**9. Conclusion**

OFCs are the most common craniofacial anomalies, and one of the most common congenital anomalies worldwide. OFCs have historically been grouped as CL/P or CPO. However, existing evidence suggests that separate etiologies may exist for cleft lip alone versus cleft lip with palate. CL/P and CPO are classified as syndromic or nonsyndromic; nonsyndromic cases are further subclassified as multiple or isolated.

Both genetic and environmental factors have been implicated in the etiology of OFC. The genes underlying a number of known syndromes associated with OFC have been identified. Furthermore, environmental factors such as alcohol and tobacco have been shown to modulate the risk of OFC conferred by certain genetic factors.

Although nonsyndromic OFCs are not traditionally the subject of genetic analysis, a number of genomic association studies have evaluated the link between genetic variants and nonsyndromic OFC. Examples of genes that have been examined in such studies include those that code for growth factors, transcription factors, and nutrient metabolism proteins. In addition to genetic factors, studies have recently begun to explore the role of epigenetic modifications in palatal ontogeny and etiology of OFC.

A number of environmental and maternal factors that influence the risk of having a child with OFC are well-described. In particular, family history, maternal drug use, nutrition, and exogenous exposures demonstrate strong links with development of OFC in the child.

Several studies have shown a higher incidence of cancer amongst patients with CL/P and their families. Additionally, studies have begun to identify higher rates of CL/P in the families of patients with cancer, although less is known about this. Combined, these suggest that CL/P and cancer may be mediated by shared environmental and genetic etiologies.
