This booklet on Treacher Collins syndrome was written by Elsa Reich, M.S., who is a genetic counselor and Clinical Assistant Professor of Pediatrics at New York University School of Medicine. In addition, she is the genetic consultant for the multidisciplinary craniofacial team associated with the Institute of Reconstructive Plastic Surgery at NYU Medical Center, which is directed by Joseph McCarthy, M.D.
While the emphasis in this booklet is on the genetic aspects of Treacher Collins syndrome, other information about the disorder is also included. However, this is not an all-inclusive text on the multidisciplinary aspects of the syndrome. All the information presented is current as of the date of printing. Some information about Treacher Collins syndrome is still unknown, and therefore not addressed in this booklet. Addenda to this booklet will be available as advances are made in the disciplines which serve patients with Treacher Collins syndrome.
If, after reading the material presented, you find that your questions are still unanswered, we strongly encourage you to address your concerns and questions with your professionals. We at the Treacher Collins Foundation are eager to know if this booklet has been helpful. Feel free to send your comments to: Hope Charkins, M.S.W., Executive Director, Treacher Collins Foundation, P.O. Box 683, Norwich, VT 05055, U.S.A.
WHO WAS THIS BOOKLET WRlTTEN FOR?
You may be a parent who has just been told that your newborn baby has Treacher Collins syndrome. You may be the confused parent of an older child with Treacher Collins syndrome and want more information. You may also be an adult or teenager wanting to know more about your own condition. This booklet is designed for all of you. You will find information about the condition, its cause and its treatment. Not all of the questions will apply to all of you. Pick and choose what is helpful.
From the moment I heard that my pregnancy test was positive, I started to dream about a little boy in a sailor suit with luxuriant dark curly hair like my husband’s. I wondered who he would resemble. When my son was born and given to me to hold, I immediately noticed that he had dark hair, but it was not curly. I did not notice his facial difference until the doctor came into the recovery room to break the news. My husband nervously paced the floor while he listened to the details. I was still feeling euphoric after the birth, however, and naively asked if the problems could be fixed. The doctor’s answer was not very positive or reassuring. More than three months passed before my son was evaluated at a craniofacial center and I learned that the information given to me that day was not accurate. The correct answer to my question was, “Yes, your son’s problems can be fixed, but his hair still won’t be curly.”
Of course, this was not all I learned in the months following my son’s birth. I also learned that having a child born with a facial difference is not something you learn to cope with overnight. You need time to think about what has happened and how you feel about it; you need information about your child’s condition and what can be done to help her; and you need to find support wherever you can – from family, friends, professionals, other parent of kids with facial difference, and support groups. Perhaps most importantly, I learned that my son was more like other babies than unlike them. (reprinted with permission from Children with Facial Difference: A Parent’s Guide, by Hope Charkins, M.S.W., Woodbine House, 1996, p. 50-51.)
What Is Treacher Collins syndrome?
Treacher Collins syndrome is a hereditary condition that primarily affects the structures of the head and face. Individuals with this condition have a characteristic appearing face. The physical features include: downslanting eyes; notches of the lower eyelids, most frequently on the 1/3 of the lid furthest from the nose; underdeveloped cheekbones; prominent nose; broad mouth; small chin with a steep angle of the lower jaw; underdeveloped, malformed and/or prominent ears; and “sideburns” (licks of hair extending in front of the ears.) Individuals with this condition frequently, but not always, have some degree of hearing loss, usually conductive. The nasopharynx may be narrow. There are other problems that are more frequent in people with Treacher Collins syndrome than in the general population, but occur only in a minority of affected individuals. These problems include: cleft lip, with or without cleft palate; cleft palate alone; heart defects; and, strabismus. Children and adults with Treacher Collins syndrome are usually normal individuals with some physical abnormalities of the face.
Are there any other names for Treacher Collins syndrome?
The two most common alternative names are “mandibulofacial dysostosis” and “Franceschetti-Klein Syndrome”. Treacher Collins and Franceschetti and his co- workers were doctors who described patients with this characteristic appearance in 1900 and 1949 respectively. “Mandibulofacial dysostosis” is the name Dr. Franceschetti gave to this condition, and simply means that there is abnormal development of the lower jaw (mandible) and the face.
