Mary L Marazita

• B.S., Ph.D., FACMG
• Managing Director at University of Pittsburgh

Purpose Facial dysmorphism is a feature of many monogenic disorders, and is important in diagnostics, variant interpretation and nosology. Nevertheless, comprehensively assessing the complex facial shape changes associated with specific syndromes remains challenging. Here, we present 3D morphometric approaches to overcome these limitations, utilizi...

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 interpret...

Background Fifth finger clinodactyly describes the conspicuous curvature of the fifth digit toward the other digits of the hand. Phenotypic expression can range from mild and almost imperceptible to severe, where function is impacted, and clinical intervention may be required. Although classically considered an autosomal dominant trait based on ear...

De novo variants (DNs) are sporadically occurring variants that most commonly arise in the germline and are present in offspring but absent in both parents. As they are not under selective pressure, they may be enriched for disease-causing alleles and have been implicated in multiple rare genetic disorders. Cleft palate (CP) is a common craniofacia...

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 va...

Orofacial clefts (OFCs) are the most common craniofacial birth defects, affecting 1 in 700 births, and have a strong genetic basis with a high recurrence risk within families. While many of the previous studies have associated common, noncoding genetic loci with OFCs, previous studies on de novo variants (DNVs) in OFC cases have focused on coding v...

Objectives Nonsyndromic orofacial clefts (OFCs) etiology involves multiple genetic and environmental factors with over 60 identified risk loci; however, they account for only a minority of the estimated risk. Epigenetic factors such as differential DNA methylation (DNAm) are also associated with OFCs risk and can alter risk for different cleft type...

Nonsyndromic orofacial clefts (OFCs) are common, heritable birth defects caused by both genetic and environmental risk factors. Despite the identification of many genetic loci harboring OFC-risk variants, there are many unknown genetic determinants of OFC. Furthermore, while the process of embryonic facial development is well characterized, the mol...

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of approximately 1 in 35,000 live births, it is the most common form of syndromic clefting and may account for ∼2% of all OFCs. The majority of VWS is attributed to genetic variants in IRF6 (∼70%) or GRHL3 (∼...

Non-syndromic orofacial clefts (NSOC) are common craniofacial birth defects, and result from both genetic and environmental factors. NSOC include three major sub-phenotypes: non-syndromic cleft lip with palate (NSCLP), non-syndromic cleft lip only (NSCLO) and non-syndromic cleft palate only (NSCPO), NSCLP and NSCLO are also sometimes grouped as non...

Human craniofacial shape is highly variable yet highly heritable with numerous genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify...

Objectives Dental caries and periodontitis are among the most prevalent chronic diseases worldwide and have been associated with atherosclerotic cardiovascular diseases (ASCVD). This study aimed to determine (1) the independent associations between subclinical ASCVD markers (carotid intima media thickness [CIMT] and coronary artery calcification [C...

Structural birth defects affect 3–4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific r...

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 interpre...

Objective Torus Palatinus (TP) is a common trait with an unclear aetiology. Although prior studies suggest a hereditary component, the genetic factors that influence TP risk remain unknown. The purpose of this study is to identify genetic variants associated with TP. Materials and Methods We assessed the TP status of 829 individuals from various a...

Objectives Oral health during the perinatal period and beyond affects the health and well‐being of women and their offspring. Oral self‐care behaviours can maintain or improve oral health; depression or stress during the perinatal period may compromise these behaviours. The aim of the study was to investigate the independent and combined effects of...

Structural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific r...

Orofacial clefts (OFCs) are among the most common human congenital birth defects. Previous multiethnic studies have identified dozens of associated loci for both cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP). Although several nearby genes have been highlighted, the “casual” variants are largely unknown. Here, we develope...

Craniosynostosis (CS) is a major birth defect resulting from premature fusion of cranial sutures. Nonsyndromic CS occurs more frequently than syndromic CS, with sagittal nonsyndromic craniosynostosis (sNCS) presenting as the most common CS phenotype. Previous genome-wide association and targeted sequencing analyses of sNCS have identified multiple...

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual’s genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether...

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry populati...

Background: Pregnancy is associated with increased risk of caries, but the extent this increase extends into the postpartum period is poorly understood. Study Objective: Describe the epidemiology of dental decay in the postpartum period among Black/African American and White American women and explore associations with potentially modifiable risk f...

Human craniofacial shape is highly variable yet highly heritable with genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify genomic l...

