Environmental Interaction
Craniofacial disorders have high variance in phenotypic expression, and researchers have suggested this variance could be due to interactions between the mutated/deviated genes and other genes, along with interactions with environmental factors. Environmental causes have been found to contribute to craniofacial clefting, however, these are still influenced by and supported by genetic factors. Many studies, for example, have linked maternal smoking to increased CLP risk; however, the increased risk suggests that genes in metabolic pathways could still contribute to susceptibility or formation of CL/P. Development and Inheritance
The craniofacial complex begins its progress in the fourth week of development, and results from neural crest cells migrating to form and fuse the facial primordia. Failures or deviations in this process result in craniofacial clefts, either CL or CP. The range of variation in phenotype aligns with ancestry. Studies have found increased amounts of clefting in the relatives of patients with clefts, suggesting genetic factors are the underlying cause for CL/P. Inheritance has a known and significant role in human craniofacial morphology. This is supported through cephalometric and anthropometric comparisons of family members including between triplets, twins, siblings, and parents and children. Genetic Experimentation
Genetic factors of craniofacial clefting can be investigated and tracked through several methods including sequencing in humans, Genome-wide association studies (GWAs), fate mapping, expression analysis, and animal studies (knockout experiments or models with clefting from chemical mutagenesis). Twin studies and familial clustering have also revealed that facial structure and formation are genetically linked.
In this plan, a difference is made between problems that need to be solved to improve the health of the patient (coloboma) and problems that need to be solved for a better cosmetic result (hypertelorism). The treatment of the facial clefts can be divided in different areas of the face: the cranial anomalies, the orbital and eye anomalies, the nose anomalies, the midface anomalies and the mouth anomalies. Treatment of the cranial anomalies
The most common cranial anomaly seen in combination with facial clefts is encephalocele. Encephalocele
The treatment of encephalocele is based on surgery to repair the bony gap and provide adequate protection of the underlying brain. The question remains if the external brain tissue should be put back into the skull or if it is possible to cut off that piece of brain tissue, because its claimed that the external piece of brain tissue often isn’t functional, with the exception of a basal encephalocele, in which the pituitary gland can be found in the mouth. Treatment of orbital / eye anomalies
The most common orbital /eye anomalies seen in children with facial clefts are colobomas and vertical dystopia. Coloboma
The coloboma which occurs often in facial clefts is a cleft in the lower or upper eyelid. This should be closed as soon as possible, to prevent drought of the eye and a consecutive loss of vision. Vertical orbital dystopia
Vertical orbital dystopia can occur in facial clefts when the orbital floor and/or the maxilla is involved in the cleft.