MDS Study ~ Released 1996

MDS Study ~ Released 2009

Preliminary Research Study Late 2009

MDS Study 1996

This page contains the entire MDS research study done by Dr. Colleen Jackson-Cook, of the Department of Human Genetics, Virginia Commonwealth University, printed in 1996. The study itself is ongoing and information is being collected daily. This study would not have been possible without the contributions of Allison Gregory, M.S. and Lauren Vanner.

If you would like to receive the complete hard copy of this 44-page MDS research study booklet via snail mail, or participate in the ongoing study, please contact Dr. Jackson-Cook . All the information in this study is protected by copyright, 1996, Department of Human Genetics, Medical College of Virginia/Virginia Commonwealth University, first printing May, 1996.

You may also contact Dr. Jackson-Cook or Dr. Len Leshin if you have further questions regarding Mosaic Down Syndrome, the answers of which were not found on this website. 
Introduction

Scientists at the Medical College of Virginia (MCV), Virginia Commonwealth University, have been studying Down syndrome (DS) for over a decade. Recently, we focused on the study of chromosomal events that can lead to Mosaic Down syndrome (Mosaic DS), a less common form of DS. Many family members told us there was a lack of specific resources about Mosaic DS available to them. Several hoped that we could identify resources or help provide them with information.

In response, we have collected information that we hope will be helpful to a wide group of people, including the families of individuals with Mosaic DS, health professionals, educators, and others. With the help of the families involved, we have explored topics such as health, education, and recreation. We have also compared a portion of the information collected with that from a group of individuals who have DS without Mosaicism, to try to determine if there are any significant differences between the groups.

What are Chromosomes?

All people are made from millions of cells, much like a beach is made up of grains of sand. These cells cannot be seen without the help of a microscope, but they are the building blocks of our bodies. Different types of cells make up different parts of our bodies, and have different jobs depending on where they are located. For example, a liver cell has different jobs than a bone cell or a nerve cell.

Inside each cell is a full set of instructions, or blueprints, for how to make a person. Each person has his or her own unique set of instructions, which help determine traits such as height or the color of our eyes. These instructions are located on rod-shaped structures called chromosomes , which are located together in the nucleus, or operating center, of each cell.

Most people have 23 pairs of chromosomes in each cell, or 46 total. The chromosomes are numbered according to their size, with chromosome one being the largest and 21 and 22 the smallest. The 23rd pair is the sex chromosomes, which determine if a person will be male or female. Females have two X chromosomes, while males have one X and one Y chromosome. One member of each pair of chromosomes comes from a person's mother; one's father gives the other pair member. These chromosomes come together at conception, when a sperm and egg meet. Sperm and egg cells have 23 single chromosomes instead of 23 pairs .

Each chromosome contains hundreds of individual instructions, called genes . Genes are made of DNA (deoxyribonucleic acid). One helpful way to think of the concepts introduced so far is as follows. Each gene is like a sentence of instructions. Several hundred genes, or sentences, are lined up to make a chromosome. It takes a full set of chromosomes (23 pairs or 46 total) to complete an instruction manual for how to make a person.

Just as having an extra page of information changes an instruction manual, having an additional chromosome changes the information available to make a person. In the majority of cases of DS, the individual is found to have an extra chromosome 21 in every cell that makes up his or her body. It is the presence of extra chromosome 21 material that leads to the features of DS. This is usually detected through a blood test in which the white blood cells are separated from the blood sample. Special laboratory techniques and a microscope are used to look at the chromosomes from several cells. A picture of the chromosomes from one cell, with each pair lined up in order, is called a karyotype . '

What is Mosaic Down Syndrome?

Because most people with DS have an extra chromosome 21, they will have a total of 47 chromosomes (instead of 46) when a chromosome study is done. This type of DS is called trisomy 21 and is believed to account for about 95% of cases of DS. In the remaining 5% of cases, individuals have either translocation DS or Mosaic DS. In translocation DS, nearly all or part of a chromosome 21 becomes attached to another chromosome in the cell (called a translocation).

About 2-3% of individuals with DS are believed to have Mosaicism . People in medical and scientific fields borrowed this word from the art field. In art, a Mosaic is a decoration made of many small pieces, such as different colored tiles. In people, Mosaicism describes a condition where a person has two or more types of cells that differ in their genetic make-up.

This can be seen by taking a blood sample, as described above, and looking at the chromosomes from several cells. There is one group of cells with the typical number of 46 chromosomes. Then, there is a second group of cells with extra chromosome 21 material. The extra chromosome 21 material can be in the form of trisomy 21 or a translocation, with trisomy 21 being the most common. Very rarely, a person can be made of even more than two types of cells.