Are there abnormalities that can be identified on x-rays?
The skull of an individual with Treacher Collins syndrome is usually normal. The boney ridges above the eyes are usually underdeveloped, as are the bones of the cheeks (malar bones). The malar bones may be completely absent, but more frequently are malformed and underdeveloped. In fact, there frequently is failure of fusion of the zygomatic arches (the aspects of the malar bones which form the prominence of the cheek). There are other variations affecting the sinuses, orbits (eye socket) and mastoids. The lower jaw is usually short and, rather than being in an almost horizontal orientation, is seen to assume a steep angle in relation to the rest of the face. Even in a mildly affected individual, there is a small notch, the so-called “antegonial notch”, that is seen on the lower edge of the lower jaw about one-half to two-thirds of the way up from the chin.
What are the more specific findings in the eyes?
The corners of the eyes slant downward because of the poor development of the underlying bony structure of the face. On the part of the lid closest to the nose, next to the “notch,” there are sometimes no eyelashes. The iris may also have a “notch,” but this is less common. Vision is usually unaffected. Affected individuals may have strabismus (the eye/s turning in) and may require glasses, but this does not differ significantly from unaffected people.
How does Treacher Collins syndrome affect intelligence?
Most of the people with Treacher Collins syndrome have normal development and intelligence. There may be a slightly increased incidence of developmental delay among individuals with Treacher Collins syndrome, but it is not clear whether the apparent delay is real or perhaps related to hearing loss. Hearing loss should be detected as early as possible in order to permit the development of speech.
Children without any physical abnormalities also sometimes have developmental delays. When a child with Treacher Collins syndrome has developmental delays, it may be related to the syndrome, but it is not always clear that this is so. It also may be related to lack of oxygen in a newborn if there is a serious respiratory problem. Infants with this condition can be expected to do all the things that other infants do. Just as all infants do things at slightly different times, so do infants with Treacher Collins syndrome. Children with Treacher Collins syndrome go to regular schools and can be expected to get the same advanced education as anyone else. REMEMBER: Let your child show you what he/she can do!
Do all affected individuals show all the signs of Treacher Collins syndrome?
Treacher Collins syndrome is a highly variable condition. Some individuals are affected with severe manifestations of many of the typical features and others may be so mildly affected as to have escaped diagnosis. Some parents who were never aware that they were mildly affected may be diagnosed after the birth of a severely affected child. A mildly affected individual has the possibility of having a severely affected child and therefore all close relatives should be carefully examined.
Do all affected individuals “look alike”?
Individuals with Treacher Collins syndrome resemble one another, but each has his or her own unique characteristics, because, after all, each person is made up of thousands of genes, not just the Treacher Collins syndrome gene. Those other genes also influence appearance. Hair color, height, etc., are inherited and may be more like the parents’. Just as the face of any individual changes from infancy to childhood, so does the face of those individuals with Treacher Collins syndrome.
Can I tell how my child will look by seeing affected adults or photographs of affected adults?
While your child will resemble other individuals with Treacher Collins syndrome, any particular adult with Treacher Collins syndrome will not necessarily reflect the way your baby will look. It is not always helpful to compare the appearance of your new baby or yourself with that of other affected individuals. Think about how it would be for the parent of any newborn baby to see pictures of the way he or she will look as an adult! We have little way to know how a child will look as an adult. Some are fat, some thin, some with hair, some without, some attractive, some quite homely. The point is, that as parents and family members, we love those adults because they are our children. We become used to our own appearance and are not so aware of how it changes. We become used to our own child’s appearance and don’t always realize how that child changes. Each affected child/individual will develop and change in his/her own way, just as any other child/individual will. Of course, some individuals are more or less affected than others. Some have had extensive reconstructive surgery, some little. As an adult, even though you or your child may resemble other affected individuals, no one person will look exactly like you or your child.
Most important to remember is that a picture is not a living person. We don’t see people just in terms of the way they look. We see them as a whole, as a personality–the way they talk, laugh, and respond. A picture doesn’t do any of those things. Many times the person looks alot better than his/her picture.
Are there any health problems associated with Treacher Collins syndrome?
