The Gale Genetic Disorders of encyclopedia vol 1 - part 5 pps

rowed. As the left ventricle works harder to pump blood through the body, it becomes enlarged. In coarctation of the aorta, the aorta is constricted, reducing the flow of blood to the lower part of the body and increasing blood pressure in the upper body. A bicuspid aortic valve has only two flaps instead of three, which can lead to stenosis in adulthood. Subaortic stenosis is a narrowing of the left ventricle below the aortic valve, which limits the flow of blood from the left ventricle. Septal defects When a baby is born with a hole in the septum (the wall separating the right and left sides of the heart), blood leaks from the left side of the heart to the right, or from a higher pressure zone to a lower pressure zone. A major leakage can lead to enlargement of the heart and failing circulation. The most common types of septal defects are atrial septal defect, an opening between the two upper heart chambers, and ventricular septal defect, an opening between the two lower heart chambers. Ventricular septal defect accounts for about 15% of all cases of congenital heart disease in the United States. Cyanotic defects Heart disorders that cause a decreased, inadequate amount of oxygen in blood pumped to the body are called cyanotic defects. Cyanotic defects, including truncus arteriosus, total anomalous pulmonary venous return, tetralogy of Fallot, transposition of the great arteries, and tricuspid atresia, result in a blue discoloration of the skin due to low oxygen levels. About 10% of cases of congenital heart disease in the United States are tetralogy of Fallot, which includes four defects. The major defects are a large hole between the ventricles that allows oxygen- poor blood to mix with oxygen-rich blood, and narrowing at or beneath the pulmonary valve. The other defects are an overly muscular right ventricle and an aorta that lies over the ventricular hole. In transposition (reversal of position) of the great arteries, the pulmonary artery and the aorta are reversed, causing oxygen-rich blood to re-circulate to the lungs while oxygen-poor blood goes to the rest of the body. In tricuspid atresia, the baby lacks a triscupid valve and blood cannot flow properly from the right atrium to the right ventricle. Other defects Ebstein’s anomaly is a rare congenital syndrome that causes malformed tricuspid valve leaflets, which allow blood to leak between the right ventricle and the right GALE ENCYCLOPEDIA OF GENETIC DISORDERS 267 Congenital heart disease KEY TERMS Aorta—The main artery located above the heart which pumps oxygenated blood out into the body. Many congenital heart defects affect the aorta. Congenital—Refers to a disorder which is present at birth. Cyanotic—Marked by bluish discoloration of the skin due to a lack of oxygen in the blood. It is one of the types of congenital heart disease. Ductus—The blood vessel that joins the pulmonary artery and the aorta. When the ductus does not close at birth, it causes a type of congenital heart disease called patent ductus arteriosus. Electrocardiograph (ECG, EKG)—A test used to measure electrical impulses coming from the heart in order to gain information about its structure or function. Hypoplastic—Incomplete or underdevelopment of a tissue or organ. Hypoplastic left heart syndrome is the most serious type of congenital heart disease. Neuchal translucency—A pocket of fluid at the back of an embryo’s neck visible via ultrasound that, when thickened, may indicate the infant will be born with a congenital heart defect. Septal—Relating to the septum, the thin muscle wall dividing the right and left sides of the heart. Holes in the septum are called septal defects. Stenosis—The constricting or narrowing of an opening or passageway. atrium. It also may cause a hole in the wall between the left and right atrium. Treatment often involves repairing the tricuspid valve. Ebstein’s anomaly may be associated with maternal use of the psychiatric drug lithium during pregnancy. Brugada syndrome is another rare congenital heart defect that appears in adulthood and may cause sudden death if untreated. Symptoms, which include rapid, uneven heart beat, often appear at night. Scientists believe that Brugada syndrome is caused by mutations in the gene SCN5A, which involves cardiac sodium channels. Infants born with DiGeorge sequence can have heart defects such as a malformed aortic arch and tetralogy of Fallot. Researchers believe DiGeorge sequence is most often caused by mutations in genes in the region 22q11. Marfan syndrome is a connective tissue disorder that causes tears in the aorta. Since the disease also causes excessive bone growth, most Marfan syndrome patients are over six-feet-tall. In athletes, and others, it can lead to sudden death. Researchers believe the defect responsible for Marfan syndrome is found in gene FBN1, on chromosome 15. Genetic profile Scientists have made much progress in identifying some of the genes that are responsible for congenital heart defects, but others remain a mystery. When possible, genetic testing can help families determine the risk that their child will be born with a heart defect. Demographics About 32,000 infants are born every year with congenital heart