Demographics of consanguinity in Palestinians with orofacial clefts: a non-randomised longitudinal study

Abstract

Background Orofacial clefts (OFCs) are the most common craniofacial malformation at birth worldwide, with an incidence of 1•05 out of 1000 live births in the occupied Palestinian territory. The majority of OFCs present as singletons (without a family history of clefts), and a minority present as multiplex cases (greater than one OFC in the family). Consanguineous marriages (marriage between blood relatives) among Palestinians is approximately 40%. This study aims to define the incidence and impact of multiplicity in Palestinians with OFC, and to determine how his may be related to rates of consanguinity. Methods We conducted a non-randomised longitudinal study using a 700-question survey administered in colloquial Arabic to mothers of patients with congenital anomalies (including patients with any craniofacial anomaly). Volunteer researchers fluent in English and Arabic were trained to recruit participants and administer surveys during craniofacial surgery screening events in Palestinian Government Hospitals. Selection criteria were a child in the family with an orofacial cleft, and family consent for participation in the survey. In a non-probability sampling method, the frequency of OFC in immediate and distant family members, and the extent of consanguineous marriages, were documented. Comparisons were made using chi squared tests; p<0•05 was considered statistically significant. The study methods and questionnaire were approved by the Institutional Review Board of Cincinnati Children's Hospital Medical Complex (IRB 2015-0607). Informed written consent was obtained from participants and legal guardians. Findings Of 613 completed surveys, 536 reported OFC, among whom 265 families (46%) reported another family member with a cleft, and 271 did not. Among multiplex families, 26% of OFCs (69 of 265) were in first-degree relatives (parents or siblings), 74% (196) in distant relatives, and 15% (39) in both. Nearly half of the patients from multiplex families (118) represented 42 families with multiple clefts. Compared with families in which only one member had a cleft, patients from multiplex families were more likely to be diagnosed with a cleft lip (29% vs 18%; p<0•01), less likely to be diagnosed with a cleft lip and palate (37% vs 48%; p=0•02), and had a similar likelihood of being diagnosed with a cleft palate alone. Patients from multiplex families were more likely to come from Hebron (52%) than from any other city in the West Bank (39%; p<0•01), and were more likely to have family members with non-cleft birth anomalies (61% vs 13%; p<0•001). Parents of children with clefts in a multiplex family were more likely to be consanguineous (related to each other) than parents of singletons (60% vs 40%; p<0•01). Interpretation The percentage of multiplex families (46%) in this study appears to be higher than reported previously from the Middle East (including Iran and Saudi Arabia). There also appears to be a higher rate of consanguinity among multiplex families than reported previously, especially among those families ...