic variation.

Humans↗

PubMed2026

Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease.

BACKGROUND: Orofacial clefts (OFCs) and other palate abnormalities (PAs) are among the most common birth defects worldwide and are characterized by the abnormal formation of the lip and/or palate. Genetic studies have traditionally classified OFC cases as either syndromic, involving OFCs alongside other congenital anomalies, or nonsyndromic, which represent the majority of cases and occur in isolation. Emerging genomic evidence indicates that genes traditionally associated with syndromic forms of OFC can also harbor variants contributing to isolated cases, challenging the notion of a strict dichotomy between these categories and supporting their integration for gene discovery. METHODS: In this study, we applied multiple analytic approaches to characterize the genetic architecture of OFC and PAs by integrating genomic data from 2,497 trios with probands diagnosed with an OFC (n=2,080) or PA (n=417). We compared these findings across OFC subtypes and syndromic status with those from 5,515 control trios to identify enriched biological pathways and mechanisms and to prioritize candidate genes using variant burden testing. RESULTS: We observed a significant enrichment of de novo protein-truncating and damaging missense variants in cases compared to controls (OR = 2.17, p = 1.21×10-32), with particularly strong signals in biologically relevant gene sets involving OFC-associated, constrained, Mendelian disorder, and mouse candidate genes. Variant burden testing identified 39 OFC risk genes at FDR ≤ 0.05, which we then integrated with 593 established OFC genes to interrogate the functional underpinnings of OFC via network analysis. This analysis revealed 309 high-order interactor genes not previously associated with OFC. Notably, this OFC network clustered into ten distinct biological pathways, with nucleosome-associated genes showing significant enrichment among cases in our cohort (OR = 14.8, p = 8.1×10-4). In a final integrative step, we combined evidence across all analyses to nominate 231 candidate genes, 32 of which contained at least two deleterious de novo variants in our cohort. CONCLUSIONS: These findings underscore the value of integrating diverse OFC and PA subtypes, syndromic status, and variant classes to elucidate the genetic architecture of these disorders, highlighting both phenotypic expansion of known disease genes and the emergence of novel gene-phenotype associations.

De Novo Variant Enrichment↗

PubMed2025

Clustering individuals using INMTD: a novel versatile multi-view embedding framework integrating omics and imaging data.

MOTIVATION: Combining omics and images can lead to a more comprehensive clustering of individuals than classic single-view approaches. Among the various approaches for multi-view clustering, nonnegative matrix tri-factorization (NMTF) and nonnegative Tucker decomposition (NTD) are advantageous in learning low-rank embeddings with promising interpretability. Besides, there is a need to handle unwanted drivers of clusterings (i.e. confounders). RESULTS: In this work, we introduce a novel multi-view clustering method based on NMTF and NTD, named INMTD, which integrates omics and 3D imaging data to derive unconfounded subgroups of individuals. According to the adjusted Rand index, INMTD outperformed other clustering methods on a synthetic dataset with known clusters. In the application to real-life facial-genomic data, INMTD generated biologically relevant embeddings for individuals, genetics, and facial morphology. By removing confounded embedding vectors, we derived an unconfounded clustering with better internal and external quality; the genetic and facial annotations of each derived subgroup highlighted distinctive characteristics. In conclusion, INMTD can effectively integrate omics data and 3D images for unconfounded clustering with biologically meaningful interpretation. AVAILABILITY AND IMPLEMENTATION: INMTD is freely available at https://github.com/ZuqiLi/INMTD.

Cluster Analysis↗

PubMed2025

Optimized phenotyping of complex morphological traits: enhancing discovery of common and rare genetic variants.