When Mosaicism is discovered, it is often described as the percentage of cells having additional chromosome 21 material. For example, a blood test may be done on a baby who has features of DS. Typically, the chromosomes of 20 different cells are analyzed. If it is found that there are 5 cells with the expected number of chromosomes (46) and there are 15 cells with 47 chromosomes, including an extra chromosome 21 (trisomy 21), the baby would be described as having Mosaic DS. In the case, 25% (5/50) of the cells have extra chromosome 21 material. In this example, then, the baby may only be described as having Mosaic DS with a Mosaicism level of 75%.

It has been shown that these percentages may vary between cells located in different parts of an individual's body. For example, the percentage of trisomic cells in a person's muscle cells may be different from that seen in their blood or brain cells. Some of this variation is thought to depend on the point during development at which the Mosaicism first occurs. Sometimes, either through a family doctor or a research protocol, individuals with Mosaic DS will have studies done to look at tissues other than blood. Typically, these include skin or bone marrow. Occasionally, if the individual is already having surgery for another reason, other tissues may be examined. Although the percentages of different cells in the brain may help determine the intellectual capacities of individuals with Mosaic DS, this type of tissue cannot be easily tested.

How Does Mosaicism for Down Syndrome Happen?

There are two main steps, or types of events, that can be involved in leading to Mosaicism in an individual. Both of these are known to happen while new cells are being made from current cells, a process called cell division . There are two general types of cell division. The first type (called mitosis ) allows our bodies to continuously make new cells as we need them. For example, the outer layers, or cells, of our skin slough off as we bathe ourselves or as clothing rubs on our skin. The lost cells are replaced with new ones.

A new cell is made from a current cell, and new chromosomes are made from current chromosomes. To make a new cell, a cell that already exists stores extra amounts of everything it needs. Inside this cell, all 46 chromosomes go through a special process where each one makes a twin, or duplicate copy of itself. Then the cell splits in half, dividing its contents equally to make two new cells. It is very important that each chromosome separates from its twin, so that there are 46 chromosomes in each new cell. Sometimes a chromosome does not separate from its twin, and both copies go into the same cell. This is called nondisjunction because the two copies fail to disjoin. Nondisjunction leads to cells with extra or missing chromosomes.

The second type of cell division (called meiosis) is used only to make sperm or egg cells. Sperm and egg cells are made from cells that have 23 pairs of chromosomes. These cells split, in a different way from mitosis, so that two new cells with only 23 chromosomes are made. Nondisjunction can occur in this process, too, causing sperm and egg cells to have extra or missing chromosomes.

One way that Mosaicism arises is through a nondisjunctional event during mitosis. This occurs after conception. During conception, a sperm and an egg cell, each with 23 chromosomes, come together, completing fertilization. Later, after several cells have been made, one cell has difficulty splitting its chromosomes evenly. The result can be one cell with 47 chromosomes and three chromosomes 21. This cell continues to make new identical cells, through mitosis, and each new cell will also have an extra chromosome 21. You may wonder if there is another cell that is missing a chromosome 21? Yes, when nondisjunction happens, this type of cell is also made. However, it is harder for the cell to live with a missing chromosome than an extra one, and this type of cell usually doesn't survive or replicate.

The second sequences of events that can lead to Mosaicism involves nondisjunction occurring twice. The first nondisjunctional event occurs when a sperm or egg cell is made. The sperm or egg cell has 24 chromosomes, with an extra chromosome 21. If the story ended here, this would lead to a baby with trisomy 21, without Mosaicism. However, in cases with Mosaicism another nondisjunctional event happens after conception. As the cells of the embryo begin to make copies of themselves, the extra chromosome 21 is lost from one of the cells, and a new cell is made with 46 chromosomes, instead of 47. As each of these cells continues to double, it leads to a baby with two different types of cells, or Mosaicism.

By looking at DNA information along the chromosomes, we and other researchers have learned that the explanation involving two nondisjunctional events, one before and one after conception, is the most frequent way for Mosaicism to happen, accounting for about 70% of cases. The other 30% usually occur by a single chromosome separation problem in the embryo. Studies are currently underway to learn if there are any differences in the development or health of cases with Mosaicism arising by different mechanisms.

Because translocation DS is relatively rare, and Mosaicism for translocation DS is seen even less often, it is hard to explore how translocation Mosaic DS occurs. It is likely that similar sequences of steps also lead to this condition, meaning that there may be a single change after conception, or changes both before and after conception.

A re there differences between Mosaic Down Syndrome and Down Syndrome?

