skullcrushed's blog: "22q11"

DO NOT JUST RATE AND MOVE ON PLEASE READ ALL What is 22q11.2 Deletion Syndrome? The 22q11.2 Deletion Syndrome is an abnormality on the twenty-second chromosome that can cause such health problems as heart defects, immune deficiency, cleft palate, developmental delays, learning disabilities and social/emotional issues. Present in one out of every 2,000-4,000 live births, in 1 in 68 children with congenital heart disease, and in five to eight percent of children born with cleft palate, 22q is almost as common as Down syndrome, a widely recognized chromosomal disorder. What Causes the 22q11.2 Deletion Syndrome? 22q is a “new deletion” (loss of chromosomal material) that may or may not run in the family. In fact, only about 10 percent of the time does a parent have the deletion as well. So, if it isn’t hereditary what causes it? According to geneticists, the root of the disorder lies within a person’s genetic makeup. You see, most people have 23 pairs of chromosomes (46 total), with one of each pair coming from the mother and the other from the father. Numbered one through 22 (the 23rd pair determines the sex of the baby), chromosomes are divided into two parts called the arms. The top part is the “p” arm and the bottom is the “q” arm. People with a 22q deletion have a small part of the “q” arm missing. When the deletion is not present in a parent, it is new (de novo) in the child. It is nothing that the parents did or didn’t do to make it happen. It just happens. What are the Signs and Symptoms of 22q11.2 Deletion Syndrome? While the health effects of 22q vary from patient to patient, the common medical conditions include: • Cardiovascular Defects • Feeding Difficulties • Gastrointestinal Problems • Immune System Problems • Growth Problems • Palatal Anomalies • Kidney Differences • Hearing • Low Calcium • Autoimmune Disease • Spine Differences • Cognitive and Speech Delay • Behavioral Differences (e.g.ADHD and Autism) What Are the Treatments for 22q11.2 Deletion Syndrome? While there is no “cure” for 22q, there are ways to manage its problems. And the earlier these symptoms are detected, the more doctors can do to help. That’s why, when diagnosed with this condition, evaluation is recommended in the following areas: • Audiology • Cardiology • Child development and psychology • Cleft palate • Ear, nose and throat • Endocrinology • Feeding/nutrition • Genetics • Immunology • Neurology • Orthopaedics • Urology Cassie and Brooke from the U.S. Jared from the U.S. Cardiology Even if a child doesn't have a known heart defect, a cardiologist's evaluation is important, although the likelihood of the cardiologist's finding a previously unrecognized problem is low. An evaluation usually includes a chest X-ray, an electrocardiogram and an echocardiogram. Child development and psychology Children with a 22q11.2 deletion may have learning style differences requiring some extra help in school. In addition, young children may have delays in their developmental milestones and might benefit from early intervention, such as physical, occupational and speech therapy. That's why it's important to take your child for developmental testing on a regular basis to determine if he's having any problems and to identify appropriate intervention, when needed. Cleft palate Your child should see a plastic surgeon who specializes in cleft palate and velopharyngeal incompetence. In addition, she should see a speech and language pathologist who can also assess speech, language and -- if she's young -- feeding. Some centers have specialized computer methods of objectively measuring speech to decide if intervention is necessary. Some teams also have growth specialists and dentists who monitor face, jaw and tooth growth. Ear, nose and throat and audiology This evaluation may be part of the cleft palate team evaluation. Children with a cleft palate often have trouble with ear infections and can benefit from seeing an ear, nose and throat (ENT) doctor -- also called an otolaryngologist. In addition, an ENT can help children who have problems with " breathing="breathing" as="as" a="a" result="result" of="of" their="their" since="since" some="some" children="children" with="with" deletion="deletion" may="may" also="also" have="have" hearing="hearing" your="your" child="child" benefit="benefit" from="from" test="test" endocrinology="endocrinology" some="some" chromosome="chromosome" problems="problems" low="low" calcium="calcium" when="when" newborns="newborns" and="and" need="need" during="during" this="this" the="the" cardiologist="cardiologist" or="or" pediatrician="pediatrician" will="will" handle="handle" if="if" problem="problem" to="to" see="see" an="an" endocrinologist="endocrinologist" in="in" older="older" growth="growth" short="short" require="require" hormone="hormone" an="an" can="can" feeding="feeding">nutrition Children with a 22q11.2 deletion often have feeding difficulties, especially when they're newborns. A pediatrician who specializes in feeding can help. Your child's healthcare provider will only recommend an evaluation if a problem already exists. Genetics The geneticist is the person who's most likely to have an overview