Genotype-phenotype (G-P) analyses for complex morphological traits typically utilize simple, predetermined anatomical measures or features derived via unsupervised dimension reduction techniques (e.g. principal component analysis (PCA) or eigen-shapes). Despite the popularity of these approaches, they do not necessarily reveal axes of phenotypic variation that are genetically relevant. Therefore, we introduce a framework to optimize phenotyping for G-P analyses, such as genome-wide association studies (GWAS) of common variants or rare variant association studies (RVAS) of rare variants. Our strategy is two-fold: (i) we construct a multidimensional feature space spanning a wide range of phenotypic variation, and (ii) within this feature space, we use an optimization algorithm to search for directions or feature combinations that are genetically enriched. To test our approach, we examine human facial shape in the context of GWAS and RVAS. In GWAS, we optimize for phenotypes exhibiting high heritability, estimated from either family data or genomic relatedness measured in unrelated individuals. In RVAS, we optimize for the skewness of phenotype distributions, aiming to detect commingled distributions that suggest single or few genomic loci with major effects. We compare our approach with eigen-shapes as baseline in GWAS involving 8246 individuals of European ancestry and in gene-based tests of rare variants with a subset of 1906 individuals. After applying linkage disequilibrium score regression to our GWAS results, heritability-enriched phenotypes yielded the highest SNP heritability, followed by eigen-shapes, while commingling-based traits displayed the lowest SNP heritability. Heritability-enriched phenotypes also exhibited higher discovery rates, identifying the same number of independent genomic loci as eigen-shapes with a smaller effective number of traits. For RVAS, commingling-based traits resulted in more genes passing the exome-wide significance threshold than eigen-shapes, while heritability-enriched phenotypes lead to only a few associations. Overall, our results demonstrate that optimized phenotyping allows for the extraction of genetically relevant traits that can specifically enhance discovery efforts of common and rare variants, as evidenced by their increased power in facial GWAS and RVAS.

Humans↗

PubMed2006

Minor physical anomalies in schizophrenia: a meta-analysis.

Numerous studies report an increased frequency of minor physical anomalies (MPAs) in schizophrenic individuals compared with controls. However, these studies vary considerably regarding the magnitude of the case-control disparity and the topographical distribution of the anomalies. A meta-analysis was carried out on the existing MPA literature in an effort to better understand the relationship between MPAs and schizophrenia. Following a literature search, 13 studies were identified that met our inclusion criteria. Mean total MPA scores were available for 11 of these studies, whereas only seven studies provided regional MPA scores. For both the total MPA and regional MPA analyses, pooled effect sizes (Hedges' g and pooled odds ratios, respectively) were calculated along with tests of heterogeneity. For the total MPA analyses, a meta-regression approach was used to explore the relationship between possible moderator variables (e.g., number of MPA scale items) and effect size heterogeneity. The magnitude of the pooled effect size for the total MPA scores was high (1.131; p<0.001), indicating significantly more overall MPAs in schizophrenic individuals. Significant effect size heterogeneity was present (p<0.001); however, this heterogeneity could not be explained by any of the included moderator variables. The regional MPA analysis revealed significantly increased MPAs in all six anatomical regions (p<0.05), although the pooled odds ratios for these regions did not differ significantly from one another. These results suggest a lack of regional specificity for MPAs in schizophrenia.

Adult↗

PubMed2006

Anthropometric precision and accuracy of digital three-dimensional photogrammetry: comparing the Genex and 3dMD imaging systems with one another and with direct anthropometry.

A variety of commercially available three-dimensional (3D) surface imaging systems are currently in use by craniofacial specialists. Little is known, however, about how measurement data generated from alternative 3D systems compare, specifically in terms of accuracy and precision. The purpose of this study was to compare anthropometric measurements obtained by way of two different digital 3D photogrammetry systems (Genex and 3dMD) as well as direct anthropometry and to evaluate intraobserver precision across these three methods. On a sample of 18 mannequin heads, 12 linear distances were measured twice by each method. A two-factor repeated measures analysis of variance was used to test simultaneously for mean differences in precision across methods. Additional descriptive statistics (e.g., technical error of measurement [TEM]) were used to quantify measurement error magnitude. Statistically significant (P < 0.05) mean differences were observed across methods for nine anthropometric variables; however, the magnitude of these differences was consistently at the submillimeter level. No significant differences were noted for precision. Moreover, the magnitude of imprecision was determined to be very small, with TEM scores well under 1 mm, and intraclass correlation coefficients ranging from 0.98 to 1. Results indicate that overall mean differences across these three methods were small enough to be of little practical importance. In terms of intraobserver precision, all methods fared equally well. This study is the first attempt to simultaneously compare 3D surface imaging systems directly with one another and with traditional anthropometry. Results suggest that craniofacial surface data obtained by way of alternative 3D photogrammetric systems can be combined or compared statistically.