A syndrome is a collection of characteristics or symptoms that have a common cause. People with DS and Mosaic DS share many characteristics, due to extra chromosome 21 material in all, or a portion of, their bodies' cells. Each individual with DS or Mosaic DS will not have all the features seen in these syndromes, but will have a unique combination. Some of the common features are mild to moderate mental retardation, heart problems, problems with the digestive tract, increased colds or respiratory infections, and a characteristic facial appearance.

As with any group of people, much variability is seen in the features of individuals with Mosaic DS. Some people with Mosaic DS have similar or more serious health problems or developmental delay when compared with people having DS. Others have less developmental delay and relatively few health problems or characteristics of DS. On average (not all cases), individuals with Mosaic DS seem to have many features of DS, but often more mild presentations, probably due to the portion of their cells that lack the extra chromosome 21.

There are several reasons why people with Mosaic DS show a wide range of physical and developmental findings. Explanations include differences in (1) the percentage of trisomic cells in various tissues (blood, brain, heart, etc.); (2) the sequence of events leading to the Mosaicism; and (3) the DNA information (from one or both parents) on the chromosomes 21 in the two types of cells. Also, although Mosaic DS is caused by a portion of cells having an extra chromosome 21, it is important to remember that there are 22 other pairs of chromosomes in the person with Mosaic DS. Certainly, differences in the information found on these chromosomes adds to the variation seen among people with Mosaic DS, as it does for all individuals.

Some investigators have tried to determine if there is a relationship, or correlation, between the percentages of Mosaicism people have in their blood and their intelligence quotients (IQ). In this type of study, certain statistical tests are used to decide if the relationship they find is real, or statistically significant. Although some investigators have noted a trend toward an increased IQ with smaller percentages of trisomic cells, a clear relationship has not been consistently demonstrated. This may be due, in part, to the small numbers of people with Mosaic DS who were studied (about 30).

Beyond IQ, there are many other questions that can be asked about Mosaic DS. For example, "Is a baby born with Mosaic DS just as likely to have a heart defect as a newborn with DS?" Or, "Does Mosaicism affect when a child will first walk or talk?" These are some of the difficult questions we have asked in our study.

About our Group (the participants).. .

Since Mosaicism is seen in a small number of people with DS (2-3%), we needed help to identify families to be in our study. With the aid of the National Down Syndrome Congress (NDSC) the Down Syndrome Support Group of Greater Richmond, Inc., and other parent groups, we had the opportunity to announce our study in local and national DS newsletters. We were also able to contact families while attending the NDSC's annual conference in Washington D.C. (held in August, 1995).

The group described in this booklet included 45 individuals with Mosaic DS, ranging in age from four months to 33 years. The level of Mosaicism noted (usually from diagnostic chromosome reports) ranged from 16% to 97%. There were 24 males and 21 females, from 26 U.S. states and territories, including Alaska, Colorado, New York, Washington, Texas, Iowa, Virginia, Missouri, Vermont and Puerto Rico. The majority of the group was Caucasian (90%), but African American and Hispanic families also participated. Information about individuals with Mosaic DS and their families was collected by sending a questionnaire to each family. In most cases, the mother or father of the individual with Mosaic DS completed the questionnaire and returned it to us.

We collected two general types of information about Mosaic DS. First, we collected descriptive information, which helped us create a very general picture of what it's like to have Mosaic DS. An example of the type of question asked in this case is, "What activities does your family most enjoy doing together?" Parents had several lines to answer these questions in their own words.

The second kind of information we collected was more specific, usually answered either by circling yes or no, or giving a number, such as an age. Examples are, "At what age did your child first crawl?" or "Was your child born with a heart defect?" We used this information to learn more about people with Mosaic DS. We also compared the people with Mosaic DS with a person having non-Mosaic DS of the same sex and approximately the same age. Then, we compared the two groups using statistical tests.

Development

One area we explored is how individuals with Mosaic DS develop and what types of special help they may need. We learned about early development by asking parents when their children reached certain milestones, such as walking or talking. A summary of these results is presented in Table 2 (below). A statistical test, called a paired t-test, was used to determine if there were real, or statistically significant, differences between the development of individuals with Mosaic DS in comparison to their brothers and sisters (siblings). The results suggest that most individuals with Mosaic DS develop at a delayed pace in comparison to their siblings without Mosaic DS. This was shown for each milestone included in the table, with the exception of when the child first rolled over.

Physical, Occupational, and Speech Therapy Participation

Families reported that many children and adults with Mosaic DS received special help in developing skills, such as language or coordinated movements. They commonly participated in physical therapy (PT), occupational therapy (OT), and speech therapy.

