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You'll find hundreds of files on cleft lip, cleft palate here on widesmiles.org.
This one is about: Genetic Information and Clefts
(c) 1996 Wide Smiles
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GENETIC INFORMATION AND CLEFTS:
New Horizons in Understanding and Prevention
by Dr Jeffrey Murray
Cleft lip and/or palate is an easily recognized, yet complicated disorder with
important implications for normal nutritional, dental, speech, hearing and
psychological development. A majority of cases of clefting are referred to as "nonsyndromic". That means they lack an association with other features commonly
found in so-called syndromes. Although statistical analysis of such non-syndromic
cases of clefting suggests that genetics plays a strong role in these, it is likely there
are different causes, including not only genetic factors, but also environmental and
random ones as well.
Syndromic forms of clefting, or those associated with other abnormalities, are also
caused by a variety of different factors. There are, in fact, more than 300 known
disorders that can involve clefting, with a number of others involving abnormalities
of the development of the facial regions. A large number of these have also been
identified as being caused by genetic factors. Environmental agents (i.e., drugs,
infections, etc) as well as a variety of unknown causes also play a role in this group.
As a result, talking about the genetics of cleft lip and palate can be a daunting
undertaking.
Human genetic material is made up of a series of components which can be broken
down at several different levels. Most of the cells of the body contain packages of
genetic material called chromosomes. Each chromosome contains approximately
1,000 genes. Each gene is a specific set of instructions to carry out a specific
function of the body. Genes control everything from muscle proteins and the
oxygen-carrying molecule hemoglobin, to the determinants of hair and eye color.
Each gene is comprised of several thousand base pairs of the molecule,
DNA (Deoxyribonucleic Acid). DNA is made up of four independent
chemical structures referred to as mic;eptodes (commonly thought of as the
letters of the DNA alphabet: A, G, C, or T). An abnormality in even one of
these letters can result in enough damage to the inherited material that a significant
birth defect, such as a cleft lip or palate, can arise. The entire set of chromosomes
contains approximately three BILLION such nucleotides, or letters. Understanding
the nature and position of each one of these individual nucleotides presents a
challenging goal for science in an attempt to obtain a complete understanding of
the human inherited material.
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Substantial progress has been made in understanding the nature and position of
many different genes and several hundred thousand different nucleotides, but an
enormous amount of work is still ahead for a complete understanding of this
genetic material. Each of the possibly several hundred different genetic causes of
cleft lip and palate may be underlined by different changes in the basic DNA
structure. Therefore, the problem of understanding the nature each individual form
of cleft lip or palate can take is, again, an extremely difficult one. It is nonetheless
underway in many of the laboratories around the world.
In recent years, sophisticated techniques of molecular biology, coupled with
improved statistical analysis have allowed physicians, scientists, genetic
counselors, developmental biologists and others to gain insight into at least some
of the genetic causes of clefting. Several different approaches have been used,
including those that involve detailed studies of families that contain more than one
individual with cleft.
Information developed form studies of animal models suggests a group of so-called
candidate genes that may play a role in normal facial development. These
candidate genes can then be studied in greater detail as we look for evidence of
specific genetic rearrangements that may underlie disturbances in the normal
process of facial development.
The long range goals of such studies are several fold. These goals
include obtaining a better understanding of not only the abnormal
developmental process, but the normal process as well. A better understanding of
the specific genetic factors involved in such processes will hopefully lead
to improvements in the ways in which cleft lip and palate may be
potentially prevented. For example, it has recently been demonstrated that a
usually unrelated birth defect called spina bifida can in some cases have
its recurrence risk in families decreased by the use of appropriate
vitamin supplementation in the pregnant mother. While as yet there is not confirmed
evidence that such vitamin supplementation will play a role in preventing
occurrences of cleft, it is hoped that by obtaining a better understanding of the
development of the face, we will be better able to identify such factors and target
ways to then prevent or decrease the occurrence of clefting disorders.
A second, more immediate goal of such projects is to obtain improvements in our
ability to identify the specific genetic components of the many different forms of
clefting with the hope that identification of these factors will lead to an improvement
in our ability to identify individuals at risk of having a child with a cleft, and to
provide those individuals with better information about what the risks are, and how
they can then best plan their families in light of a better known and specific risk. In
the last several years, progress has been made using these techniques in a variety
of inherited disorders, which significant breakthroughs being made in either
localizing the genes causing these disorders to specific chromosomes, or
identifying the specific gene on a chromosome involved in a particular disorder.
some of these successes have been reported in the area of cleft lip and palate and
craniofacial development.
---------------------------------Dr Jeffrey Murray is a pediatrician, clinical geneticist and
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molecular biologist with an interest in the molecular genetics of human craniofacial
development. Besides working with families who have children with cleft lip and
palate in the US and overseas, he has a laboratory effort to understand genetic
components of Van Der Voude Syndrome. He is a member of the Department of
Pediatrics at the University of Iowa.
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