Anthropometry↗

PubMed2006

Candidate genes for oral-facial clefts in Guatemalan families.

Nonsyndromic cleft lip +/- cleft palate (CL/P) is a complex trait of unknown etiology. Most genetic studies of CL/P define affection status in a way that ignores subtle subclinical manifestations, resulting in a potential loss of statistical power. This study investigated 10 candidate genes in 155 individuals from 25 Guatemalan CL/P families. High-resolution ultrasound images of the orbicularis oris (OO) muscle were obtained. CL/P was present in 28 family members; an additional 10 had subcutaneous OO muscle defects. Family-based association studies were performed for both narrow (CL/P only) and broad (CL/P plus OO muscle defects) definitions of affection status. PVRL1 was significantly associated under both definitions (P = 0.04, narrow; P = 0.02, broad). Association with JAG2 improved from P = 0.09 under the narrow definition to P = 0.04 under the broad definition. Broadening the oral-facial cleft phenotype to include subclinical variants may improve power in genetic studies.

Chromosome Aberrations↗

PubMed2006

Characterization of dermatoglyphics in PHOX2B-confirmed congenital central hypoventilation syndrome.

OBJECTIVE: Individuals with congenital central hypoventilation syndrome have characteristic variants in the PHOX2B gene (primarily polyalanine expansion mutations). The PHOX2B gene acts as a transcriptional activator in the promotion of pan-neuronal differentiation in the autonomic nervous system during early embryologic development, with a primary role in the sympathetic noradrenergic phenotype in vertebrates. Because sympathetic innervation has been hypothesized to affect the development of dermatoglyphic pattern types, we hypothesized that individuals with PHOX2B-confirmed congenital central hypoventilation syndrome would have characteristic dermatoglyphic patterning and that the dermatoglyphic phenotype would be related to the disease-defining PHOX2B genotype. METHODS: Dermatoglyphic pattern type frequency, left/right symmetry, and genotype/phenotype correlation were assessed for 33 individuals with PHOX2B-confirmed congenital central hypoventilation syndrome and compared with published control data. RESULTS: Dermatoglyphic pattern type frequencies were altered in congenital central hypoventilation syndrome cases versus controls. In particular, there was an increase of arches in females and ulnar loops in males, with the largest differences for the left hand and for individuals with both congenital central hypoventilation syndrome and Hirschsprung disease. Dissimilarity scores between the congenital central hypoventilation syndrome and congenital central hypoventilation syndrome + Hirschsprung disease cases were not significantly different, nor were dissimilarity scores between all of the female and all of the male cases. No significant association was found between the number of polyalanine repeats in the PHOX2B genotypic category and dermatoglyphic pattern frequencies in the congenital central hypoventilation syndrome study groups. CONCLUSIONS: These results represent the first report describing specific dermatoglyphic patterning in congenital central hypoventilation syndrome and suggest a relationship between PHOX2B and the expression of dermatoglyphic pattern types. An expanded congenital central hypoventilation syndrome data set to include the full spectrum of PHOX2B mutations is necessary to further delineate the role of PHOX2B in dermatoglyphic patterning.

Adolescent↗

PubMed2006

The Pittsburgh Oral-Facial Cleft study: expanding the cleft phenotype. Background and justification.

The Pittsburgh Oral-Facial Cleft study was begun in 1993 with the primary goal of identifying genes involved in nonsyndromic orofacial clefts in a variety of populations worldwide. Based on the results from a number of pilot studies and preliminary genetic analyses, a new research focus was added to the Pittsburgh Oral-Facial Cleft study in 1999: to elucidate the role that associated phenotypic features play in the familial transmission patterns of orofacial clefts in order to expand the definition of the nonsyndromic cleft phenotype. The purpose of this paper is to provide a comprehensive review of phenotypic features associated with nonsyndromic orofacial clefts. These features include fluctuating and directional asymmetry, non-right-handedness, dermatoglyphic patterns, craniofacial morphology, orbicularis oris muscle defects, dental anomalies, structural brain and vertebral anomalies, minor physical anomalies, and velopharyngeal incompetence.