About 70% of the group had participated in PT. Of those who had not, about half were either very young or were old enough that this service may not have been available to them as children. Many parents reported using PT to help their children improve their low muscle tone, a finding that is common in DS. They also practiced the development and coordination of large muscle movements (gross motor). Some specific goals parents mentioned were walking, stair-stepping, and being aware of body location in space. Some parents mentioned that they started PT from birth to prevent the development of bad habits and help their children get a head start in possible problem areas. Most of the group with Mosaic DS began PT between birth and six months of age, and ended it by about three years, although some continued longer (often until their child learned to walk). The amount of time spent in PT varied from once per month to twice weekly. People received PT in various places, including at home, daycare, school, and early intervention programs.

About 73% of the group received OT. Again, about 1/3 of those who did not were either very young or older members of the group. In OT, children and adults with Mosaic DS focused on gaining independence through developing skills that require more fine or delicate muscle control. Some of the goals parents mentioned for OT included learning to hold a bottle or cup, writing, tying shoes, and dressing.

Parents reported that their children usually started OT at an older age than PT, although a few started as early as one month. Their OT sessions also continued for a longer period of time, with several children still receiving OT while in grade school and high school. In addition, one older woman with Mosaic DS had OT incorporated into her work training program. Thus, OT may be helpful for people throughout their lives. As with PT, the amount and location where OT was received varied.

Most individuals (about 85%) with Mosaic DS in this study received speech therapy. Most of those who had not were very young, but planned to start soon. Some parents had their children start speech therapy early, realizing they may need extra help. Others waited to start therapy until their children showed delay in developing speech skills or had problems making certain sounds. Some of the older individuals continued to have therapy into their high school years and beyond.

Parents mentioned several findings of Mosaic DS that they felt made speech development especially difficult. These included low muscle tone, problems with tongue thrusting, and ear infections or fluid in the ears that can affect hearing. Several parents also noted that if their children spoke slower, their speech improved. A few families shared that their children used inflection and body language very well to make their points.

Some children had specific challenges that they worked on in therapy, such as a stutter. Others worked on more general skills, such as making clear sounds (enunciation) and putting sounds and words together (articulation). Some focused on other forms of communication as well. One child learned to use a communication board. About 2/3 of the group were taught sign language, usually during the same period of time that they were learning to speak. Many parents believed that learning sign helped their children develop verbal skills. Several children would say a word and sign it at the same time. Others used specific signs, such as names of food, to express needs until they were able to put together more complex sentences. None of the individuals continued using sign as their primary language. Instead, as verbal skills improved, the use of sign decreased.

Physical Characteristics and Health

People with DS and Mosaic DS share many findings in common. For this reason, it may be noticed that they resemble members of their families, but also resemble each other. We asked parents to describe a number of traits in their children that are common in DS (table below). It is important to remember that some of the physical characteristics described may change with age, such as hearing loss. This table illustrates findings for our particular group of 45 individuals, with a wide range of ages.

A congenital condition is one that is present at birth. Some congenital conditions seen in the group included heart defects and gastrointestinal changes. Nearly 1/3 (13/45) of families reported that their child had some sort of gastrointestinal or digestive problems. Most of these were fairly common, including constipation, excessive gas (flatulence), and indigestion. Four were born with more serious congenital problems that usually require surgery or special medical treatment. These included changes in the structure of the pancreas (annular pancreas) and bowel (malrotated bowel), duodenal atresia (narrowing of the intestine), an umbilical hernia, and imperforate (sealed) anus.

Forty-four percent (20/45) of families reported that their child was born with a heart problem, such as a change in the heart's structure or a murmur. Six children required corrective surgery. The remaining changes were treated with drugs, "fixed themselves" over time, or did not require treatment, such as murmurs.

The most common changes involved some sort of opening in one or more of the inner walls of the heart that divide it into four chambers. This type of change is often described as a "hole in the heart" and includes conditions called AV (atrioventricular) canal (four cases), VSD (ventricular septal defect) (one case), ASD (atrial septal defect) (7 cases), and endocardial cushion defects (one case). There was one case of tetralogy of Fallot, which involves four specific changes in the heart, and five cases of PDA (patent ductus arteriosus), where a vessel that usually closes after birth remains open. Pulmonic stenosis (a narrowing of the pulmonary artery) was seen in two individuals, a change in the mitral valve was observed in one, and two had murmurs for which no additional information was available to explain the cause. Some children were born with more than one change in the heart. For example, two were born with septal changes, like a VSD, and a PDA.

People with Mosaic DS are involved in many sports

Many parents mentioned findings they noticed in their children that we did not specifically ask about. Some of the more common characteristics included small ears that are low set, a noticeable space between the first and second toes, Brushfield spots (white flecks on the colored part of the eye), strabismus (eyes appear crossed), and the late eruption of baby teeth and adult teeth. Other findings that were reported included cleft lip and palate, umbilical hernia, and tracheal malacia (narrowing of the windpipe).

