Genetics and Recurrence
Text supplied by Salim Aftimos, Paediatric Geneticist, Starship Hospital
A cleft lip/palate is caused by the failure of developmental segments of the face to join up. The lip and palate are derived from the embryonic primary and secondary palates. The primary palate contributes to the lip, anterior tooth bearing gum region and the anterior part of the hard palate. The secondary palate contributes to the posterior hard and soft palates. The primary palate begins to form during the 4th week of gestation and the secondary palate begins to form from the 6th to 7th week of gestation. Formation of the upper lip and palate is completed by the 12th week of gestation. The primary palate is formed by fusion of the nasal and lateral maxillary processes. The secondary palate is formed from extensions of the inner side of the left and right maxilla which develop into palatal shelves and then fuse with each other and with the nasal septum. Failure of this orderly process of fusion of the primary or secondary palate will lead to clefting in the respective areas.
Statistically, around 1 in 700 babies are born with cleft lip/palate. While we know what happens we do not know exactly why. The general view is that it is a combination of genetic and environmental factors, which cause a child to be born with a cleft lip and/or palate.
Genetics of Cleft Lip and Palate
Cleft Lip (CL) and Cleft Palate (CP) may occur independently or together, and may be unilateral (one side only) or bilateral (both sides). In most children the cleft is an isolated malformation. In some, there may be associated malformations affecting other organs. These tend to occur more commonly with isolated cleft palates and least commonly with isolated cleft lips. In few children there may be a recognizable pattern of anomalies which denotes a “syndrome”.
A syndrome may be caused by a chromosomal abnormality where there may be either additional or deleted chromosomal material. A chromosome test is requested if this is suspected. The standard chromosome test does not identify if a tiny (submicroscopic) segment is missing. If there is a clinical suspicion, additional “FISH” tests may be requested to identify such a tiny segment. An example is the FISH test for the 22q deletion syndrome.
In some children or families cleft lip/palate may be caused by a single gene disorder. Genes are segments of DNA that code usually for certain cellular proteins and are scattered throughout our 23 pairs of chromosomes. There may be 30,000 or more of these genes. A mutation, which is a spelling mistake in a gene, may cause either familial forms of isolated CL/P, or syndromic forms of CL/P.
Familial forms of isolated CL/P may follow a dominant pattern of inheritance in which case the cleft may be passed on from one generation to the next. More rarely, there may be an X-linked pattern where female gene carriers may manifest milder or absent symptoms.
There are more than 300 syndromic forms of CL/P, most of them being very rare. These may follow dominant, X-linked or recessive patterns of inheritance. In a recessive situation, the affected child is the first to manifest the disorder in the absence of a family history, but there is a risk for subsequent siblings to be affected.
In most children born with CL/P however, the “cause” is termed “multifactorial”. This means there may be a small change in one or more of a number of CL/P susceptibility genes, which may interact with some environmental factors, such that a threshold is reached above which a cleft may be formed. Environmental factors may include maternal factors such as diabetes, intake of certain medications such as anticonvulsant drugs, or dietary factors (vitamin levels, alcohol, smoking), etc…
The recurrence risk for CL/P will depend on its classification, whether it is isolated, familial, syndromic, etc… In most cases where the etiology is multifactorial an empirical recurrence risk is offered. The figure is based on previous population studies of a large number of families. Such figures should be interpreted as reasonable guidelines, rather than precise measurements
March 18th, 2007 10:33
I am a Jamaican. I had a child (son) born with cleft palate(soft). He died. This was the first occurrence in both families. I am now pregnant for a different male. Is the chances of a cleft still great for my next baby. I am taking folic acid and prenatal vitamins.
May 16th, 2008 20:39
There are too many lies surrounding clefts. I believe the vast majority are inherited. Cover-ups by irresponsible sufferers in denial don’t tell their children the truth then that child marries. Their child then has a cleft baby. I doubt it has anything to do with the environment. It is probably 99% heriditary.
May 25th, 2008 15:24
@ Matt - perhaps you would care to do some actual research on the topic before posting a comment which serves no purpose other than showing the world you have no idea what you’re talking about.
It doesn’t take a rocket scientist to understand that if geneticists knew of any link they would have it sussed, and cleft lip/palate would no longer be an issue.
I would suggest you use the internet for something more basic . . . something that doesn’t involve too much thinking on your part - you obviously find it difficult.