disease, which is the most common birth defect. About half of these patients will require medical treatment. More than one million people with heart defects are currently living in the United States. Signs and symptoms In most cases, the causes of congenital heart disease are unknown. Genetic and environmental factors, and lifestyle habits can all be involved. The likelihood of having a child with a congenital heart disease increases if the mother or father, another child, or another relative had congenital heart disease or a family history of sudden death. Viral infections, such as German measles, can produce congenital heart disease. Women with diabetes and phenylketonuria also are at higher risk of having children with congenital heart defects. Many cases of congenital heart disease result from the mother’s excessive use of alcohol or illegal drugs, such as cocaine, while pregnant. The mother’s exposure to certain anti- convulsant and dermatologic drugs during pregnancy can also cause congenital heart disease. There are many genetic conditions, such as Down syndrome, which affect multiple organs and can cause congenital heart disease. Symptoms of congenital heart disease in general include: shortness of breath, difficulty feeding in infancy, sweating, cyanosis (bluish discoloration of the skin), heart murmur, respiratory infections that recur exces- sively, stunted growth, and limbs and muscles that are underdeveloped. Symptoms of specific types of congenital heart disease are as follows: • Patent ductus arteriosus: quick tiring, slow growth, sus- ceptibility to pneumonia, rapid breathing. If the ductus is small, there are no symptoms. • Hypoplastic left heart syndrome: ashen color, rapid and difficult breathing, inability to eat. • Obstruction defects: cyanosis (skin that is discolored blue), chest pain, tiring easily, dizziness or fainting, congestive heart failure, and high blood pressure. • Septal defects: difficulty breathing, stunted growth. Sometimes there are no symptoms. • Cyanotic defects: cyanosis, sudden rapid breathing or unconsciousness, and shortness of breath and fainting during exercise. Diagnosis Echocardiography and cardiac magnetic resonance imaging are used to confirm congenital heart disease when it is suggested by the symptoms and physical examination. An echocardiograph will display an image of the heart that is formed by sound waves. It detects valve and other heart problems. Fetal echocardiography is used to diagnose congenital heart disease in utero, usually after 20 weeks of pregnancy. Between 10 and 14 weeks of pregnancy, physicians also may use an ultrasound to look for a thickness at the nuchal translucency, a pocket of fluid in back of the embryo’s 268 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Congenital heart disease An angiogram showing a hole in the heart of a young patient. (Photo Researchers, Inc.) neck, which may indicate a cardiac defect in 55% of cases. Cardiac magnetic resonance imaging, a scanning method that uses magnetic fields and radio waves, can help physicians evaluate congenital heart disease, but is not always necessary. Physicians may also use a chest x ray to look at the size and location of the heart and lungs, or an electrocardiograph (ECG), which meas- ures electrical impulses to create a graph of the heart beat. Treatment and management Congenital heart disease is treated with drugs and/or surgery. Drugs used include diuretics, which aid the baby in excreting water and salts, and digoxin, which strength- ens the contraction of the heart, slows the heartbeat, and removes fluid from tissues. Surgical procedures seek to repair the defect as much as possible and restore circulation to as close to normal as possible. Sometimes, multiple surgical procedures are necessary. Surgical procedures include: arterial switch, balloon atrial septostomy, balloon valvuloplasty, Damus-Kaye-Stansel procedure, Fontan procedure, pulmonary artery banding, Ross procedure, shunt procedure, and venous switch or intra-atrial baffle. Arterial switch, to correct transposition of the great arteries, involves connecting the aorta to the left ventricle and connecting the pulmonary artery to the right ventricle. Balloon atrial septostomy, also done to correct transposition of the great arteries, enlarges the atrial opening during heart catheterization. Balloon valvuloplasty uses a balloon-tipped catheter to open a narrowed heart valve, improving the flow of blood in pulmonary stenosis. It is sometimes used in aortic stenosis. Transposition of the great arteries can also be corrected by the Damus-Kaye-Stansel procedure, in which the pulmonary artery is cut in two and connected to the ascending aorta and the farthest section of the right ventricle. For tricuspid atresia and pulmonary atresia, the Fontan procedure connects the right atrium to the pulmonary artery directly or with a conduit, and the atrial defect is closed. Pulmonary artery banding, narrowing the pulmonary artery with a band to reduce blood flow and pressure in the lungs, is used for ventricular septal defect, atrioventricular canal defect, and tricuspid atresia. Later, the band can be removed and the defect corrected with open-heart surgery. To correct aortic stenosis, the Ross procedure grafts the