Three families reported that their children were being treated with Ritalin for attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD). A few were being followed for atlantoaxial instability, a condition seen in DS where the neck is somewhat unstable. A few children had different degrees of hearing loss. One member of the group was successfully treated as a young girl for acute lymphocytic leukemia (ALL).

Participation in organizations and clubs

When asked about thyroid testing, several parents reported that their children had not been tested or that they did not know if they had been tested. Given that thyroid problems are detected more often in people with DS than in the general population, it is recommended that individuals with non-Mosaic DS be screened yearly. This is particularly important, since thyroid problems can be treated. Three individuals in this group were reported to have hypothyroidism. This suggests that children having Mosaic DS also have an increased risk for thyroid problems and should also consider having annual testing.

When asked about their children's health, there were a few conditions that a great number of families mentioned. Most of these were related to the respiratory tract or ears. The most commonly mentioned health problems were recurrent ear infections (or fluid in the middle ears) and common colds or upper respiratory tract infections (URI's). Respiratory infections affected the nasal passages, throat, and lungs. Also mentioned were asthma, allergies, bronchitis, pneumonia, sinus infections, and blocked tear ducts.

Many children and adults with Mosaic DS had surgeries for the health conditions that they were either born with or acquired. About 56% (25/45) had one or more surgeries (tubes to drain middle ear, corrective eye wear or other surgeries, not including placement of tubes in ears). The most common procedure was the placement of tubes in the ears to drain fluid (myringotomy). Tonsillectomies and procedures to open blocked tears ducts (lacrimal ducts) were also common. A few individuals had surgery to correct strabismus, a condition where both eyes do not move together and appear crossed.

Another health-related issue in DS is excessive weight gain, which is reported to occur in about 25% of individuals with full DS. This usually occurs around the time of puberty. Excessive weight gain (starting between ages six and 27) was reported for five cases. Given the relatively young ages of members of the group, additional individuals may experience weight gain later in life. Several families noted that they tried to establish good eating and exercise patterns to prevent gain. In describing strategies to control weight, common themes were education and supervision. Specifically, parents described teaching their children to reduce fats and eat healthy foods, supervising food access, limiting snacks, and encouraging exercise.

Learning and Education

Almost all (43/45) of the individuals with Mosaic DS started their formal learning processes in early intervention programs. One of those who did not was in the older range and early intervention had not been available when she was an infant or toddler. In early intervention, adults and babies interact in a specialized way meant to enhance the infant's development and help him/her learn new skills. Of those having early intervention, the majority used public programs, while the remainder used private ones. Public programs were usually run by the county or state. Some programs were provided through agencies like the United Way or through state universities.

Parents reported that most intervention programs provided OT, PT, and speech therapy. Often, group play or play therapy was also a component. Some also included parent support groups, social work services, case management, or special help in obtaining services or assistive devices from other agencies. Programs were offered in a wide variety of settings, including center-based, home-based, and combination programs.

Much like early intervention, of those who were school age or older (30 individuals), the majority attended public school programs. Programs varied between individuals and addressed special needs in different ways. Some were involved fully in special education programs. One child was in a regular elementary classroom with no special help. The majority, however, fell somewhere between these two ends of the spectrum, with combination programs. Many were included with their peers for certain subjects, such as social studies or art, and went to a resource room for other subjects, such as reading or math. Many families also described that their children's education programs had adjusted over time. For example, a child may have started in a special education classroom, then progressed to situations with increasing inclusion.

Eighteen of the 30 children school-age or older had been involved in inclusion programs at some point during their educations (primarily through public school). Ten families reported that their children had been involved in full inclusion with varying levels of support. States in which inclusion appeared to be available to these families included Georgia, Illinois, Louisiana, Maryland, Massachusetts, Michigan, Montana, New Jersey, New York, North Carolina, Ohio, Puerto Rico, South Carolina and Virginia.

Comparisons of Mosaic and non-Mosaic DS

One way to explore what differences may exist between conditions like Mosaic and non-Mosaic DS is to identify a group of individuals with each condition who are otherwise very similar. The more similar the two groups are in other ways, the easier it becomes to decide what differences may be due to the Mosaicism. As you may imagine, putting together these groups can be difficult. We were able to match 28 of the 45 individuals with Mosaicism in this study by sex and age with individuals having full DS, creating two groups. Once the 28 pairs were matched, we also found that the family incomes and education levels of the parents were similar between the two groups.