July 20th, 2008 12:51
hi my daughter was born 15years ago with cleft lip and palate she has a family history of this she is the 6th one in my husbands family to have this the lip is single the same as 3 of the other family her grandfather, uncle, and great great grandfather had the double lip and palate. so I was wondering if I could get my daughter gene tested so she can be informed for when she has her children.
July 23rd, 2008 13:07
Hi Robyn
In New Zealand all cleft affected people are able to see a genetisit to help them with this. You can contact your local cleft centre and they will put you in touch with the right person.
Barbara
July 24th, 2008 22:07
Hi,
I had to terminate my 21 week old pregnancy because the ultra sound detected a bilateral cleft lip and palate. Please let me know what is the chance of this to recur and if there is any thing i can do to prevent the same in my future pregnancies. Thanks.
August 4th, 2008 16:05
There is no set rule as to whether or not you will have another cleft baby. It may seem daunting at first but having a cleft doesnt stop you having a great life - it is only a physical disability which can be fixed. If you are concerned you should check with a geneticist. But they cant guarantee you a “perfect”baby.
August 5th, 2008 11:55
SONIA:
Perhaps you didn’t have to terminate your pregnancy because of a cleft lip. Did you consider keeping your child, maybe putting it up for adoption…..for a chance at a REAL mothers love?? It wasn’t your baby’s fault it had a cleft lip/ palate. Don’t get pregnant again. Don’t put any child up to your unreasonable standards.
August 6th, 2008 22:41
Hi..
My name is Adil and my wife is now 24 weeks pregnant with our second child. Last week we did a 3D scan and we were informed that our child has a small cleft on the upper side of the left lip. I read over the internet that part of the cause is genetic, and only later I found out that my dad’s uncle had cleft lip (I didn’t get a chance to meet him since he passed away when my dad was still young).
Notwithstanding this, my wife and I remain positive and hope for miracle to happen between now and the delivery…
To be honest, I was disturbed by Sonia’s termination of her pregnancy, but that was her choice. For me and my wife, we promise ourselves that whatever happen, we will give unconditional love to our child as much as our first one…
Regards,
Adil Affandy Othman
adil_affandy@yahoo.com
August 20th, 2008 13:37
Wow, I hope that there was another reason why Sonia terminated her pregnancy. My son is 3 & 1/2 yrs old & was born w/a cleft lip & palate. He underwent surgery to repair & still has another surgery to go when he is 7-9 yrs old. He looks great & is the joy of our lives. When we mention something about it to people they are usually like, “What are you talking about, whats wrong w/his lip?” His surgeons did a fantastic job. At first it didnt look so great, but w/time it has come to look much better. We are currently expecting baby #2 & pray that we dont have to go thru that stress again, but we would do it all over again if we had to. I know there is speculation of enviornmental factors as well as genetics involved. There was no occurrrence of clefts in either of our families. However, I work in the dental field & about a year before I found out I was pregnant, a co-worker had a child born w/cleft lip & palate. This makes me wonder about enviornmental affects in the workplace on unborn children.
August 24th, 2008 16:03
Hi!
I have a son who was born with a cleft palate. I knew that something was wrong when he was born, but no one noticed until he was 2 months old. I said that his uvula was missing and a nurse told me that it would grown in? Very odd I thought. His pediatrician was like he has a cleft palate, and told me where to go to get help to fix it. The fact that when I left the hospital when I gave birth and no medical professional noticed irked me the most.
He just had his surgery on the 5th of August, and he is great. He also had tubes put in his ears since it affected his hearing and prior to his surgery he did wear a hearing aid.He went for hearing tests once a month to see if it got better. He still has a spot that is left that is taking longer to heal, but I wouldn’t change him for a thing in the world.
I am now 8 weeks pregnant, and after talking to numerous doctors/specialist, this cleft palate does not run on either side of the family and is a total fluke. They said that it was environmental and that since my son had no other symptom, like autism for example, that my next child has a 2 to 3% chance of having any other kind of cleft. If there was another symptom (near sighted) it would spike up to 50%.
To people who know that they are having a child with a cleft palate or lip. It will be stressful, but all you want in the end is for your child to be ok. Ethan is great and learning how his mouth works all over again. He is surprised with all the new sounds that he can make. He might need a speech therapist when he is older, but for the next year I will not have to worry about it. And it is only a 20% chance that he will need one.
So to all the parents, just be patient even though doctors appointments are stressful, in the end it is all worth it.