The International Family Study of Nonsyndromic Orofacial Clefts: Design and Methods

Abstract

Background: The majority of research to understand the risk factors of nonsyndromic orofacial clefts (NSOFCs) has been conducted in high-income populations. Although patients with NSOFCs in low- and middle-income countries (LMICs) are at the highest risk of not receiving care, global health infrastructure allows innovative partnerships to explore the etiologic mechanisms of cleft and targets for prevention unique to these populations. Methods: The International Family Study (IFS) is an ongoing case–control study with supplemental parental trio data designed to examine genetic, environmental, lifestyle, and sociodemographic risk factors for NSOFCs in 8 LMICs (through August 2020). Interview and biological samples are collected for each family. The interview includes demographics, family history of cleft, diet and water sources, maternal pregnancy history, and other lifestyle and environmental factors. Results: Seven of 8 countries are currently summarized (2012-2017) for a total of 2955 case and 2774 control families with 11 946 unique biological samples from Vietnam, Philippines, Honduras, Madagascar, Morocco, Democratic Republic of the Congo, and Nicaragua. The phenotype distribution was 1641 (55.5%) cases with cleft lip and palate, 782 (26.5%) with cleft lip (CL), and 432 (14.6%) with cleft palate (CP). Discussion: The International Family Study is the largest case set of NSOFCs with an associated biobank in LMICs currently assembled. The biobank, family, and case–control study now include samples from 8 LMICs where local health care infrastructure cannot address the surgical burden of cleft or investigate causal mechanisms. The International Family Study can be a source of information and may collaborate with local public health institutions regarding education and interventions to potentially prevent NSOFCs.

Co‐occurring anomalies in congenital oral clefts

“…OCs, the most frequent craniofacial congenital anomalies, are often associated with other congenital anomalies (Gil-da-Silva-Lopes et al, 2020). These associated anomalies are responsible of the morbidity and the mortality associated with OCs (Auslander et al, 2021;Williams et al, 2007). However, the reported prevalence as well and the type and the percentage of anomalies associated with OCs varied considerably among the various reported studies (Tables 4 and 5).…”

Perfil epidemiológico y presencia de polimorfismos IFR6 (rs2235371), TGFA (rs3771494) en individuos con labio y paladar hendido no sindrómico

“…En México, la incidencia se presenta en 1 por cada 2000 nacimientos por año 1 . Por otra parte, la prevalencia muestra una distribución heterogénea pues, del total de los casos de LPH, esta se ha reportado desde un 50% 6 , mostrando un 70% 7 , hasta alcanzar un 93-95% en su entidad no sindrómica 8 , Adicional a lo anterior, es importante mencionar que el LPH además de afectar la estética, tiene un impacto negativo y severo en la nutrición, la calidad de vida, la salud bucal, el desarrollo de habilidades y de lenguaje de quienes la padecen, situación que se agrava en la edad pediátrica por la implicación del desarrollo y crecimiento que, de no corregirse, se continúa en la etapa adulta [9][10][11][12] .…”