We then compared the two groups for three major categories. First, we wanted to compare how parents rated their children for having certain traits, such as low muscle tone or hearing loss. Secondly, we wanted to compare when children in the groups reached milestones of development. Finally, we wanted to compare services the two groups were receiving.

We did not find statistically significant differences in how parents described traits of their children with Mosaic or non-Mosaic DS. This was somewhat surprising because many parents we have spoken with described their children with Mosaicism as appearing "mild" or having few features of DS. There are several reasons why real differences may be difficult to identify. First, it is difficult to detect differences between small groups. Second, several of the traits we asked parents about may be challenging to answer with "yes" or "no." For example, although two children may both have low muscle tone, one child's low tone may be much more severe than the other's. We are continuing these studies with physician evaluations of some of these traits. It is hoped that the additional studies will provide further insight about this question.

We found a more meaningful trend when we looked at development in the two groups, as reported by parents. With the exception of speech, there was a trend toward individuals with Mosaic DS reaching the milestone evaluated at an earlier age. However, a clear difference (identified by statistical testing) was apparent only for crawling and walking. The trend that we see suggests that further research needs to be done to examine possible differences.

Finally, we found no significant differences between the two groups when parents were asked about services they used. Services that we asked about included PT, OT, speech therapy, early intervention, sign language training, school programs, vocational training, camps, and respite care. This suggests that although it is still unclear if differences exist between Mosaic and non-Mosaic DS, families and individuals with Mosaicism have resources available that are similar to those for full DS and appear to be using them.

In speaking with families, we found that one of the greatest frustrations they described was not knowing what Mosaicism means for their children or what to expect. Through our study we have begun to address these questions, and our results have helped give us and other investigators direction for further study. Also, we are currently exploring how the percentages of Mosaicism in individuals may influence their rates of development. Preliminary studies suggest that a relationship between these variables may exist, but further investigation is needed to obtain a clearer understanding.

Recreation and Family Life

We learned that people with Mosaic DS keep busy! Members of our group were involved in a number of sports, groups, and organizations, and also enjoy spending time with their families.

Sixteen members of the group had attended some type of summer or day camp. A variety of camps were described, including public camps, camps for children with special needs, religious camps, and even a specialized "speech camp." One woman with Mosaic DS, currently in her thirties, enjoyed her camp experience so much that she now goes back and serves as a volunteer assistant counselor.

Young Adults with Mosaic Down Sydrome

There were three men and one woman in our study group over the age of 18. Their parents described the levels of independence they developed as young adults and their involvements in the community.

All four of the young adults were described as having achieved helpful living skills, such as telling time and doing basic reading, writing, and math (adding and subtracting). It is important to note that each individual's skills varied within these categories. Two of the group used public transportation, such as the bus or train. One started to do so at age 16 and the other at 19. Each individual had his/her own experiences in working and volunteering in the community.

One young man, age 29, began working when he was 19. He worked four years as a courtesy clerk in a grocery store, and his responsibilities included bagging groceries and collecting carts. At age 27, he stopped working for a salary, but started a volunteer program. He currently volunteers in a local hospital laundry facility, stacking and folding garments. In his free time he enjoys being part of a local acting group and performs plays and musicals.

In the cold winter climate of his home, a second young man's household chores include both shoveling snow and using the snow blower. At age 18, he became employed at K-Mart. His duties include putting tags on apparel, bagging items, and greeting customers as they enter the store.

The third young man, age 24, began working at 14 years of age. His most recent work involves folding boxes for medical sharp waste and dismantling pallets in a warehouse. At age 19, he moved into a group home that is only a 20-minute car ride from his family. His parents report that he "loves his job" and works about 40 hours weekly. He often spends his weekends at home and enjoys taking short trips with his parents to visit relatives and friends.

Finally, a young woman, currently age 32, graduated from high school with a modified diploma in 1982. She received work-training in several settings, including school and a program at a local university, and has held several jobs, including employment at a preschool and restaurant. Participating in the Special Olympics and following television and movie stars are included in her hobbies.

Resources

This informational booklet was created in response to a large number of families describing a lack of available resources specifically discussing Mosaic DS. Several parents commented that there are many excellent resources about DS in general, but few of them contain more than a sentence or two about Mosaicism. We asked families to identify the resources that they have used most often to learn about Mosaicism and DS in general.

We also asked them to rank the top three sources of information that they used (with number one being the most used and three the least) from the following choices:

* pediatrician 
* medical geneticist 
* other medical doctor 
* genetic counselor 
* other health professional 
* social worker 
* national support group/DS organization 
* local support group/DS organization 
* medical books/ journals/ resources 
* other books/ journals/ resources 
* other

As a group, families ranked their pediatricians, national support groups or DS organizations, and other books/journals/resources as the three resources most often used. Several parents chose "other" as one of their choices and offered suggestions of additional resources. These included teachers, therapists, daycare providers, the Internet, DS clinics, and perhaps most importantly, other parents of children with DS.

