Ring 18. Our Mission: To help individuals. they face so they might lead healthy, happy, and productive lives. Normal Chromosomes

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1 The Chromosome 18 Registry & Research Society Ring 18 There are five major conditions involving large changes of chromosome 18. Each of these conditions has a wide variety of characteristics. Additionally, each of the conditions can vary in severity. Although every child with a chromosome change is different, these pages provide a general idea of the medical and developmental concerns that are associated with the conditions. If you are unfamiliar with genetic concepts, we encourage you to visit our website. There, you will find several podcasts that introduce genetic concepts. Understanding basic genetics will help give the information provided here more meaning. Our Mission: To help individuals with chromosome 18 abnormalities overcome the obstacles they face so they might lead healthy, happy, and productive lives. The diagram below illustrates a pair of normal chromosome 18's. The conditions of chromosome 18 occur when there are changes in one of these two chromosomes. The five most common changes are shown below. Normal Chromosomes Trisomy 18 18q- Tetrasomy 18p Ring 18 18p- The Chromosome 18 Registry & Research Society 7155 Oakridge Drive San Antonio, Tx Phone: Administrative Director: GEllwanger@chromosome18.org Executive Director: CJTraa@chromosome18.org Page 1 office@chromosome18.org

2 Background and Genetic Basis The goal of this article is to describe the major features of ring 18. This information may help you and your health care team make decisions about how to care for a person with ring 18. As you read through this article, remember that no two people with ring 18 are exactly alike. One person may have different medical and developmental concerns from another person with ring 18. Also, remember that no one with ring 18 will have all of the features discussed below. In addition, people with ring 18 share many features with their family members. They will also have their own unique skills and abilities which you will not find in the following list. Research is critical. As we learn more about ring 18, we also learn more about how to best treat it. This will improve the health and development of people with ring 18. Background Ring 18 was first described in the 1960s. Since then, over 50 case reports have been published describing the features of ring 18. Genetic Basis of Ring 18 Typically, chromosomes look like long rods when examined under the microscope. Sometimes, one of the chromosomes is rearranged into a ring-like shape. This is called a ring chromosome. A ring chromosome forms when the end of one of the chromosome arms fuses with the end of the other arm. For more information about basic genetic concepts, please visit our website at A ring chromosome occurs when the two ends of the chromosome fuse to form a ring. Typically, this means that the end of the long arm as well as the end of the short arm of the chromosome are missing. Nearly all cases of ring chromosomes, pieces of the long and the short arms of the chromosome are missing. These pieces may be large or very small. They may or may not contain genes that are important in growth and development. Ring 18 is different from other chromosome 18 changes (18q-, 18p-, tetrasomy 18p) in that mosaicism is fairly common in individuals with ring 18. Mosaicism occurs when different cells have different numbers or arrangements of chromosomes. For example, in the case of ring 18, some of the body s cells may have the ring chromosome while other cells do not. office@chromosome18.org Page 2

3 Characteristics of Ring 18 As discussed previously, most people with ring 18 are missing a piece of the long arm of chromosome 18 as well as a piece of the short arm. Therefore, they can have features of both 18p as well as 18q-. The features that are discussed in this article have been described in the medical literature in individuals with ring 18. Development In most individuals, ring 18 changes the way the brain develops and works. Infants, toddlers and young children with ring 18 may develop more slowly than those without ring 18. For example, it may take a little longer for them to roll over, sit, crawl, and walk. It may also take longer for them to reach for and grab toys, hold a bottle, and to feed themselves. Language skills may also develop later than their peers. Almost all children with ring 18 will require some type of therapy, such as speech, occupational, or physical therapy. People with ring 18 usually have some cognitive disability, though the degree of impairment varies among individuals. Based on literature reports, people with ring 18 appear to have IQ scores ranging from mild to severe mental impairment. Again, it is important to remember that every person with ring 18 is different. Some may be more severely affected than others. At this time, we cannot predict exactly how ring 18 will affect a child s development. Holoprosencephaly Some people with ring 18 have a condition called holoprosencephaly. Holoprosencephaly is a type of birth defect in which the brain fails to divide into two separate halves during early embryonic development. This term includes a wide range of severity. In some babies, this condition is so severe that they do not survive in the womb or they may die shortly after birth. Other individuals may have much more mild forms of the condition. For example, an MRI may show that their brain has some other types of changes, such as a missing corpus callosum (the connection between the two halves of the brain). There may be changes in the facial features as well, such as a cleft lip and palate or hypotelorism (eyes that are closely set to one another). Another minor feature of holoprosencephaly is a single incisor (front tooth) located at the midline of the mouth. Individuals with holoprosencephaly may have a number of different health concerns. Many have developmental delays. Seizures and hydrocephalus (build-up of fluid in the brain) may also occur. Some people with holoprosencephaly may have hormone problems caused by a change in the structure of the pituitary gland in the brain. To learn more about holoprosencephaly, you can visit the National Institute of Neurological Disorders and Stroke ( Page 3 office@chromosome18.org