Because the pharynx and the nasal passages are narrow and the jaw small, children with Treacher Collins syndrome may have difficulty breathing, especially at night. This is called “sleep apnea.” If your child wakes frequently during the night, turns blue or dusky at any time, or has difficulty breathing, call the doctor and have the child evaluated. You may have to arrange to have a special monitor hooked up to the child at night. Breathing problems are most significant in the infant and may be a problem during surgery. Breathing problems should improve with age and/or after surgical intervention. Some children may require a tracheostomy (a tube in the throat to aid breathing). Some children have feeding problems. Another health problem which has already been mentioned is hearing. Many individuals with Treacher Collins syndrome have some degree of hearing loss. It is quite variable and should be detected as early as possible and managed appropriately with hearing aids.
What is the cause of Treacher Collins syndrome?
Treacher Collins syndrome is a genetic condition. A genetic condition is caused by the presence of one or more genes that are either not working at all or not working as they should. Genes are the smallest units of hereditary information and may be thought of as a blueprint or “code” for everything that takes place in the body. Genes are passed from generation to generation, from parent to child, in the egg of the woman and the sperm of the man. Genes occur in pairs, and everyone has thousands of different gene pairs. Treacher Collins syndrome is caused by a change in a gene which influences facial development. This changed gene may be inherited from a parent affected with Treacher Collins syndrome or it may arise anew in either the egg or the sperm of an unaffected parent.
What is the pattern of inheritance that is operating in Treacher Collins syndrome?
Treacher Collins syndrome is a condition that requires only one gene of a pair to be non-working in order for the condition to become apparent. This pattern of inheritance is called “dominant”. Dominantly inherited conditions usually affect males and females equally.
How does dominant inheritance work?
Hereditary conditions are passed from parent to child in the egg and/or sperm cells. These cells are produced in such a way that the number of genes is reduced to one half the original number, one gene of each pair, so that at the time of conception the baby receives one gene of each pair from each parent.
From the diagram below, one can see that there are two possible outcomes for each pregnancy. An affected individual makes two kinds of cells, one carrying the working gene, and one the non-working or Treacher Collins syndrome gene. There are then two possible outcomes of the conception. An affected individual has a 50% chance of having an unaffected child and a 50% chance of having a child with Treacher Collins syndrome. These chances apply to each and every pregnancy. The outcome of one pregnancy does not influence the chances in the next pregnancy. Just because this baby was affected does not mean that the next one won’t be. What this means is that anyone who is carrying the gene for Treacher Collins syndrome has a 50:50 chance of having an affected child and a 50:50 chance of having an unaffected child
Why do we have a child with Treacher Collins syndrome when neither of us is affected?
There is an affected parent in only about 40-50% of the families with an individual with Treacher Collins syndrome. In addition, there may be other affected family members. In the remaining families, there is no other affected person. When there is no one else in the family with Treacher Collins syndrome, this condition has occurred as the result of a new “mutation”.
What is a mutation?
A mutation is a permanent change or alteration that takes place in a gene which can neither be prevented nor predicted. Mutations are naturally occurring events that take place in all living things. They may be helpful, harmful or neutral. A mutation has occurred in the egg cell or in the sperm cell from which the affected individual was conceived. The parent in whose cell this mutation occurred is normal and healthy and has no way of knowing that it has happened. There is nothing in the medical or pregnancy histories of these parents that gives us a clue about why this has happened. We cannot identify the cause in individual families.
There are some dominantly inherited conditions in which there is an association of new mutations with advanced paternal age. This has been demonstrated in Treacher Collins syndrome, but not as strongly as in other disorders. There are many young couples who have a child with Treacher Collins syndrome that has occurred as the result of a new mutation.
Did we/our parents do anything during the pregnancy to cause our child/me to have Treacher Collins syndrome?
We can answer that question with a resounding “NO”! Remember that Treacher Collins syndrome is caused by a non-working gene that is present at the time of conception. The “program” is already in the works. Nothing that has happened during the pregnancy causes anyone to have Treacher Collins syndrome. Nothing that either parent has done, such as standing in front of a microwave oven or working at a video display terminal before or during the pregnancy, caused Treacher Collins syndrome. There is no evidence that past use of recreational drugs by either parent is a cause. No one is responsible.