pulmonary artery to the aorta. For tetralogy of Fallot, tricuspid atresia, or pulmonary atresia, the shunt procedure creates a passage between blood vessels, sending blood into parts of the body that need it. For transposition of the great arteries, venous switch creates a tunnel inside the atria to re-direct oxygen-rich blood to the right ventricle and aorta and venous blood to the left ventricle and pulmonary artery. When all other options fail, some patients may need a heart transplant. Children with congenital heart disease require lifelong monitoring, even after successful surgery. The American Heart Association recommends reg- ular dental check-ups and the preventive use of antibiotics to protect patients from heart infections, or endocarditis. Since children with congenital heart disease have slower growth, nutrition is important. Physicians may also limit their athletic activity. Prognosis The outlook for children with congenital heart disease has improved markedly in the past two decades. Many types of congenital heart disease that would have been fatal can now be treated successfully. Research on diagnosing heart defects when the fetus is in the womb may lead to future treatment to correct defects before birth. Promising new prevention methods and treatments include genetic screening and the cultivation of cardiac tissue in the laboratory that could be used to repair congenital heart defects. Resources BOOKS Mayo Clinic Heart Book. New York: William Morrow and Company, 2000. Wild, C. L., and M. J. Neary. Heart Defects in Children: What Every Parent Should Know. Chronimed Publishing, Minneapolis, 2000. Williams, R. A. The Athlete and Heart Disease. Lippincott Williams & Wilkins, Philadelphia, 1999. PERIODICALS “Coping with Congenital Heart Disease in Your Baby.” American Family Physician 59 (April 1, 1999): 1867. Hyett, Jon, et. al. “Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks: popula- tion-based cohort study.” Lancet 318 (January 1999): 81- 85. ORGANIZATIONS American Heart Association. 7272 Greenville Ave., Dallas, TX 75231-4596. (214) 373-6300 or (800) 242-8721. inquire @heart.org. Ͻhttp://www.americanheart.orgϾ. Congenital Heart Disease Information and Resources. 1561 Clark Dr., Yardley, PA 19067. Ͻhttp://www.tchin.orgϾ. Texas Heart Institute Heart Information Service. PO Box 20345, Houston, TX 77225-0345. (800) 292-2221. Ͻhttp://www.tmc.edu/thi/his.htmlϾ. Melissa Knopper GALE ENCYCLOPEDIA OF GENETIC DISORDERS 269 Congenital heart disease I Congenital hypothyroid syndrome Definition Congenital hypothyroid syndrome is a condition in which a child is born with a deficiency in thyroid gland activity or thyroid hormone levels. Description The thyroid gland is a small gland in the front of the neck that secretes thyroid hormones called thyroxine (T4) and triiodothyronine (T3) into the bloodstream. Some of the T4 is converted into T3 by the liver and kidney. These thyroid hormones help regulate a great number of processes. A deficiency in the level of these hormones can affect the brain, heart, muscles, skeleton, digestive tract, kidneys, reproductive function, blood cells, other hormone systems, heat production, and energy metabolism. In most cases of congenital hypothyroidism, the thyroid gland is either completely absent or severely underdeveloped. Sometimes thyroid tissue is located in ectopic, or abnormal, locations along the neck. Other abnormalities can lead to congenital hypothyroidism including: • abnormal synthesis of thyroid hormones; • abnormal synthesis of thyroid-stimulating hormone (TSH) or thyrotropin-releasing hormone (TRH), which are regulatory hormones that affect the production of thyroid hormones; • abnormal response to thyroid hormones, TSH or TRH; • inadvertent administration of harmful drugs or substances to the pregnant mother, possibly resulting in temporary congenital hypothyroidism in the newborn; • dietary deficiency of iodine, a raw component vital to the manufacture thyroid hormones. Genetic profile Most causes of congenital hypothyroidism are not inherited. Some abnormalities in thyroid hormone synthesis (TSH synthesis), or the response to TSH, are inherited in autosomal recessive fashion. This means that both parents have one copy of the changed (mutated) gene but do not have the condition. Abnormal response to thyroid hormone may be an autosomal dominant condition, meaning that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome. 270 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Congenital hypothyroid syndrome KEY TERMS Congenital—Refers to a disorder which is present at birth. Ectopic—Tissue found in an abnormal location. Hypothyroid—Deficiency in thyroid gland activity or thyroid hormone levels. Jaundice—Yellowing of the skin or eyes due to excess of bilirubin in the blood. Levothyroxine—A form of thyroxine (T4) for replacement of thyroid hormones in hypothry- oidism. Myxedema—Swelling of the face, hands, feet, and genitals due to hypothyroidism. Scintigraphy—Injection and detection of radioac- tive substances to create images of body parts. Thyroxine (T4)—Thyroid hormone. Triiodothyronine (T3)—Thyroid hormone. Demographics Congenital hypothyroidism occurs in one in every 4,000 newborns in the United States. It is twice as common in