KNUST Research Week and Scientific Conference: Empowering Researchers to Achieve Impactful Outcomes

Background: Craniofacial microsomia (CFM) is the third most common congenital craniofacial anomaly after orofacial clefts (OFCs), characterised by asymmetry of the face and underdevelopment of facial structures due to defects in the first and second pharyngeal arch derivatives. Irrespective of its clinical significance, the genetic basis of CFM remains poorly understood, particularly in African populations where research is limited. This study sought to investigate the genetic architecture of CFM in a Ghanaian cohort.
Methods: Seven families, each comprising one affected proband and their unaffected parents, were recruited from the National Cleft Care Center (NCCC) at Komfo Anokye Teaching Hospital (KATH), Ghana. Clinical deep whole exome sequencing (WES) was carried out at 100X, followed by variant calling using the Sentione workflow. Pedigree analysis and variant prioritisation were performed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Maternal environmental risk factors were assessed through structured questionnaires. Functional annotation, pathway enrichment, and protein–protein interaction (PPI) network analyses were undertaken using g:Profiler, STRING, and Cytoscape.
Results: Multiple candidate variants were identified, including novel de novo and rare variants in PAX6, FOX4DL3, EIF3C, EIF3CL, PRDM9, RUNX1, SAMD1, and KCNMA1. Several of these genes are associated with neural crest cell (NCC) migration, cell adhesion, and craniofacial development. PPI analysis highlighted hub genes such as PRDM9, PAX6, SAMD1, and RUNX1, underscoring their potential regulatory role. Environmental exposures, including maternal folate deficiency, herbal remedy use, consanguinity, and contact with lead-containing products, were also reported, suggesting possible gene–environment interactions.
Conclusion: This study presents the first-ever genetic investigation of CFM in a Ghanaian cohort, providing novel insights into candidate genes and environmental influences. The findings highlight the importance of ancestry-specific research to improve understanding of aetiology, diagnosis, and counselling for craniofacial anomalies in underrepresented populations.