4 Neurological Changes The Chromosome 18 Registry & Research Society People with ring 18 may have neurological problems that are unrelated to the presence or absence of holoprosencephaly. They may have low muscle tone (hypotonia). Changes in muscle tone can lead to other difficulties. For example, infants with low muscle tone may have difficulty eating because the muscles surrounding the mouth are weak. They may have slower or absent reflexes. In a minority of cases, a person with ring 18 may develop seizures. If there are neurological concerns, a person should be referred to a neurologist for a complete evaluation. Eyes and Vision Vision problems are often found in people with ring 18. Strabismus is fairly common in people with ring 18. Strabismus occurs when the movements of the eyes are not coordinated with one another. This is frequently referred to as being cross-eyed. Sometimes, people with ring 18 have nystagmus, or involuntary eye movements. Near-sightedness and far-sightedness also happen fairly frequently in people with ring 18. Hearing Loss Some individuals with ring 18 have hearing loss. In some of these cases, the hearing loss is caused by ear canals that are narrow or end before they reach the ear drum. Because there is a risk for hearing loss, people with ring 18 should have regular hearing screening. This will help find and treat hearing loss early. Heart Heart defects are found in about 30-40% of babies with ring 18. There are several different kinds of heart defects that have been diagnosed in babies with ring 18. The most common type of heart defect appears to be a septal defect. This means that there is a defect in the wall that separates the left and right sides of the heart. Because heart defects are more common in babies with ring 18 than in those without ring 18, and echocardiogram (ultrasound of the heart) may be recommended to look for defects. Gastrointestinal and Other Abdominal Changes A small minority of individuals with ring 18 develop a hernia at some point in their life. A hernia occurs when some organs, often the intestines, push outside of the abdomen. The most common types of hernias are umbilical hernias and inguinal hernias. An umbilical hernia occurs when the intestines push out through the abdominal wall. An inguinal hernia occurs when the intestines protrude through the lower abdominal wall into the groin area. In many cases, no treatment is required. However, in some individuals, surgery is necessary to repair the hernia. Genitourinary Changes Several different kinds of kidney problems have been described in children with ring 18. For example, they may have a small or a missing kidney. Urine may not be eliminated correctly, resulting in an abnormal accumulation or urine in the urinary system. This may lead to infections in the urinary tract. Males with ring 18 may have some changes in the genital region. The testicles may not be fully descended (cryptorchidism). The opening of the urethra may not be at the end of the penis (hypospadias). A doctor may order an abdominal ultrasound to rule out structural changes in the kidney. A test called a voiding cystourethrogram may be ordered to examine the flow of urine in the urinary tract. In some instances, surgery is required to correct cryptorchidigm or hypospadias. office@chromosome18.org Page 4