girls as in boys. The condition is less common in African Americans and more common in Hispanics and Native Americans. Signs and symptoms The signs and symptoms of congenital hypothyroidism are difficult to observe because the mother passes along some of her thyroid hormones to the fetus during pregnancy. Even if the newborn is completely lacking a thyroid gland, it may not be obvious in the early stages of life. Ectopic thyroid tissue may also provide enough thyroid hormones for a short period of time. Rarely, the affected newborn will exhibit jaundice (yellow skin), noisy breathing, and enlarged tongue. If hypothyroidism continues undetected and untreated, the infant may gradually demonstrate feeding problems, con- stipation, sluggishness, sleepiness, cool hands and feet, and failure to thrive. Other signs include protruding abdomen, slow pulse, enlarged heart, dry skin, delayed teething, and coarse hair. Affected children may also have myxedema, which is swelling of the face, hands, feet, and genitals. Hypothyroidism eventually leads to marked retardation in physical growth, mental development, and sexual maturation. Diagnosis Prompt diagnosis and treatment are critical to avoid the profound consequences of hypothyroidism. The signs and symptoms of hypothyroidism are often subtle in newborns, only to manifest themselves later in life when permanent damage has been done. Before the implemen- tation of screening for hypothyroidism in the 1970s, most children with the disease suffered growth and mental retardation, as well as neurological and psychological deficits. Most cases of congenital hypothyroid syndrome are now detected by a screening test performed during a newborn’s first few days of life. Every state offers testing, and most states require it. The test for hypothyroidism is part of a battery of standard screening tests designed to diagnose important conditions. A sample of the child’s blood is analyzed for levels of thyroxine (T4), thyroid-stimulating hormone (TSH), or both, depending on the individual state or country. Some states also require a second round of screening performed one to four weeks later. Once the diagnosis of congenital hypothyroidism is made, other tests can pinpoint the nature of the abnormality. X rays of the hip, shoulder, or skull often reveal char- acteristically abnormal patterns of bone development. Scintigraphy is a method by which images of the thyroid gland and any ectopic thyroid tissue are obtained to determine if the thyroid is absent or ectopic. But treatment should not be delayed for these other tests. Early treatment offers a good probability of normal development. Treatment and management Treatment of congenital hypothyroidism requires replacement of deficient thyroid hormones with levothyroxine, an oral tablet form of T4. There is no need to GALE ENCYCLOPEDIA OF GENETIC DISORDERS 271 Congenital hypothyroid syndrome Congenital Hypothyroidism Sporadic (Gale Group) Congenital Hypothyroidism AR abnormalities in thyroid hormone syndrome, TS synthesis, or TS response (Gale Group) directly replace T3, since T4 is converted to T3 by the liver and kidney. Hypothyroid children usually require more levothyroxine per pound of body weight than hypothyroid adults do. The importance of prompt and adequate treatment cannot be overemphasized. Delays in treatment result in permanent stunting of physical, mental, and sexual development. Blood levels of T4 should be checked regularly to ensure appropriate replacement. The blood levels of TSH should also be monitored since TSH is an indicator of the effectiveness of T4 replacement. As the child develops, the physical growth rate also provides a good measure of treatment. Prognosis If congenital hypothyroidism is detected and treated early in life, the prognosis is quite good. Most children will develop normally. However, the most severely affected infants may have mild mental retardation, speech difficulty, hearing deficit, short attention span, or coordination problems. Resources BOOKS “Hypothyroidism.” In Nelson Textbook of Pediatrics, edited by Richard E. Behrman, et al. 16th ed. Philadelphia: W.B. Saunders Company, 2000. “The Thyroid.” In Cecil Textbook of Medicine, edited by Lee Goldman, et al. 21st ed. Philadelphia: W.B. Saunders Company, 2000. “Thyroid Hormone Deficiency.” In Williams Textbook of Endocrinology, edited by Jean D. Wilson, et al. 19th ed. Philadelphia: W.B. Saunders Company, 1998. ORGANIZATIONS U.S. Preventive Services Task Force, Guidelines from Guide to Clinical Preventive Services. Williams and Wilkins, 1996. Kevin O. Hwang, MD Congenital ichthyosis-mental retardation- spasticity syndrome see Sjögren Larsson syndrome Congenital isolated hemihypertrophy see Hemihypertrophy Congenital megacolon see Hirschsprung disease Congenital retinal blindness see Leber amaurosis congenita I Conjoined twins Definition Conjoined twins are an extremely rare type of identical twins who are physically joined at birth. Description Scientists believe conjoined twins form because of a delay in the fertilized egg’s division. In normal identical 272 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Conjoined twins Congenital Hypothyroidism, AD defective response to thyroid hormone post 1970 1st gen. 60y 58y 53y 54y 