Has the gene for Treacher Collins syndrome been found?
Yes. It is a gene on chromosome #5 that investigators call “Treacle.” An alteration or mutation in this gene has been found in many families/individuals with Treacher Collins syndrome. Thus far, almost every family has a different mutuation. Therefore, the entire gene must be scanned to find the alteration in each family and this currently takes quite a long time, usually several weeks. It is possible that there will be some families for whom an alteration will not be found immediately.
What kind of test will be done on me to identify the mutation?
A simple blood test.
Who should be tested?
The individual who is affected with Treacher Collins syndrome.
How does a parent or other relative know whether he/she is affected?
If you are the parent or close relative of a person with Treacher Collins syndrome, you should consult with a geneticist to find out if you may be mildly affected. A careful examination by a knowledgeable specialist may be adequate to determine whether you are affected. The geneticist may request x-rays, hearing and other tests. However, there are some individuals whose symptoms are so subtle that a physical exam alone may not be sufficient to determine with certainty whether they are affected. The geneticist may suggest a DNA test be done that will allow him/her to determine if you have the mutation causing Treacher Collins syndrome.
How can I find out if I have the mutation causing Treacher Collins syndrome?
Under most circumstances the affected individual/s in your family should be tested first. If a mutation is identified in an affected individual in your family and you do not have the mutation, you know with certainty that you are unaffected. If an affected individual in your family is not available for testing, and no mutation is found in you, it will not be possible to determine with certainty whether no mutation was found in you because you are unaffected, or because a mutation in the affected family member was not identifiable. Therefore, it is always preferable to identify the mutation in your affected family member first.
What is the chance of an unaffected parent having a second affected child?
If both parents of an affected individual are unaffected, the chance of having a second affected child is relatively small. It is slightly greater than that of other people because it is biologically possible for a person who is unaffected to have a group of cells (eggs or sperm) which carry the gene for Treacher Collins syndrome. This is called “germline mosaicism”. We cannot estimate what percentage of the total cells these “Treacher Collins syndrome cells” might be, and therefore it is not possible to know what the specific risk of recurrence is; however, we know from our studies that the birth of a second affected child to unaffected parents is rare. A geneticist may give you a specific risk figure for recurrence when you are both unaffected, but it is not possible to know exactly what your chance might be. IMPORTANT: The vast majority of unaffected parents with an affected child have only one affected child.
What is the chance for my unaffected children/brothers/sisters/other family members to have an affected child?
If your relatives are unaffected, they have no greater chance of having a child with Treacher Collins syndrome than anyone else in the general population. Again, any relative of an individual with Treacher Collins syndrome should be seen by a geneticist to determine whether he/she has any signs of Treacher Collins syndrome.
Does Treacher Collins syndrome get worse with each succeeding generation?
Experts used to think that this was so, but this has not been clearly demonstrated. It is probable that this finding is a result of the bias of ascertainment. Before surgery was so extensively utilized, severely affected individuals were less likely to marry and have children, primarily for social reasons. Therefore, the people who did marry were the less severely affected individuals who, in many cases, were not diagnosed until after the birth of a more severely affected child. It looked as if the succeeding generations were more severely affected. More data needs to be accumulated before we can say anything definitive about this.
Can knowledge about the mutation be used for prenatal diagnosis?
Yes. If a specific mutation has been identified in an affected member of the family, it is possible to determine whether a fetus has the same mutation.
How is prenatal diagnosis done?
Prenatal diagnosis may be done by chorionic villus sampling (CVS) at 10 1/2 -12 weeks of pregnancy, or by amniocentesis between 14 and 18 weeks. You should consult your obstetrician and genetic counselor/medical geneticist to determine which method is best for you.
If the mutation is unknown in my family, is there any other way to have prenatal diagnosis?
Yes. High resolution ultrasound, performed in a center where there is an appropriate specialist, at about 18-20 weeks of pregnany, can be utilized. A sonogram can sometimes identify a small chin and small ears, but diagnostic ultrasound is not a definitive diagnostic technique, and a mildly affected fetus may not be identified.
