Identification of Possible Maternal Risk Factors for Development of Syndromic Oro-Facial Clefts

Coelette Smit,Kurt-Wilhelm Bütow,Steve Olorunju,Sharan Naidoo

doi:10.11648/j.cnn.20190303.11

Abstract

Context: The concept “epigenetics” highlights that environmental factors are able to trigger changes in gene activity. This confounds the search for aetiological factors of syndromic oro-facial clefts as it interplays between genetics and environmental stimulation. Subjects and Methods: The study makes use of a database of syndromic cleft patients over 33 years at the Department of Maxillo-Facial and Oral Surgery at the University of Pretoria. The ten most common clefting syndromes (Fairbairn-Robin triad, Demarque van der Woude syndrome, Holoprosencephaly, Naso-maxillo-acro dysostosis (Binder’s syndrome), Goldenhar syndrome, Treacher-Collins syndrome, Trisomy 13 (Patau’s syndrome), P63 Mutation associated clefting disorders, Trisomy 21 (Down’s syndrome), Oro-Facial Digital syndromes) were included amounting to 517 patients. The nine most common maternal risk factors (Unknown Infection, Viral Infection, HIV, Medication, Smoking, Alcohol, Oligohydramnios, Vitamins, Hormones) were included totaling 398. Results: Fairbairn-Robin triad had a significant correlation with oligohydramnios, infection and medication. Demarque-van der Woude syndrome presented with a significant contribution from medication and Holoprosencephaly showed a significant correlation with vitamin supplementation. Conclusion: based on the results of this study Fairbairn-Robin triad appears to have a strong environmental component to the presentation thereof. Demarque-van der Woude was indicated to having a genetic-environmental interplay contributing to the presentation of the syndrome.

Highlights

James Paget wrote in the Lancet (1882) that curiosities or changes could become the beginning of excellent knowledge
According to the literature about 70 percent of cases with cleft palate (CL/P) and 50 percent of cleft palate (CP) are non-syndromic. [3, 4] both CL/P and CL result in malformation of the midface, they differ in the context of embryology, etiology, associated abnormalities, candidate genes, and recurrence risk. [5]
Six results proved to be significant; for Fairbairn-Robin triad; Unknown Infection had a P-value of 0.032 with a 95% CI [0.923, 0.186]; Viral infections for Fairbairn-Robin triad with a P-value of 0.0009 with a 95% CI [0.109, 0.208] and lastly for Fairbairn-Robin triad; Medication with a P-value of 0.000 and a 95% CI [0.318, 0.451]

Summary

Introduction

James Paget wrote in the Lancet (1882) that curiosities or changes could become the beginning of excellent knowledge. There remain many unanswered questions regarding the aetiopathogenesis of syndromic oro-facial cleft disorders. Chromosomal aberrations are the most common cause of oro-facial clefts and is followed by Mendelian / heterogenous abnormalities and teratogenic factors. [2] The oro-facial cleft includes cleft lip with or without a cleft palate (CL/P) or as an isolated cleft palate (CP), these abnormalities may be syndromic/genetic disorders or nonsyndromic. [3, 4] both CL/P and CL result in malformation of the midface, they differ in the context of embryology, etiology, associated abnormalities, candidate genes, and recurrence risk. The study of fetal midfacial anomalies has led to the detection of candidate genes and the recognition of environmental factors that affect fetal development. Coelette Smit et al.: Identification of Possible Maternal Risk Factors for Development of Syndromic Oro-Facial Clefts According to the literature about 70 percent of cases with CL/P and 50 percent of CP are non-syndromic. [3, 4] both CL/P and CL result in malformation of the midface, they differ in the context of embryology, etiology, associated abnormalities, candidate genes, and recurrence risk. [5]

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Discussion

Conclusion