The biologic mechanisms of mutual recognition of the two cabinets, and the way they are glued together, are quite complex and obscure despite intensive scientific research.Orofacial clefts may be associated with a syndrome (syndromic) or may not be associated with a syndrome (nonsyndromic). Syndromic clefts are part of syndromes that are caused by a variety of factors such as environment and genetics or an unknown cause. Nonsyndromic clefts, which are not as common as syndromic clefts, also have a genetic cause. Genetics
Genetic factors contributing to cleft lip and cleft palate formation have been identified for some syndromic cases. Many clefts run in families, even though in some cases there does not seem to be an identifiable syndrome present. A number of genes are involved including cleft lip and palate transmembrane protein 1 and GAD1, One study found an association between mutations in the HYAL2 gene and cleft lip and cleft palate formation. Syndromes
The Van der Woude syndrome is caused by a specific variation in the gene IRF6 that increases the occurrence of these deformities threefold. Mutations in interferon regulatory factor 6 (IRF6) that cause cleft lip palate are also implicated in neural tube defects such as spina bifida. Another syndrome, Siderius X-linked intellectual disability, is caused by mutations in the PHF8 gene (OMIM: 300263); in addition to cleft lip or palate, symptoms include facial dysmorphism and mild intellectual disability.In some cases, cleft palate is caused by syndromes that also cause other problems:

Stickler syndrome can cause cleft lip and palate, joint pain, and myopia.
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The term orofacial cleft refers to either condition or to both occurring together. These disorders can result in feeding problems, speech problems, hearing problems, and frequent ear infections. Less than half the time the condition is associated with other disorders.Cleft lip and palate are the result of tissues of the face not joining properly during development. As such, they are a type of birth defect. The cause is unknown in most cases. Risk factors include smoking during pregnancy, diabetes, obesity, an older mother, and certain medications (such as some used to treat seizures). Cleft lip and cleft palate can often be diagnosed during pregnancy with an ultrasound exam.A cleft lip or palate can be successfully treated with surgery. This is often done in the first few months of life for cleft lip and before eighteen months for cleft palate. Speech therapy and dental care may also be needed. With appropriate treatment, outcomes are good.Cleft lip and palate occurs in about 1 to 2 per 1000 births in the developed world. Cleft lip is about twice as common in males as females, while cleft palate without cleft lip is more common in females. In 2017, it resulted in about 3,800 deaths globally, down from 14,600 deaths in 1990.