What is the chance of having another child with mosaic down syndrome? 
Is testing available?

After having a child with any genetic condition or health problem, some families are interested in exploring the chance of having another child with the same condition. The chance typically given for having another child with DS is about I%, or a I in 100 chance.

In families in whom a child with DS (without Mosaicism) was born, it is expected that almost all of the cases were due to an extra chromosome 21 in the sperm or egg. This suggests that for the portion of cases of Mosaic DS where the first change occurred in the sperm or egg, the recurrence estimate of about 1% should also apply. It is not clear if this is the best estimate for families in whom Mosaic DS occurred after conception. Although about 1% is currently the best estimate, their chance may be lower than this.

During future pregnancies, some families may wish to learn in advance if the developing baby will have a type of DS. There are several testing options for families in this situation. Some of these tests are diagnostic tests (directly look at the baby's chromosomes). Others are called screening tests. These tests help predict the chance that the baby may have a problem. There are two types of diagnostic tests that can be done during pregnancy to look at the baby's chromosomes: (1) chorionic villus sampling, or CVS, and (2) amniocentesis.

In both CVS and amniocentesis, doctors are careful to use clean, sterile procedures and to check the baby while the test is being done. Both tests are typically done with ultrasound guidance. This means that while the test is being done, ultrasound is used to show an image of where the baby is and how it is responding to the test. However, there is still a risk of miscarriage for both CVS and amniocentesis. This risk is typically quoted as about 1% (1/100) for CVS and 1/2% (1/200) for amniocentesis. The two tests are also done at different times during pregnancy. CVS is usually done around the tenth week of pregnancy, while amniocentesis is usually done later, typically during weeks 14-18 of pregnancy. As you may imagine, deciding to have this type of prenatal testing is a personal choice for each family. This decision can be especially difficult due to the chance of miscarriage associated with these procedures. There are other screening tests that are less accurate, but do not have significant risks associated with them.

One of these screening tests is done by looking at certain proteins in a pregnant woman's blood (maternal serum screening). Depending on how many proteins are checked, this can be called an MSAFP (maternal serum alpha fetoprotein) test, a double screen, or a triple screen. The test is done early in the second trimester of pregnancy. Based on the levels of different proteins, the mother's age, and additional factors (such as the week of pregnancy), the chance of having a baby with DS or another chromosome problem is estimated. If this chance is greater than or about equal to the risk of amniocentesis, the pregnant woman will be offered this procedure. The risk associated with the screening test is only that of having blood drawn (which can rarely lead to effects such as infection). However, the maternal serum test is not a diagnostic test and does not directly evaluate the baby's chromosomes.

A second type of test that has no known risk is a detailed ultrasound, sometimes called a fetal scan. This type of ultrasound is typically done around week 20 of pregnancy. In this type of ultrasound, the baby's organs, such as the heart, kidneys, and brain, are examined closely. Ultrasound can find many changes in structure, such as some heart defects. However, it cannot tell whether a birth defect is caused by a chromosomal change. Also, it is possible for no changes to be found on ultrasound and for the baby to still have a chromosomal condition. If a change is found through ultrasound, some families may then decide to have an amniocentesis.

If you are considering pregnancy or are pregnant, you can ask your doctor for more information about these testing options. Most women have the opportunity to discuss the details of testing with a genetic counselor, nurse, or doctor before the test is done. In addition, follow-up counseling and support is available to families who are found to have an increased chance for having a baby with a problem or who are given the diagnosis of a chromosomal condition in the developing baby.

Parents' Thoughts on Mosaicism

We asked the parents in our study what they felt were the most important things to tell new parents of children with Mosaic DS. Here are some of their responses.

"These kids are very loving and easy going children. They have been developmentally delayed, but are ever so willing to learn and can progress along very well."

"He or she will just be a little slower to catch on in a lot of areas. He or she will bring a lot of joy and fun to your life that a lot of people will not experience."

"The world seems pretty bleak when you first learn the diagnosis, but it isn't nearly as bad as it seems at that moment...As time goes on, you'll understand that 'Life Goes On' just as if the child is 'normal' with a few extra corners to go around."

"I can't honestly say that her having Mosaic Down Syndrome is apparent at all. I would say what I would say about DS period: Your child will give you more happiness than you can imagine right now. I have learned so much from my children with DS."

"Be consistent, keep your expectations the same as with any other child."

"There is a wide range of how a child may be affected. Be optimistic and hope for the best."

