A Preliminary Investigation into Orofacial Clefts in the Central and Western Regions of Saudi Arabia

  • Heba J. Sabbagh

    Student thesis: Doctoral ThesisDoctor of Dental Science


    Background and aims: Clefts of the lip and palate are the most common types of craniofacial birth defects found worldwide. This study is the first multicentre case-control triad (of children and their parents) in Saudi Arabia that aims to: (I) measure the prevalence of non-syndromic orofacial cleft (NSOFC) at birth and (II) investigate the genetic and environmental risk factors associated with NSOFC in infants attending government hospitals in the Western and Central Regions of Saudi Arabia.
    Material and methods: Two hundred and seventeen non-syndromic orofacial cleft (NSOFC) triads comprising probands aged 18 months or less were selected from eleven hospitals in three main cities of Saudi Arabia (Jeddah, Maddina, and Riyadh). Patients were examined to identify cleft phenotype according to the LASHAL classification. Cases born in the designated hospitals from January 2010 to January 2012 were compared with the total number of births, in the same period of time to measure the prevalence of CL/P and CP in Saudi Arabia. Cases were compared with 244 control triads matched for proband age, gender and location to assess the environmental and genetic (IRF6 and VAX1 genes) aetiology of NSOFC through a questionnaire and infant-parental triad saliva sample. Gene-environmental interaction (GEI) was assessed through measuring the distribution of maternal genotypes and alleles according to exposure/no-exposure environmental factors.
    Results: The prevalence of NSOFC in government hospitals in the Western and Central regions of Saudi Arabia was 1.17/1000 births.
    Environmental risk factors (ERFs) significantly related to NSOFC after the odds ratios were adjusted through logistic regression included; family history for NSOFC, folic acid, antibiotic use, common cold/flu, maternal stress, paternal waterpipe smoking, incense exposure, maternal exposure to chemicals and maternal main water source.
    Genetic analysis revealed significant over-transmission of the common IRF6 allele rs2013162 in CL/P families using Family based association test (FBAT) analysis and paternal transmission using PLINK testing. Two haplotypes containing the rare alleles of VAX1 rs4752028 and IRF6 rs2013162 were significantly associated with NSOFC. VAX1 showed significant difference between cases and controls infant parental triad.
    Gene-environment interaction (GEI) found a significant relationship between maternal SNP (IRF6 rs2013162 and/or VAX1 rs7078160) and maternal folic acid pre-gestation ingestion, antipyretic medication ingestion, fever, abdominal pain, high blood pressure, passive smoking, maternal stress and paternal waterpipe smoking, and /or maternal passive smoking
    • The prevalence of NSOFC in Saudi Arabia (1.17/1000 births) is marginally lower than global average figures (1.25/1000births)
    • Maternal exposure to common cold/flu, folic acid supplementation, stress, antibiotic use, incense, source of drinking water, paternal waterpipe smoking and intense paternal tobacco smoking are associated with increased risk of CL/P and/or CP in Saudi Arabia.
    • IRF6 rs2013162 showed significant over transmission of the common allele (C) with CL/P cases. Also, VAX1 rs4752028 and rs7078160 rare allele are found more frequent in CL/P and CP infant-parental triad cases compared to controls except for paternal rs7078160 rare homozygous allele.
    • This study gives a preliminary suggestion of GEI and is considered a valuable instrument for public health strategies

    Date of Award2015
    Original languageEnglish
    SponsorsKing Abdulaziz University
    SupervisorPeter Mossey (Supervisor)

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