48y 50y 45y 43y 23y 4y 2y 25y 25y27y29y30y36y40y 20y 10y 9y 4y 6y 4y 2y 1y 28y 49y d.childhood 12y15y (Gale Group) twins, the egg splits at four to eight days after fertiliza- tion. In conjoined twins, however, the split occurs some- time after day 13. Instead of forming two separate embryos, the twins remain partially attached as they develop inside the womb. In most cases, conjoined twins do not survive more than a few days past birth because of a high rate of malformed organs and other severe birth abnormalities. However, surgical separations have been successful in conjoined twins that have a superficial physical connection. Conjoined twins are commonly referred to as Siamese twins, although this is now considered a deroga- tory term. The phrase Siamese twins originated from the famous conjoined twins Eng and Chang Bunker, who were born in Siam (Thailand) in 1811. Some conjoined twins are attached at the upper body, others may be joined at the waist and share a pair of legs. Conjoined twins often share major organs such as a heart, liver, or brain. Medical experts have identified several types of conjoined twins. They are classified according to the place their bodies are joined. Most of the terms contain the word pagus, which means “fastened” in Greek. Upper body Cephalopagus: A rare form that involves conjoined twins with fused upper bodies and two faces on opposite sides of a single head. Craniopagus: Conjoined twins with separate bodies and one shared head is a rare type and only occurs in 2% of cases. Thoracopagus: About 35% of conjoined twin births have this common form of the condition, which joins the upper bodies. These twins usually share a heart, making surgical separation nearly impossible. Lower body Ischopagus: About 6% of conjoined twins are attached at the lower half of the body. Omphalopagus: The type of conjoined twins that are attached at the abdomen and that often share a liver accounts for approximately 30% of all cases. Parapagus: About 5% of conjoined twins are joined along the side of their lower bodies. Pygopagus: About 19% of conjoined twins are joined back to back with fused buttocks. Rare types Dicephalus: Twins that share one body, but have two separate heads and necks. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 273 Conjoined twins KEY TERMS Breech delivery—Birth of an infant feet or buttocks first. Craniopagus—Conjoined twins with separate bodies and one shared head. Dicephalus—Conjoined twins who share one body but have two separate heads and necks. Fetus in fetu—In this case, one fetus grows inside the body of the other twin. Ischopagus—Conjoined twins who are attached at the lower half of the body. Omphalopagus—Conjoined twins who are attached at the abdomen. Parapagus—Conjoined twins who are joined at the side of their lower bodies. Parasitic twins—Occurs when one smaller, malformed twin is dependent on the larger, stronger twin for survival. Pygopagus—Conjoined twins who are joined back to back with fused buttocks. Thoracopagus—Conjoined twins joined at the upper body who share a heart. Zygote—The cell formed by the uniting of egg and sperm. Parasitic twins: This occurs when one smaller, malformed twin is dependent on the larger, stronger twin for survival. Fetus in fetu: In this unusual case, one fetus grows inside the body of the other twin. Genetic profile Scientists are still searching for the cause of conjoined twins. They believe a combination of genetic and environmental factors may be responsible for this rare condition. Demographics Conjoined twins occur in one out of every 50,000 births. Many such pregnancies are terminated before birth, or the infants are stillborn. Conjoined twins are always identical and of the same sex. They are more often female than male, by a ratio of 3:1. Conjoined twins are more likely to occur in Africa, India, or China than in the United States. Conjoined twins have appeared in triplet and quadruplet births, but no cases of conjoined triplets or quadruplets have ever been reported. Most parents of conjoined twins are younger than 35 years old. Signs and symptoms Approximately 50% of women who are pregnant with conjoined twins will develop excess fluid surround- ing the fetuses, which can lead to premature labor and an increased risk of miscarriage. Conjoined twins joined at the abdomen (omphalopagus) are more likely to be breech babies. In breech births, infants are born feet or buttocks first instead of head first. Most omphalopagus conjoined twins are born by cesarean section to increase their odds of survival. Conjoined twins can be born with a complication called hydrops, which causes excessive fluid to build up in an infant’s body and can be life-threatening. Those who survive past birth may experience congenital heart disease, liver or kidney disease, physical or mental dis- abilities, and intestinal blockages. Diagnosis Physicians typically try to determine if a woman is having conjoined twins at an early stage so that the parents can have an option to terminate the pregnancy if the odds of survival are low. Ultrasound imaging is a tech- nique in which high-frequency sound waves create a pic- ture of a developing fetus inside the womb and is often used to make the diagnosis. Initial diagnosis is possible