"Our kids are children first--treat them as you would any other child until something occurs that you need to treat or deal with differently. Expose them to everything, give them a chance to succeed or fail."

"New parents should be put in touch with other parents who have Mosaic Down Syndrome children."

"For the first few years I focused on the Mosaic part. The reality is that he's not different. There are kids with trisomy 21 who are brighter and kids with Mosaicism that do very poorly."

The most important thing can't really be told or understood, and that's to worry less and enjoy the baby more."

"We think early intervention is so important."

"Pursue educational opportunities--have a sense of humor and learn not to care what people think."

"They should feel encouraged by the Mosaicism, but their child still has Down Syndrome and they should not deny their child of special services that will meet their special needs."

"Do everything for your baby you can, including therapy. It is so rewarding when my daughter accomplishes something we've worked so hard on."

"Do everything possible to help your child and wait and see if Mosaic means anything. Play it down if you are trying to get SSI."

"We were told shortly after our daughter was born that there was little difference between Mosaic DS and trisomy 21. It has been our experience that there is a great difference..."

"It took us a while to accept that no one could tell us whether the Mosaicism makes a difference."

Acknowledgements

This project would not have been possible without the consistent help and commitment of the families involved. We acknowledge them and thank them for their many contributions. One parent in particular, Peggy Vaughn, has actively collaborated with us in order to expand and strengthen a parent group that she started during our study. We thank her for her efforts. (Please note that at the time this research study was published, Peggy Vaughn WAS the contact person for the Mosaic DS parent group. I have since taken over for her as MDS List Facilitator, and can be reached by e-mail .)

We also thank Dru Barbee and the NDSC, the Down Syndrome Support Group of Greater Richmond, Inc., PODS of Northern Virginia, and other parent groups in Virginia for their help and support and for allowing us to announce the study in their newsletters.

Lastly, in order to make the valuable information that we collected available to others, we applied for and received grant support from the R. Clifton Brooks Medical Fund and the Children's Miracle Network of Richmond, VA.

Glossary

Amniocentesis A procedure used in prenatal diagnosis to obtain amniotic fluid containing cells from the developing baby for analysis.

Cell Cells are the building blocks that make up most of the tissues of the body. Examples are red blood cells or liver cells.

Cell division The process in which new cells are made by the division of one current cell into two identical cells.

Chorionic villus sampling (CVS) A procedure used in prenatal diagnosis to obtain cells (chorionic villi) that are fetal in origin from the placenta for analysis.

Chromosomes The rod-shaped structures (found in most cells) that contain genetic information, or blueprints. In humans, each cell typically has 46 chromosomes, or 23 pairs.

Genes Instructions, or blueprints, for growth and development. Genes help determine our features, such as eye color or height.

Karyotype A picture of the chromosomes from one cell, with pairs lined up in order according to size.

Maternal serum screening A procedure in which the levels of one or more proteins in a pregnant woman's blood are analyzed to help predict the chance that the developing baby has certain chromosome conditions or birth defects.

Meiosis The type of cell division that leads to the production of sperm and egg cells.

Mitosis The type of cell division that leads to the production of most of the cells of the body.

Mosaic Down syndrome A form of Down syndrome (seen in about 3% of cases) in which a person typically has 2 types of cells, one with 46 chromosomes and the other with 47, including an additional chromosome 21 (typical trisomy 21).

Mosaicism A condition in which an individual has two or more types of cells that differ in a portion of their genetic make-up.

Nondisjunction A condition where a chromosome does not separate properly, leading to an extra or missing chromosome in cells.

Translocation Down syndrome A type of Down syndrome (seen in about 4% of cases) that occurs when part of a chromosome 21 attaches to another chromosome. For these cases, there will be three doses of genetic information for part of the chromosome 21.

Trisomy 21 In each cell of the body there is an extra chromosome 21, with a total of 47 chromosomes. About 95% of individuals with Down syndrome have trisomy 21.

Ultrasound A procedure in which high frequency sound waves are used to visualize structures inside the body. For example, ultrasound is used to visualize structures of the developing baby in the uterus.

Colleen Jackson-Cook,PhD 
Department of Human Genetics 
Virginia Commonwealth University 
P.O. Box 980033 
Richmond, VA 23298-0033

Phone: (804) 828-9632 begin_of_the_skype_highlighting              (804) 828-9632      end_of_the_skype_highlighting begin_of_the_skype_highlighting              (804) 828-9632      end_of_the_skype_highlighting ext. 118 
Fax: (804) 828-3760 
E-mail address: JACKSONC@HSC.VCU.EDU

You may also contact Lauren Vanner, at this same address.