Brain↗

PubMed2005

Facial phenotype in children and young adults with PHOX2B-determined congenital central hypoventilation syndrome: quantitative pattern of dysmorphology.

Congenital central hypoventilation syndrome (CCHS) is caused by mutations in PHOX2B, which is essential for maturation of the neural crest into the autonomic nervous system and is expressed in the dorsal rhombencephalon, a region that gives rise to facial structures. Digital photographs of 45 individuals with PHOX2B-confirmed CCHS, and 45 matched controls were analyzed for 17 linear and 6 angular measurements, and 9 derived indices. Paired t tests were used to compare group means, correlation was calculated between PHOX2B polyalanine expansion number and facial measures, and stepwise logistic regression was used to predict case-control and genotype status. CCHS cases differed significantly from controls on 13 variables (6 after p value correction: nasolabial angle, upper lip height, lateral lip height, facial index, upper facial index, and presence of inferior inflection of the lateral segment of the upper lip vermillion border). Five variables were able to predict correctly 85.7% of CCHS cases and 82.2% of controls: upper lip height, biocular width, upper facial height, nasal tip protrusion, and inferior inflection of the upper lip vermillion border. A negative relationship between number of repeats and four anthropometric measures was observed: mandible breadth, nasolabial angle, lateral lip height, and mandible-face width index. These results suggest a characteristic facial phenotype in children and young adults with CCHS, due to an expansion mutation in PHOX2B.

Adolescent↗

PubMed2005

Evaluation of non-metric variation in the crania of black and white perinates.

Reports in the literature suggest that diagnostic differences in craniofacial morphology between blacks and whites arise very early in development. These reports, however, have not been consistent regarding which traits are diagnostic and have failed to provide forensic anthropologists with a reliable method of assessment. In an effort to clarify the situation, 13 non-metric craniofacial traits were scored and analyzed statistically in a sample of 70 black and white perinatal specimens obtained from the Smithsonian's fetal osteology collection. Chi-square analysis revealed significant (p<0.05) differences in the distribution of five of the 13 non-metric traits examined. Compared with black perinates, white perinates more frequently possessed a relatively narrow supraoccipital portion of the occipital bone, a prominent anterior nasal spine, "deep" subnasal margins, an elongated vomer, and semi-circular temporal squamae. When these five traits were entered into a stepwise logistic regression, temporal squamous shape, vomer shape and subnasal margin definition were found to be predictive of race (79.1% overall correct classification). An independent sample of 39 black and white perinates was then used to validate the results; overall, 67.5% of the validation sample could be classified correctly. Reasons for the disparity in correct classification rates between the initial and follow-up sample are provided. Results of the present study may be useful for anthropologists who encounter unidentified cranial material from this age range.

Black People↗

PubMed2005

Hair whorls and handedness: informative phenotypic markers in nonsyndromic cleft lip with or without cleft palate (NS CL/P) cases and their unaffected relatives.

Cleft lip with or without cleft palate (CL/P) is a complex disorder with a range of phenotypic manifestations and a birth prevalence that varies by population (1/500-1/2,000). Investigators have postulated that CL/P cases may have abnormal brain development, citing structural brain differences, and cognitive impairments in affected individuals. Previously, increased levels of non-right handedness (NRH), a marker for abnormal brain lateralization, have also been demonstrated in CL/P cases. Atypical hair whorls, more direct markers of altered brain development, may be related to NRH. To date, neither hair whorl patterns nor their relationship to NRH have been studied in a CL/P population. In the current study, we investigate the hypothesis that altered brain development is part of the phenotypic spectrum of NS CL/P by assessing NRH and atypical hair whorls in CL/P families. The study population included 49 nonsyndromic CL/P cases and 116 of their unaffected relatives; 21.8% of the study population was NRH compared to the 10% population estimate (P < 0.0001). Counter-clockwise hair whorls (CCW) were found in 12.7% of all subjects compared to a population rate of 9.9 %. Of all subjects, 11% of the NRH individuals had CCW, which was similar to the frequency of CCW in right-handed individuals. Approximately 80% of the whorls were placed on either the right or center of the scalp. No significant associations were found between the type of cleft and handedness, hair whorl rotation, or placement. These results suggest that certain phenotypic markers of abnormal brain development may comprise part of the extended phenotype of orofacial clefting.