IMPORTANT: If you are considering prenatal diagnosis for Treacher Collins syndrome, you should consult a genetic counselor or medical geneticist before a pregnancy if at all possible. As discussed previously, looking for the mutation may take a long time. If it is not possible to have testing before the pregnancy, you should contact the genetics professionals as early as possible in the pregnancy.
Will the doctor predict the severity of Treacher Collins syndrome in the fetus?
No. It still will not be possible to predict the severity of the condition. Individuals carrying the same mutation may be affected differently.
What kind of research is being done now?
Now that the gene has been identified, the researchers are trying to learn more about the mutuations in different families and how the mutations can be identified more quickly. They will investigate the function of the gene and how it influences development of the face and ears and whether there are other genetic or other factors that influence the severity of the condition. Knowledge about the function of the gene may lead to treatment or prevention.
You can help yourself/your child and others with Treacher Collins syndrome by participating in research projects. It is easy to do, and you would be fully informed about the project before you agree to participate. Contact the Treacher Collins Foundation to find out how you can do this.
If we are the unaffected parents of a child with Treacher Collins syndrome, should we consider having prenatal diagnosis?
If the mutation in your affected child has been identified, and you want to determine with certainty whether the fetus is affected, you may have prenatal diagnosis. You may choose to do this because of the small possibility of germline mosaicisim as described above.
What kind of surgical correction should I/my child have?
Surgery is like any other specialty: things change all the time, and new techniques are developed all the time. This is not the format to discuss exactly what surgery is appropriate since it has to be tailored to the individual. Surgical correction of the deformities in Treacher Collins syndrome is complex.
The most important thing that you can do is to be sure that you/your child are going to a center, preferably a craniofacial center in your area, that has extensive experience in caring for individuals with Treacher Collins syndrome. A craniofacial team should include professionals such as: plastic surgeons with special training in reconstructive surgery; neurosurgeons; ear, nose and throat specialists (ENT); ophthalmologists; speech pathologists; geneticists; audiologists; orthodontists; social workers; and, a pediatrician with experience caring for children with craniofacial disorders. There are also some physicians and other health professionals with specialized expertise not working in craniofacial centers who can provide you or your child with expert care. The Treacher Collins Foundation has a referral list available of craniofacial centers which provide this team approach with experts in the care of individuals with Treacher Collins syndrome.
When you contact a craniofacial center, asking the following questions may help you decide if you will feel comfortable with the professional care they provide:
1. How many individuals with Treacher Collins syndrome and other craniofacial disorders do they see per year?
2. What is their protocol for caring for patients?
3. Are there other families who have been cared for in their center that you can talk to?
While it may be helpful to engage your local pediatrician to act as your advocate, as a parent or affected individual, you will develop more expertise than anyone. Treacher Collins syndrome is relatively uncommon, and therefore the care of affected individuals is not well known to many physicians.
Do not hesitate to get more than one opinion. A specialist “worth his/her salt” will not object to your getting a second opinion.
How can I afford to have my child go to the “best” doctors?
Many of the craniofacial centers have funds available to help families. Many doctors will waive fees not covered by insurance companies. Some hospitals have special funds for patients with special needs. Ask the contact person at the craniofacial center if there are any funds available. These centers are aware of your financial burden and will help find ways to meet your needs.
What about the psychological aspects of Treacher Collins syndrome?
The psychological issues for people with facial disfigurement and their families are complex. Not only are there potential difficulties for the affected individuals, but for other family members, parents and siblings. Addressing these concerns early and in an open way, sometimes with the help of a counselor or therapist, is essential. It is usual to have some periods that are more difficult than others. Craniofacial centers can refer families to a counselor or therapist experienced in working with the specific needs of each family. The occurrence of genetic problems in a family, and/or the occurrence of facial disfigurement in one or more individuals is upsetting and has wide ranging effects, but most families are able to successfully work through these issues. Individuals with Treacher Collins syndrome can look forward to having a normal family life as adults.
This list of questions and answers is not exhaustive. The most important thing to remember is, despite all of your concerns and unanswered questions, that you have a normal child with Treacher Collins syndrome.
Networking with other families with Treacher Collins syndrome is one of the best ways to keep up with the latest developments in treatment and derive emotional support. It’s a little like having a family that understands.