5 Musculoskeletal Problems People with ring 18 frequently have problems with their feet or back. For example, they may have a club foot or other kind of foot abnormality. They may also develop scoliosis, or curvature of their spine. People with foot or spinal changes may be referred to an orthopedic specialist by their regular medical doctor. Braces and inserts, surgery, and therapy may help in addressing orthopedic concerns. Growth Children and adults may have changes in their growth patterns. Children with ring 18 are often small for their age. Growth hormone deficiency has been identified in some people with ring 18, though the precise frequency of this finding is unknown. There have been two cases (<5% of all cases) reported in the literature. However, not all cases reported in the literature have been tested for growth hormone deficiency. Thus, the incidence of growth hormone deficiency is likely higher. If there is a concern regarding growth, a person can see a pediatric endocrinologist to rule out growth hormone deficiency. Drs. Jannine Cody and Daniel Hale have written an article for the Chromosome 18 Registry & Research Society about growth hormone deficiency in children with chromosome 18 abnormalities. In addition to short stature, many people with ring 18 have microcephaly, or a head size that falls below the 3rd percentile. Facial Features People with ring 18 may have facial features that are slightly different from other family members. These changes do not affect a child s health or development. They are simply small differences that might be noted by a doctor. For example, people with ring 18 may have ears that are lower-set and look slightly different from a typical ear. They may have an extra fold of skin covering the corner of the eye or their eyes might be placed further apart than people without ring 18. The lower jaw may be slightly smaller than in people without ring 18. Although people with ring 18 may have facial features in common with one another, it is important to remember that they also have features in common with their family members. Family Planning and Genetic Counseling Many parents wonder, If we have another child, what is the chance that our next child will have ring 18? The answer to this question is complicated and depends on whether a chromosome change has been identified in one of the parents. In most cases, neither parent has a chromosome change. In this situation, the chance that a couple will have another child with ring 18 is very low. In a small number of families, one parent also has a chromosome change. If a parent has a chromosome change, there is a significant chance that they will have a child with a chromosome change. If you have questions about the implications of a chromosome change for other family members, we recommend contacting a genetics provider. Page 5 office@chromosome18.org

6 For Additional Information The information provided here is general information based on the literature as well as the experiences in the Chromosome 18 Clinical Research Center. However, every person with ring 18 is different. Therefore, this information should not replace professional medical advice, diagnosis, or treatment. If you have questions or concerns, you may find it helpful to talk with a clinical geneticist or genetic counselor. You can locate a genetics provider at one of these sites: GeneTests Clinic Directory ( National Society of Genetic Counselors ( Selected References Ansurewil SS, McDermott A, Savage DCL (1988). Growth hormone, suspected gonadotrophin deficiency, and ring 18 chromosome. Arch Dis Child 63: Christensen KR, Friedrich U, Jacobsen P, Jensen K, Nielsen J, Tsuboi T (1970).. Ring chromosome 18 in mother and daughter. J Ment Defic Res 14: Fryns JP, Kleczkowska A, Smeets E, van den Berghe H (1992). Transmission of ring chromosome 18 46,XX/46,XX,r(18) mosaicism in a mother and ring chromosome 18 syndrome in her son. Ann Gene 35(2): Fryns JP, Kleczkowska A (1992). Autism and ring chromosome 18 mosaicism. Clin Genet 42:55. Meloni A, Boccone L, Angius L, Loche S, Falchi AM, Cao A (1994). Hypothalamic growth hormone deficiency in a patient with ring chromosome 18. Eur J Pediatr 153: Yanoff M, Rorke LB, Niederer BS (1970). Ocular and Cerebral abnormalities in chromosome 18 deletion defect. Am J Opthalmol 70: Officers President Jannine D. Cody, Ph.D. Vice President for Member Relations Catherine Burzio Vice President for Public Relations Ben Flowe, Jr. Secretary Kristen Earl Treasurer Denise Parker Staff Executive Director Claudia Traa Administrative Director Gloria Ellwanger Board of Directors If you found this information helpful, or would like to learn more about the Chromosome 18 Registry & Research Society, we encourage you to become a member of our organization. To become a member, visit our website at or call us at With your help, we will achieve our mission : To help individuals with chromosome 18 abnormalities overcome the obstacles they face so they might lead healthy, happy, and productive lives. office@chromosome18.org Page 6