Abnormalities, Multiple↗

PubMed2005

Three-dimensional surface imaging: limitations and considerations from the anthropometric perspective.

The use of three-dimensional (3D) surface imaging for clinical measurement purposes has increased considerably as the technology has become more affordable. Like any measurement technique, 3D surface-based anthropometry is subject to a number of limitations and methodological caveats and thus should not be applied without sufficient consideration of its potential strengths and weaknesses. In this brief report, the authors consider 3D surface imaging from the anthropometric perspective, specifically focusing on issues related to the capture of reliable quantitative information from the head and face.

Anthropometry↗

PubMed2005

Dermatoglyphic fingerprint heterogeneity among individuals with nonsyndromic cleft lip with or without cleft palate and their unaffected relatives in China and the Philippines.

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.

Analysis of Variance↗

PubMed2005

Bilateral asymmetry in Chinese families with cleft lip with or without cleft palate.

OBJECTIVE: To determine if Chinese individuals with nonsyndromic cleft lip with or without cleft palate (CL/P) display more bilateral asymmetry than do their unaffected relatives. DESIGN/SUBJECTS: A case-control study of 313 individuals with CL/P from Shanghai, China, with 201 unaffected relatives as controls. METHODS: Size-adjusted asymmetry scores were defined by data on middle-finger length, palm length, palpebral fissure width, and ear length. Case-control comparisons used a multivariate repeated measures analysis of variance, paired t tests, and the Wilcoxon signed rank test. RESULTS: The ear-length measure showed a significant increase in fluctuating asymmetry (FA) in individuals with CL/P compared with their unaffected relatives, which was most pronounced in the female cleft lip and palate subgroup (p = .04). No other measures showed any increase in FA. CONCLUSION: Evidence was found for increased FA, as measured by overall ear length, in Chinese individuals with nonsyndromic CL/P, compared with their unaffected family members. The use of bilateral measurements other than dermatoglyphics may prove to be a valuable means of assessing overall developmental stability in individuals with developmental malformations and in their families.

Analysis of Variance↗

PubMed2005

Dermatoglyphic pattern types in subjects with nonsyndromic cleft lip with or without cleft palate (CL/P) and their unaffected relatives in the Philippines.

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.

Case-Control Studies↗

PubMed2004

Digital three-dimensional photogrammetry: evaluation of anthropometric precision and accuracy using a Genex 3D camera system.

OBJECTIVE: To determine the precision and accuracy of facial anthropometric measurements obtained through digital three-dimensional (3D) photogrammetry. DESIGN: Nineteen standard craniofacial measurements were repeatedly obtained on 20 subjects by two independent observers, using calipers and 3D photos (obtained with a Genex 3D camera system), both with and without facial landmarks labeled. Four different precision estimates were then calculated and compared statistically across techniques. In addition, mean measurements from 3D photos were compared statistically with those from direct anthropometry. RESULTS: In terms of measurement precision, the 3D photos were clearly better than direct anthropometry. In almost all cases, the 3D photo with landmarks labeled had the highest overall precision. In addition, labeling landmarks prior to taking measurements improved precision, regardless of method. Good congruence was observed between means derived from the 3D photos and direct anthropometry. Statistically significant differences were noted for seven measurements; however, the magnitude of these differences was often clinically insignificant (< 2 mm). CONCLUSIONS: Digital 3D photogrammetry with the Genex camera system is sufficiently precise and accurate for the anthropometric needs of most medical and craniofacial research designs.

Adolescent↗