at 10-12 weeks of gestation, but it is difficult to determine which body structures are involved until 20 weeks of gestation. In utero, the three-dimensional magnetic resonance imaging (MRI) test is another important diagnostic tool that helps more precisely define which body parts of the conjoined twins are connected. An abdominal x ray of the mother is used to look for connected bones in conjoined twin embryos. Treatment and management Early diagnosis is key so that families and health- care providers can begin to plan for the birth of conjoined twins. Because of the high rate of miscarriage and difficult labor, most conjoined twins are delivered by cesarean section. Some conjoined twins have survived and lived full lives without serious medical interventions. If the twins do not share a large number of organs, however, physicians typically will recommend a surgical separation. A large medical team must be assembled for a surgical separation. Physicians prefer to wait for a few months after birth, but that may not be possible if the twins are born with life-threatening congenital abnormalities. The type of surgery that is performed is determined by where the twins are connected. Doctors will often insert tissue expansion devices into the twins’ skin before the opera- tion to promote better healing at the site of separation. Conjoined twins who survive a surgical separation will have many ongoing health-care needs, from wound care to prosthetic limbs and special diets. As the twins grow up and start school, they also may need counseling to help them adjust. Prognosis The majority of conjoined twin pregnancies are not successful. However, most conjoined twins who undergo a planned surgical separation several months after birth do survive. The survival rate for conjoined twins who need an emergency separation at birth is approximately 44%. 274 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Conjoined twins These conjoined twins developed until the 17 week of pregnancy. It is difficult for conjoined twins to survive when they share the same key organs such as these siblings. (Custom Medical Stock Photo, Inc.) Resources BOOKS Martel, Joanne. Millie-Christine: Fearfully and Wonderfully Made. John F. Blair, 2000. Segal, Nancy L. Entwined Lives: Twins and What They Tell Us about Human Behavior. Dutton, 1999. Strauss, Darin. Chang and Eng. EP Dutton, 2000. PERIODICALS Johnson, Kimberly. “I Had Siamese Twins.” Ladies’ Home Journal. 110, Issue 3 (March 1993): 24-27. Paden, Cheryl Sacra, and Sondra Forsyth. “Miracle Babies.” Ladies’ Home Journal 116, Issue 11 (November 1999): 145-151. ORGANIZATIONS Center for Loss in Multiple Birth, Inc. (CLIMB). PO Box 1064, Palmer, AK 99654. (907) 222-5321. Center for Study of Multiple Birth. 334 E. Superior St., Suite 464, Chicago, IL 60611. (312) 266-9093. Ͻhttp://www .multiplebirth.comϾ. Conjoined Twins International. PO Box 10895, Prescott, AZ 86304-0895. National Organization of Mothers of Twins Clubs. PO Box 438, Thompson Station, TN 37179. (615) 595-0936. Ͻhttp://www.nomotc.orgϾ. Twins Foundation. PO Box 6043, Providence, RI 02940-6043. (401) 751-8946. Twins@twinsfoundation.com. WEBSITES Conjoined Twins fact sheet from Children’s Hospital of Columbus. Ͻwww.childrenscolumbus.org/gen/twinsfact .htmlϾ. “Conjoined Twins.” (April 30, 2001). TwinStuff.com. Ͻhttp://www.twinstuff.com/conjoined.htmϾ. OTHER Twin Falls Idaho. Videotape. Sony Pictures Classics, 1990. Melissa Knopper Cooley’s anemia see Beta-thalassemia I Corneal dystrophy Definition Corneal dystrophy is a condition that causes a layer of the cornea to cloud over and impair visual clarity. It is usually a bilateral problem, which means it occurs in both eyes equally. There are more than 20 different forms of inherited corneal dystrophies. A corneal dystrophy can occur in otherwise healthy individuals. Depending on the type of condition and the age of the individual, a corneal dystrophy may either cause no problems, moderate vision impairment, or severe difficulties that require surgery. Description The cornea is the outside layer of the eye, and comprises five layers itself, including the outer epithelium, the Bowman’s layer, the stroma, or middle, layer that takes up about 90% of the entire cornea, the Descemet’s membrane, and the endothelium. In most cases, the cen- tral (stromal) layer of the cornea is involved. Some corneal dystrophies are named after the individual who discovered them, while others are descriptive of the pattern seen with the dystrophy or the location of the disease. The key forms of corneal dystrophy are congenital hereditary endothelial dystrophy (CHED), epithelial basement membrane dystrophy, Fuchs’ endothelial dystrophy, granular dystrophy, lattice dystrophy, macular corneal dystrophy, Meesmann’s corneal dystrophy, posterior polymorphous dystrophy (PPD), and Reis- Bucklers’ dystrophy. Genetic profile Genetic alterations (mutations) causing corneal dystrophies have been mapped to 10 different chromo- somes. Some dystrophies have not yet been mapped, including Fuchs’ dystrophy. Some corneal dystrophies have the same genetic address. Mutations on the BIGH3 gene of chromosome 5q31 cause granular corneal dystrophy and Reis- Bucklers’dystrophy. Macular corneal dystrophy has been mapped