Introduction: Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. Methods: Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This p...

The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yiel...

As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies have demonstrated that there are genetic differences between the different phenotypic presentations of OFCs. However, the contribution of rare genetic variation genome-wide to different subtypes of OFCs has been understudied...

A genome-wide association study (GWAS) of a complex, multi-dimensional morphological trait, such as the human face, typically relies on predefined and simplified phenotypic measurements, such as inter-landmark distances and angles. These measures are predominantly designed by human experts based on perceived biological or clinical knowledge. To avo...

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We per...

Abstract Introduction: The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large-scale population genomic studies. The availability of data from the first whole-genome sequencin...

Orofacial clefts (OFC) remain among the most prevalent congenital abnormalities worldwide. In the United States in 2010 to 2014, 16.2 of 10,000 live births are born with OFC compared with 23.6 of 10,000 in Alta Verapaz, Guatemala in 2012. Demographics and cleft severity scores were retrospectively gathered from 514 patients with isolated OFC at the...

By age 5, approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a sco...

Exome sequencing (ES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for ES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex etiologi...

Purpose: Orofacial clefts (OFCs) are common birth defects including cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP). OFCs have heterogeneous etiologies, complicating clinical diagnostics as it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or...

The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequenc...

Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This pipeline first adopts sp...

As one of the most common structural birth defects, orofacial clefts (OFCs) have been studied for decades, and recent studies have demonstrated that there are genetic differences between the different phenotypic presentations of OFCs. However, the contribution of rare genetic variation genome-wide to different subtypes of OFCs has been understudied...

Genotype-by-environment interactions (GEI) may influence dental caries, although their effects are difficult to detect. Variance quantitative trait loci (vQTL) may serve as an indicator of underlying GEI effects. The aim of this study was to investigate GEI effects on dental caries by prioritizing variants from genome-wide vQTL analysis. First, we...

Orofacial clefts (OFCs) are the most common craniofacial birth defects, and are often categorized into two etiologically distinct groups: cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP). CP is highly heritable, but there are still relatively few established genetic risk factors associated with its occurrence compared to...

Muscle spindles are sensory receptors in skeletal muscle that provide information on muscle length and velocity of contraction. Previous studies noted that facial muscles lack muscle spindles, but recent reports indicate that the human platysma muscle and "buccal" muscles contain spindles. Mammalian facial muscles are active in social communication...

Whole-exome sequencing (WES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for WES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex...

AMOTL1 encodes angiomotin‐like protein 1, an actin‐binding protein that regulates cell polarity, adhesion, and migration. The role of AMOTL1 in human disease is equivocal. We report a large cohort of individuals harboring heterozygous AMOTL1 variants and define a core phenotype of orofacial clefting, congenital heart disease, tall stature, auricula...

Introduction Van der Woude Syndrome (VWS) is an autosomal dominant disorder responsible for 2% of all syndromic orofacial clefts (OFCs) with IRF6 being the primary causal gene (70%). Cases may present with lip pits and either cleft lip, cleft lip with cleft palate, or cleft palate, with marked phenotypic discordance even among individuals carrying...

Objectives: To describe the association between household food insecurity and intake of cariogenic foods that increase risk of dental caries. Methods: Cross-sectional analysis of 842 mothers in Appalachia and their children participating in the Center for Oral Health Research Cohort 2 between 2011 and 2017 when their children were ~ 24 months of a...

Background: By age five approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic sco...

Background Early childhood caries (ECC)—dental caries (cavities) occurring in primary teeth up to age 6 years—is a prevalent childhood oral disease with a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial community lead...

Although genetics affects early childhood caries (ECC) risk, few studies have focused on finding its specific genetic determinants. Here, we performed genome-wide association studies (GWAS) in five cohorts of children (aged up to 5 years, total N = 2974, cohorts: Center for Oral Health Research in Appalachia cohorts one and two [COHRA1, COHRA2], Io...

This chapter reviews the epidemiology, etiology, and genetic risk factors for syndromic and non‐syndromic orofacial clefting (OFC), as well as genetic counseling for affected families. Maternal smoking during pregnancy is the most replicated risk factor for OFC. OFCs show strong familial aggregation, which suggests a strong genetic component to the...

The cranial vault - the portion of the skull surrounding the brain and cerebellum - is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conducted a joint multi-ancestry and admixed multivariate GWAS on 3D cranial vault shape extracted from magnetic resonance images of 6,772 childr...

Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts. We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P ca...

This chapter reviews the evidence of gene × environment interactions (G × E) in the etiology of orofacial cleft birth defects (OFCs), specifically cleft lip (CL), cleft palate (CP), and cleft lip with or without cleft palate (CL/P). We summarize the current state of our understanding of the genetic architecture of nonsyndromic OFCs and the evidence...

Objectives Examine whether mothers perceived that child oral health was a source of conflict in family relationships. Methods This cross-sectional qualitative study consisted of 126 semi-structured interviews with mothers of 3–5 year-old children from West Virginia and Pittsburgh, Pennsylvania. Interviews consisted of open-ended questions on the m...

Background Added sugar in children’s diets puts them at higher risk of developing caries. Researchers have reported that grandparents frequently give their grandchildren cariogenic foods and beverages (for example, those with added sugars) and disagreements between grandparents and parents can ensue over this issue. This study's objective was to ex...

Objective: To evaluate the associations between time-varying factors (mother's oral health, oral hygiene, smoking habits, diet, food insecurity and stress) socioeconomic factors (mother's employment, marital status, household income, insurance status, household size) and medical history on children's risk of developing a carious lesion in the firs...

Objective Describe associations between dental caries and dental plaque microbiome, by dentition and family membership. Methods This cross-sectional analysis included 584 participants in the Center for Oral Health Research in Appalachia Cohort 1 (COHRA1). We sequenced the 16S ribosomal RNA gene (V4 region) of frozen supragingival plaque, collected...

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseas...

Purpose Orofacial clefts (OFCs) are common birth defects including cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP). OFCs have heterogeneous etiologies, complicating clinical diagnostics as it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sp...

The objective of this study was to evaluate whether dietary habits at age 2 associate with sleep duration trajectories through age 5 in children from north and central Appalachia. A total of 559 children from the Center for Oral Health Research in Appalachia (COHRA) cohort 2 were followed via caregiver phone interviews up to six times between ages...

Mild curvature of the fifth finger (or clinodactyly) is a relatively common trait. While severe forms can cause functional impairment and are a feature of certain congenital syndromes, mild clinodactyly is considered a minor morphological variant. Despite exhibiting continuous variation, clinodactyly is rarely treated as a quantitative trait. Conse...

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent tri...

Children with orofacial clefting (OFC) present with a wide range of dental anomalies. Identifying these anomalies is vital to understand their etiology and to discern the complex phenotypic spectrum of OFC. Such anomalies are currently identified using intra-oral exams by dentists, a costly and time-consuming process. We claim that automating the p...

Individuals with orofacial clefting (OFC) have a higher prevalence of tooth agenesis (TA) overall. Neither the precise etiology of TA, nor whether TA occurs in patterns that differ by gender or cleft type is yet known. This meta-analysis aims to identify the spectrum of tooth agenesis patterns in subjects with non-syndromic OFC and controls using t...

Importance: Fluoride delivered either topically (eg, fluoride varnish) or systemically (eg, water fluoridation, prescription fluoride supplements) is widely used as a caries preventive agent in children. The widespread existence of misinformation, including inaccurate information that attaches negative values or suspicion to fluoride treatments, r...

Background Dental caries is the most common chronic childhood disease. Past studies reveal that grandparents provide their grandchildren with cariogenic foods and beverages (e.g., those with free sugars and/or modified starches). Qualitative research can help identify what drives this phenomenon. Objectives To examine mothers’ explanations for why...

Objective: To explore the association of racism in oral healthcare settings and dental care-related fear/anxiety with dental utilization among Black/African American women in Appalachia. Methods: We analyzed self-report measures of racism in oral healthcare settings, dental care-related anxiety and fear, recency of a dental visit, and demographi...

Introduction Enamel hypoplasia causes a reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. Methods A gen...

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect, affecting approximately 1 in 700 births. NSCL/P has complex etiology including several known genes and environmental factors; however, known genetic risk variants only account for a small fraction of the heritability of NSCL/P. It is commonly suggested that gene...

Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and...

Objectives To examine whether information that mothers received from dentists in their social network was consistent with professional recommendations for the first dental visit at age 1 y. Methods We performed a cross-sectional qualitative study on mothers in Pennsylvania and West Virginia from 2018 to 2020 to explore how their social networks in...

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact DNMs that contribute to the risk of nsCL/P, we conducted whole genome sequencing (WGS) analyses in 130 African case-parent trios (affected prob...