of your child's diagnosis. The geneticist stays up-to-date with the latest research about the 22q11.2 deletion. That's why it's important to take your child for a yearly evaluation, so the geneticist can answer your questions about his general care, as well as the chances that the disorder will recur in any other children you may have. Immunology Many newborns with a 22q11.2 deletion have problems with their immune systems, so they may have trouble with infections or certain vaccines. Most children outgrow this problem by their first birthdays, but some of them continue to have trouble into later childhood and adulthood. In addition, some children develop autoimmune diseases related to their immune deficiency, such as juvenile rheumatoid arthritis, ideopathic thrombocytopenia, vitiligo and Graves disease. Your child should be evaluated by an immunologist at least once. Neurology Some children with a 22q11.2 deletion have a seizure disorder (unrelated to low calcium) or balance problems -- which require a neurologist's services. Ask your child's healthcare team if an initial evaluation with a neurologist may be helpful. Urology Some children have kidney problems -- even a missing kidney -- which a renal (kidney) ultrasound would detect. In addition, some children have urinary tract infections, urinary reflux, bedwetting or urinary frequency. If your child is having these types of problems, he should see a urologist who is a specialist in the chromosome 22q11.2 deletion. Other The problems children with a 22q11.2 deletion have may vary widely, but some other problems include: • constipation • leg pain • differences in the blood vessels in the neck that lead to the brain (carotid arteries) Other, less common, problems include: • bony abnormalities -- such as extra fingers, extra ribs, a missing forearm bone and spine problems that sometime leads to spine curvature (scoliosis) • spina bifida • juvenile rheumatoid arthritis or other autoimmune disorders, such as ideopathic thrombocytopenia, vitiligo and Graves disease • eye problems, such as colobomas • premature fusion of the "soft spots" (fontanels) -- called craniosynstosis • emotional or psychological problems • intestinal malrotation • diaphragmatic hernia • Hirschsprung's disease • tracheoesophageal fistula • laryngeal web • imperforate anus • absent uterus If your child has problems in any of these areas, she'll be referred to the specialists who can care for them. Frequently Asked Questions About the Chromosome 22q11.2 Deletion What is a genetic disorder, and how does a genetic disorder cause health and learning problems? A genetic disorder is one that involves a difference in a chromosome or a single gene. Chromosomes are small structures found in every cell in the body. In human beings, each cell has 23 pairs of chromosomes. Each pair consists of one chromosome from the mother, carried in the ovum or egg, and one chromosome from the father, carried in the sperm that fertilized the egg. The chromosomes carry even smaller structures called genes. Genes contain the information that determines all of an individual's characteristics -- everything from height and eye color to predisposition to chronic illness. Occasionally, a baby is conceived with extra or missing chromosomal and genetic material. Since the chromosomes and the genes they contain orchestrate the body's growth and development, a range of physical and behavioral problems may result. In the case of a chromosome 22q11.2 deletion, genetic material is missing (or deleted) from chromosome pair number 22. The "q" in the name of the disorder refers to the precise location of this missing material -- on the q arm (long arm) of the chromosome. Chromosomes are so small that they can only be examined under the microscope. Genes are even smaller, requiring sophisticated molecular testing. Does the chromosome 22q11.2 deletion run in families? Most cases occur at random and aren't inherited or related to any identifiable cause. However, approximately 5 to 10 percent of children with a chromosome 22q11.2 deletion inherit it from a parent who has a mild, usually undiagnosed, form. Because the disorder is so variable, even people from the same family, with the same deletion, may have very different kinds of problems. When one parent has a chromosome 22q11.2 deletion, the chance of passing this disorder on to a child is one in two, or 50 percent, with each pregnancy. More Information 1. What is a chromosomal deletion? Before discussing chromosomes and genes it’s helpful to back up and talk about cells. All living things are made up of cells. All humans are made up of cells. Chromosomes are located within the nucleus of the cell. Chromosomes are visible under the microscope. They are subsequently identified and lined up – forming a karyotype. Within a karyotype the chromosomes are: • arranged in pairs – totaling 46 chromosomes • numbered from largest to smallest • include the sex chromosomes The French first described chromosomes. “p” stands for petite (or short), and “q” follows “p” in the alphabet. • “p” arm or short arm • “q” arm or long arm Chromosomes are further defined by a numbering system that: • names the individual