to an altered gene on chromosome 16. The mutation causing congenital hereditary endothelial dystrophy has been mapped to 20p11-20q11. Lattice type I is linked to the 5q31 locus (location), while lattice type II dystrophy is linked to the 9q34 locus. Posterior polymorphous corneal dystrophy has been linked to the 20q11 locus. Most corneal dystrophies, with the exception of congenital endothelial corneal dystrophy and macular dystrophy, are autosomal dominant. In dominant disorders, a single copy of the mutated gene (received from either parent) dominates the normal gene and results in the appearance of the disease. The risk of transmitting the disorder from parent to offspring is 50% for each pregnancy. Both congenital endothelial corneal dystrophy and macular dystrophy are autosomal recessive. This means the affected person inherits the same abnormal gene for the same trait from both parents; each parent is a carrier for the disease, but they usually will have no symptoms of the disease. The risk of transmitting the disease to each pregnancy is 25%. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 275 Corneal dystrophy This disease results from excessive fluid (edema) and swelling of the basement membrane into the epithelium. Symptoms of this disease are map-like dots, opaque cir- cles, or thin lines that are formed in a swirled pattern like fingerprints. Individuals with this disorder feel like they have something irritating in the eye and experience pain and light sensitivity (photophobia). The tiny opaque collagen fibers that cause Reis- Bucklers’ dystrophy create a linear or ring-like pattern. People with this disease have recurrent painful erosions of the cornea and may also suffer from severe visual impairment. Reis-Bucklers’ is usually noticed in an infant or young child who suddenly has very red eyes. To the ophthalmologist, the cornea looks like frosted glass. This disorder may recur several times per year and dis- appear when affected individuals are in their 20s or 30s. Stromal dystrophies The primary dystrophies found in the stromal layer are granular dystrophy, lattice dystrophy, and macular dystrophy. Granular dystrophy is so named because of the small opaque areas caused by deposits of hyaline, a substance that accumulates as cells deteriorate. Lattice dystrophy is caused by deposits of amyloid, the same substance that accumulates in the brain in people with Alzheimer disease. Both granular dystrophy and lattice dystrophy have been identified in family members in Avellino, Italy, and these dystrophies are sometimes grouped together and called Avellino corneal dystrophy. Lattice and granular dystrophies can cause severe eye pain. With lattice dystrophy, by about age 40, an affected person’s vision can be very obscured and a corneal transplant is required. Endothelial dystrophies Fuchs’ dystrophy is the most common of the endothelial dystrophies and is inherited as an autosomal dominant trait. It is characterized by blurred vision, hypersensitivity to light (photophobia), and two to eight acute inflammatory attacks per year. It may also cause ulceration and erosion of the cornea. Fuchs’ can cause deterioration of endothelial cells and result in corneal guttata, which are thickenings or leakages from the Descemet’s membrane of the cornea. These guttata eventually cause edema (excessive fluid) to leak into the stromal or epithelial areas. Posterior polymorphous dystrophy (PPD), an autosomal dominant disease, also causes edema, although it affects a larger area than Fuchs’ dystrophy. It usually does not cause vision impairment. Congenital hereditary endothelial dystrophy (CHED) comprises two types. The autosomal dominant 276 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Corneal dystrophy KEY TERMS Basement membrane—Part of the epithelium, or outer layer of the cornea. Bowman’s layer—Transparent sheet of tissue directly below the basement membrane. Corneal transplant—Removal of impaired and diseased cornea and replacement with corneal tissue from a recently deceased person. Descemet’s membrane—Sheet of tissue that lies under the stroma and protects against infection and injuries. Edema—Extreme amount of watery fluid that causes swelling of the affected tissue. Endothelium—Extremely thin innermost layer of the cornea. Epithelium—The layer of cells that cover the open surfaces of the body such as the skin and mucous membranes. Hyaline—A clear substance that occurs in cell deterioration. Stroma—Middle layer of the cornea, representing about 90% of the entire cornea. Demographics The diversity of corneal dystrophies diseases makes it difficult to provide specific demographic data. Some dystrophies appear in early childhood or even infancy, such as Reis-Bucklers’ dystrophy. Others may not appear until middle age or beyond, as with Fuchs’ dystrophy. Women are at greater risk for Fuchs’ dystrophy, especially those over age 40. However, most corneal dystrophies present before age 20. Signs and symptoms The symptoms vary with the type of corneal dystrophy and the location of the site. Most experts categorize these diseases based on whether they are located on the anterior (outer) layer, stromal (middle) layer, or endothelial (inner) layer. Anterior corneal dystrophies The epithelium, or the “basement membrane,” and the Bowman’s layer together comprise the anterior, or outer part, of the cornea. Epithelial basement membrane dystrophy, also known as Cogan’s map-dot-fingerprint dystrophy, is a disorder that causes errors in refractions of the eye and may also present with microscopic cysts. [...]