Cleft lip and palate causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Causes

During the first six to eight weeks of pregnancy, the shape of the embryo's head is formed. Five primitive tissue lobes grow:

a) one from the top of the head down towards the future upper lip;
b-c) two from the cheeks, which meet the first lobe to form the upper lip;
d-e) and just below, two additional lobes grow from each side, which form the chin and lower lip;

If these tissues fail to meet, a gap appears where the tissues should have joined (fused). This may happen in any single joining site, or simultaneously in several or all of them. The resulting birth defect reflects the locations and severity of individual fusion failures (e.g., from a small lip or palate fissure up to a completely malformed face).

The upper lip is formed earlier than the palate, from the first three lobes named a to c above. Formation of the palate is the last step in joining the five embryonic facial lobes, and involves the back portions of the lobes b and c. These back portions are called palatal shelves, which grow towards each other until they fuse in the middle.[1] This process is very vulnerable to multiple toxic substances, environmental pollutants, and nutritional imbalance. The biologic mechanisms of mutual recognition of the two shelves, and the way they are glued together, are quite complex and obscure despite intensive scientific research.[2]

The cause of cleft lip and cleft palate formation can be genetic in nature. A specific gene that increases threefold the occurrence of these deformities has been identified in 2004 as reported by the BBC.[3]

Environmental influences may also cause, or interact with genetics to produce, orofacial clefting. Scientists have investigated seasonal causes (such as pesticide exposure); maternal diet and vitamin intake; retinoids- which are members of the vitamin A family; anticonvulsant drugs; alcohol; cigarette use; nitrate compounds; organic solvents; parental exposure to lead; and illegal drugs (cocaine, crack cocaine, heroin, etc.) as teratogens that increase the possibility of clefting.

If a person is born with a cleft, the chances of that person having a child with a cleft, given no other obvious factor, rises to 1 in 14. Research continues to investigate the extent to which Folic acid can reduce the incidence of clefting.

In some cases, cleft palate is caused by syndromes which also cause other problems. Stickler's Syndrome can cause cleft lip and palate, joint pain, and myopia. Loeys-Dietz syndrome can cause cleft palate or bifid uvula, hypertelorism, and aortic aneurysm. Cleft lip/palate may be present in Patau’s Syndrome (trisomy 13). Many clefts run in families, even though there does not seem to be any identifiable syndrome present.

Maternal drug use - Clomifene

References

  1. Dudas et al. (2007): Palatal fusion – Where do the midline cells go? A review on cleft palate, a major human birth defect. Acta Histochemica, Volume 109, Issue 1, 1 March 2007,1-14
  2. Dudas M, Li WY, Kim J, Yang A, Kaartinen V (2007). "Palatal fusion -where do the midline cells go? A review on cleft palate, a major human birth defect". Acta Histochem. 109 (1): 1–14. doi:10.1016/j.acthis.2006.05.009. PMID 16962647.
  3. "BBC NEWS". Retrieved 2007-07-01. Text " Cleft palate genetic clue found " ignored (help); Text " Health " ignored (help)



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