bands (stripes) when they’re stretched out like an accordion • creates a universal language Chromosome bands are like the box cars on a train, If a band is missing or extra we generally see it under the microscope. The genes are the packages inside. By inference, if a chromosomal band is missing or extra, many genes are missing or extra. So, the 22q11.2 deletion is in the missing category in that we can sometimes see the absent material under the microscope. The 22q11.2 deletion has been identified in the majority of patients with: • DiGeorge Syndrome • Velocardiofacial Syndrome • Conotruncal Anomaly Face Syndrome • Opitz G/BBB Syndrome • Cayler Cardiofacial Syndrome This phenomenon can be likened to a group of specialized veterinarians trying to identify an elephant by each examining separate parts. For example, the specialist examining only the trunk would think an elephant is like a snake, a specialist examining only the legs would say an elephant is like tree trunks, and so on. While each was accurate in describing his own area of interest, none was able to see the big picture. So too was the case of the 22q11.2 deletion. For example, In 1965, Angelo DiGeorge, M.D. first described patients with: hypocalcemia, immune deficiency, and later, congenital heart disease. Subsequently: In 1982, Elaine Zackai, M.D. identified this patient with features of DiGeorge syndrome including: Congenital Heart Disease (Truncus arteriosus), Hypocalcemia, Immune deficiency, Cleft palate, and GI Abnormality (Jejunal web). Chromosome studies revealed: • only 45 chromosomes • including a 10;22 unbalanced translocation • resulting in a deletion in both chromosome 10 and chromosome 22 This was secondary to a balanced rearrangement in the father. Thereafter, several other patients with DiGeorge syndrome came to attention with both a 22q11.2 deletion and some other chromosomal difference, so the conclusion was drawn that DiGeorge syndrome was due to a chromosome 22q11.2 deletion. Between 1982 and 1992 visible deletions were found in 25% of patients with DiGeorge syndrome. But the puzzle remained – what about the remaining 75% of patients with no visible deletion? This led to the development of FISH probes to detect smaller deletions which were not visible under the microscope: These are referred to as submicroscopic deletions. FISH stands for fluorescence in situ hybridization. 2. What is FISH? FISH is a technique where a fluorescent probe (piece of DNA with a glowing light on it) floats around in the cell and when it finds it’s likeness it attaches and lights up. If the chromosomal material is missing there’s no glowing light – so by inference the piece is missing. It’s like a car searching for a numbered parking space – if the space isn’t present there’s no place for the car to park. Once the submicroscopic deletion was identified in DiGeorge syndrome, clinical overlap was noted with the previously mentioned diagnoses and 22q11.2 deletions were found: DiGeorge syndrome, Velocardiofacial syndrome, Conotruncal anomaly face syndrome, Autosomal dominant Opitz G/BBB syndrome,and Cayler Cardiofacial syndrome. 3. What have we learned about 22q11.2 deletion since 1992? Since the availability of the FISH probes we now know that it is The most common microdeletion syndrome with an estimated incidence of 1 in 4000 live births, and It is also the most common syndromic cause of palatal defects. The 22q11.2 deletion is so common that there have been a number of patients identified with dual diagnoses including: • Down syndrome • Marfan syndrome • Neurofibromatosis • Achondroplasia • An FGFR3 mutation (familial) • Ehlers-Danlos syndrome (familial) • Trisomy 8 mosaicism It is so common that there are affected first cousins by chance alone: • Parental deletion studies were normal • Parent of origin studies revealed that the deletion occurred in the egg cells of the unrelated mothers A large prospective cohort study at Children's Hospital of Philadelphia has observed that males and females are equally affected: 49% males and 51% females. In a recent report by Donna McGinn, MS, CGC from the Children’s Hospital of Philadelphia, unlike the early reports on patients with DiGeorge syndrome - mortality is low. Of 600 patients identified to date 4% succumbed to complications associated with the deletion. Most often related to congenital heart disease. The median age of death was 4 months. The 22q11.2 deletion is usually not “running in the family.” Only 7% of cases are familial, but an adult with the 22q11.2 deletion has a 50% (recurrence)i risk of the deletion occuring in their children.. For more information please refer to the links below or contact us 877.739.1849 or e-mail us at info@22q.org. Links

22q and You Center at CHOP, U.S.

Chromosome 22 Central

The Velo-Cardio-Facial Syndrome Education Foundation, Inc.

Max Appeal, UK

The 22q11 Group, UK

Council for Exceptional Children

American Cleft Palate - Craniofacial Association/ Cleft Palate Foundation

American Heart Association

The Genetic Education Center

VCFS Foundation Queensland, Australia

The Mayo Clinic U.S.

Immune Deficiency Foundation

Feeding Center at St. Joseph's Hosp. U.S.

The VCFS & DiGeorge List