... abnormalities?” Journal of Pediatric Gastro and Nutrition 25, supplement 1 (19 97): 46 ORGANIZATIONS Alliance of Genetic Support Groups 43 01 Connecticut Ave NW, Suite 404, Washington, DC 20008 (202) 96 6 -5 55 7 Fax: (202) 96 6-8 55 3 Ͻhttp://www.geneticalliance.orgϾ Cornelia de Lange Syndrome Foundation, Inc 302 West Main St., Suite 10 0, Avon, CT 060 01 (860) 67 6- 816 6 (800) 22 3-8 355 Fax: (860) 67 6-8 337 March of Dimes Birth... ElastinBinding Protein.” American Journal of Human Genetics (March 2000): 85 9-8 72 Johnson, John “Costello Syndrome: Phenotype, Natural History, Differential Diagnosis, and Possible Causes.” The Journal of Pediatrics (September 19 98): 4 4 1- 448 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Lurie, I “Genetics of the Costello Syndrome.” American Journal of Medical Genetics (September 19 94): 35 8-3 59 Van Eeghen, A “Costello Syndrome:... down, further GALE ENCYCLOPEDIA OF GENETIC DISORDERS Accumulation of mucus in the smaller passageways of the lungs can plug them up, decreasing functional lung volume As the air is exhaled, much of it becomes trapped in the small pores of the lungs This leads to expansion of the lung and swollen appearance seen in the left lung above (Custom Medical Stock Photo, Inc.) hampering the movement of mucus... International Journal of Pediatric Otorhinolaryngology 31 (19 95) : 13 7–46 Kline, A.D., et al “Developmental data on individuals with the Brachmann-de Lange syndrome.” American Journal of Medical Genetics 47 (19 93): 10 53 58 Kousseff, B.G., et al “Physical growth in Brachmann-de Lange Syndrome.” American Journal of Medical Genetics 47 (19 93): 10 50 52 Mehta, A.V., et al “Occurrence of congenital heart disease... DC 20008 (202) 96 6 -5 55 7 Fax: (202) 96 6-8 55 3 Ͻhttp://www.geneticalliance.orgϾ Cri du Chat Society Dept of Human Genetics, Box 33, MCV Station, Richmond VA 23298 (804) 78 6-9 632 Cri du Chat Syndrome Support Group Ͻhttp://www.criduchat u-net.comϾ National Organization for Rare Disorders (NORD) PO Box 8923, New Fairfield, CT 06 812 -8 923 (203) 74 6-6 51 8 or (800) 99 9-6 673 Fax: (203) 74 6-6 4 81 Ͻhttp://www rarediseases.orgϾ... 458 , Crystal Lake, IL 60 014 ( 312 ) 33 7-0 742 or (888) 486 -1 2 09 aboutface2000@aol.com Ͻhttp://www.aboutface2000.orgϾ American Cleft Palate-Craniofacial Association 10 4 South Estes Dr., Suite 204, Chapel Hill, NC 27 51 4 ( 919 ) 9939044 Fax: ( 919 ) 93 3-9 604 Ͻhttp://www.cleftline.orgϾ Children’s Craniofacial Association PO Box 280297, Dallas, TX 752 4 3-4 52 2 (972) 99 4-9 902 or (800) 53 5- 3 643 contactcca@ccakids.com... Journal of Human Genetics 62 (19 98) National Eye Institute “Fact Sheet: The Cornea and Corneal Disease.” April 2000 ORGANIZATIONS Eye Bank Association of America 10 15 18 th St NW, Suite 10 10, Washington, DC 20036 (202) 77 5- 4 999 Ͻhttp://www.restoresight.org/Ͼ National Association for Visually Handicapped 22 West 21st Street, New York, NY 10 010 ( 212 ) 88 9- 314 1 Ͻhttp://www.navh.orgϾ National Eye Institute 31. .. Institute 31 Center Dr., Bldg 31, Rm 6A32, MSC 2 51 0 , Bethesda, MD 2089 2-2 51 0 (3 01) 49 6 -5 248 2020@nei.nih.gov Ͻhttp://www.nei.nih.govϾ National Organization for Rare Disorders (NORD) PO Box 8923, New Fairfield, CT 06 812 -8 923 (203) 74 6-6 51 8 or (800) 99 9-6 673 Fax: (203) 74 6-6 4 81 Ͻhttp://www rarediseases.orgϾ WEBSITES “Corneal Dystrophies.” National Eye Institute, National Institutes of Health Ͻhttp://www.nei.nih.gov/publications/... especially those of the skull Crane-Heise is distinct from aminopterin syndrome in that the mothers of infants with Crane-Heise syndrome were not exposed to aminopterin Genetic profile There are very few documented cases of CraneHeise syndrome, and therefore, little is known about the genetic basis of the disorder As of 20 01, no specific chromosome or gene location has been identified Since Crane-Heise syndrome... that the head is symmetric and abnormally small (microcephalic) Craniosynostosis KEY TERMS Acrocephalopolysyndactyly syndromes—A collection of genetic disorders characterized by cone shaped abnormality of the skull and partial fusing of adjacent fingers or toes Acrocephaly—An abnormal cone shape of the head Anterior fontanelle The soft-spot on the skull of an infant that is located in the center of the . 19 98): 4 4 1- 448. GALE ENCYCLOPEDIA OF GENETIC DISORDERS 2 85 Crane-Heise syndrome Lurie, I. “Genetics of the Costello Syndrome.” American Journal of Medical Genetics (September 19 94): 35 8-3 59 . Van. 21st Street, New York, NY 10 010 . ( 212 ) 88 9- 314 1. Ͻhttp://www.navh.orgϾ. National Eye Institute. 31 Center Dr., Bldg. 31, Rm 6A32, MSC 2 51 0 , Bethesda, MD 2089 2-2 51 0 . (3 01) 49 6 -5 248. 2020@nei.nih.gov Ladies’ Home Journal. 11 0, Issue 3 (March 19 93): 2 4-2 7. Paden, Cheryl Sacra, and Sondra Forsyth. “Miracle Babies.” Ladies’ Home Journal 11 6, Issue 11 (November 19 99): 14 5 -1 5 1. ORGANIZATIONS Center

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