Children with orofacial clefting (OFC) present with a wide range of dental anomalies. Identifying these anomalies is vital to understand their etiology and to discern the complex phenotypic spectrum of OFC. Such anomalies are currently identified using intra-oral exams by dentists, a costly and time-consuming process. We claim that automating the p...

Risk loci identified through genome-wide association studies have explained about 25% of the phenotypic variations in nonsyndromic orofacial clefts (nsOFCs) on the liability scale. Despite the notable sex differences in the incidences of the different cleft types, investigation of loci for sex-specific effects has been understudied. To explore the...

Dental caries (cavities), one of the most common infectious diseases, is caused by a number of factors. Oral microbes, dietary practices, sociodemographic factors, and dental hygiene all inform caries risk. Assessing the impact of diet is complicated as individuals eat foods in combinations, and the interactions among the foods may alter caries ris...

Orofacial clefts (OFCs) are among the most common craniofacial birth defects and constitute a high public health burden around the world. OFCs are phenotypically heterogeneous, affecting only the lip, only the palate, or involving both the lip and palate. Cleft palate alone is demonstrably a genetically distinct abnormality from OFCs that involve t...

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross‐study analyses for biomedical research. An expert review panel (ERP) reviewed and updated the PhenX Toolkit Speech and Hearing domain to improve the precision and consistency of speech, language, and hearing disorder pheno...

Background Early childhood caries (ECC) – dental caries (cavities) occurring in primary teeth up to age 6-years - is a prevalent childhood oral disease that includes a microbial etiology. Streptococcus mutans was previously considered a primary cause, but recent research promotes the ecologic hypothesis, in which a dysbiosis in the oral microbial c...

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies fo...

Objective: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring....

The human face is a highly complex and variable structure resulting from the intricate coordination of numerous genetic and non-genetic factors. Hundreds of genomic loci impacting quantitative facial features have been identified. While these associations have been shown to influence morphology by altering the mean size and shape of facial measures...

Abstract Background Dental caries is one of the most common chronic diseases and is influenced by a complex interplay of genetic and environmental factors. Most previous genetic studies of caries have focused on identifying genes that contribute to dental caries in specific ethnic groups, usually of European descent. Methods The aim of this study i...

Objectives: Palatal shape contains a lot of information that is of clinical interest. Moreover, palatal shape analysis can be used to guide or evaluate orthodontic treatments. A statistical shape model (SSM) is a tool that, by means of dimensionality reduction, aims at compactly modeling the variance of complex shapes for efficient analysis. In th...

This study aimed to determine the normative facial anthropometry measurement among Nigerians using three-dimensional stereophotogrammetry analysis. This study was carried out in Lagos, Nigeria over a period of 3 years. The sample population was Nigerians of diverse ethnic groups, age 16 and above with no history of congenital or acquired craniofac...

Use of dental services in childhood, especially preventive care, is associated with many important oral health outcomes throughout life. The Andersen behavioral model of healthcare utilization posits that predisposing characteristics, enabling resources, and need factors predict utilization in oral and other healthcare domains. Inequities that prod...

Based on epidemiologic and embryologic patterns, nonsyndromic orofacial clefts– the most common craniofacial birth defects in humans– are commonly categorized into cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which are traditionally considered to be etiologically distinct. However, some evidence of shared genetic risk...

Modern human palate shape has been reported to vary by sex and ancestry, but limitations in the methods used to quantify shape and in population coverage have led to inconsistent findings. In the present study, the authors aim to characterize the effects of sex and ancestry on normal-range three-dimensional palate shape through landmark-based morph...

Objectives: The aim of the study is to highlight variations in facial anthropometric measurements among the major ethnic groups in Nigeria using 3D photogrammetry. Materials and Methods: This study was conducted in Lagos, Nigeria. Acquisition of 3D facial photographs was done using a Vectra H1 portable 3D photogrammetry imaging system. Descriptive...

Background The bacteriome is associated with susceptibility to some eukaryotic viruses, but no study has examined associations between the salivary bacteriome and human herpesviruses (HHVs). We provide new prevalence and incidence estimates for salivary herpesviruses detection and estimate associations with bacteriome diversity in young children....

Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include a cleft lip (CL) and cleft lip and palate (CLP). These OFC subtypes are also heterogeneous themselves, with the CL occurring on the left, right, or both sides of the upper lip. Unilateral CL and CLP have a 2:1 bias towards left-sided clefts, suggesting a nonr...