Wide Smiles: Cleft lip and cleft palate support

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What Happened?!


A Look at the Causes of Clefting
Clefts commonly have a genetic basis, although occasionally drugs taken during pregnancy can be involved. Clefts of the lip and palate can run in families and be due to a single gene. If the gene is transmitted from one affected parent to their offspring, then it is generally considered to be dominant. If neither parent is affected, then the gene could be recessive, and would require that both parents contribute the same recessive gene to their affected child. In the latter case, a clear inheritance pattern may not exist. This is indistinguishable from a "susceptibility" or "multifactorial" model which is the basis of the assessment of recurrence risk used by geneticists for parents who already have a child with a cleft. This is based upon surveys of large numbers of cleft lip/cleft palate families.

Unaffected parents with an affected child, according to this model, have an approximately 5% chance of having another similarly affected child. This risk increases if the couple have more than one affected child. In dominant inheritance, the risk of recurrence is 50%, and in recessive inheritance it is 25%. These are both higher than the multifactorial model, but the risk does not change with each pregnancy, regardless of the outcome.

In some cases. cleft lip and/or palate may be associated with a syndrome. A syndrome is a collection of physical findings which run together in the same person, and for the most part are seen in all individuals who have that syndrome. Syndromes are more common in cleft palate alone than in cleft lip with or without cleft palate, but can occur in any of these. Syndromic clefts are commonly inherited as single gene defects. but can be due to abnormalities in the baby's chromosomes, to something used during pregnancy or of a sporadic nature. Single genes have already been discussed, but of importance is to note that those characteristics of a syndrome that run in a given family may be a good indicator of a risk for a cleft, but a cleft may not always occur. Some syndromes may only have a 30% risk for an associated clefs for example, which means that 70% of the time many other characteristics of the syndrome may appear, but without a cleft.

Chromosomes are the spaghetti- like structures in a cell that contain DNA. DNA is the gene material which directs cell function and is handed on from parent to offspring as genes. Abnormalities of chromosomes in this sense are also "genetic" abnormalities, but they may or may not be inherited. Extra chromosomes, small missing pieces of chromosomes (deletions), duplication of areas, etc., may all affect loci (locations of genes on the chromosome) involved with the cleft palate syndrome.

Babies with cleft lip and cleft palate who have several other abnormalities also present almost always have their chromosomes tested (karyotyping). Normal girls have a 46XX karyotype, and boys have a 46XY karyotype. This says that they have 46 (23 pairs) of chromosomes in each cell, with two of these being X chromosomes in girls, and in boys one is an X and another is a Y. Analysis of chromosomes to find the exact location of genes upon them is of considerable importance if we are to better understand clefting disorders in the future. Currently a major effort is being carried out to map all the gene loci on these chromosomes. Specific DNA markers may help geneticists in the future give families more accurate estimates of their risk for recurrence of cleft lip and palate by performing DNA testing.

Substances used during pregnancy rarely seem to cause cleft lip and cleft palate. Those known to do this are alcohol, Dilantin (a seizure medication) and excess of vitamin A. Parents should not search for reasons to blame themselves for "causing" a cleft lip or cleft palate because it is not their fault. Many factors can contribute to anyone using drugs during their pregnancy and may not have left the parent much choice. Cleft lip and cleft palate occur early in a pregnancy-- often before a mother is aware she is pregnant. The ideal approach to pregnancy is to plan for a child, seek early prenatal care and avoid any nonessential medications or recreational drugs. Only substances taken by the mother seem to affect the development of the offspring, but very little is documented about the affect of drugs on the reproductive system of the father.

Of importance to any family who has a child with a cleft of any kind is a visit to the medical geneticist. The geneticist will take a good family and prenatal history and examine the child and his/her family either personally or from photographs and order a chromosome test or other evaluations as necessary. Depending on the information obtained, the geneticist will then be able to advise the parents of the "cause" of the clefts and give estimates of its recurrence in future pregnancies for all family members. Geneticists are now commonly involved with many craniofacial teams nationally because their diagnostic skills add considerably to the management of that child in the team as well as providing support and advice to the parents of a team patient. Dr. Andrew Poole, DDS, PhD, is the Director of the Craniofacial Disorders Team at the University of Connecticut Health Center. He is also the Genetics Consultant on the staff of WIDE SMILES.

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