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Gale Encyclopedia of Genetic Disorder / Gale Encyclopedia of Genetic Disorders, Two Volume Set - Volume 1 - A-L - I

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Arthropathy-camptodactyly syndrome

K E Y T E R M S

Allele—One of two or more alternate forms of a gene.

Arthropathy—Any disease or disorder that affects joints.

Camptodactyly—A condition characterized by the bending of one or more fingers.

Chromosome—A microscopic thread-like structure found within each cell of the body and consists of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Changes in either the total number of chromosomes or their shape and size (structure) may lead to physical or mental abnormalities.

Congenital disorder—Refers to a disorder which is present at birth.

Deoxyribonucleic acid (DNA)—The genetic material in cells that holds the inherited instructions for growth, development, and cellular functioning.

Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.

Haplotype—The set of alleles on one chromosome.

Locus—The physical location of a gene on a chromosome.

I Arthropathy-camptodactyly

syndrome

Definition

Arthropathy-camptodactyly syndrome is a disorder affecting the joints of the fingers. Arthropathy refers to a disease or disorder affecting a joint, and camptodactyly is a congenital condition, meaning present at birth, characterized by the bending of one or more fingers.

Description

In people with arthropathy-camptodactyly syndrome, one or more fingers are bent. Other joints may be affected as well—some children with arthropathy-camp-

todactyly syndrome also have swollen knees and ankles, and hip pain.

Problems with the pericardium, the sac that surrounds the heart, are also common in children with arthropathy-camptodactyly syndrome. In many cases the pericardium is removed, a surgical procedure called pericardiectomy.

Genetic profile

Arthropathy-camptodactyly syndrome typically occurs in children (both male and female) whose parents are related by blood. In one case, it was determined that the parents of children with arthropathy-camptodactyly syndrome shared the haplotype A1-Bw21. The gene map locus 1q24-q25 is also implicated.

Demographics

As of 2000, cases of arthropathy-camptodactyly syndrome have been diagnosed in Canada, India, Mexico, Newfoundland, Pakistan, Saudi Arabia, and Turkey, as well as in African Americans.

Signs and symptoms

People with arthropathy-camptodactyly syndrome have a bend in the joint of one or more fingers. Other symptoms include swollen knees and ankles, and hip pain.

Inflammation of the sac lining the heart (pericarditis) is another observed symptom, often accompanied by chest pain. The pain is usually sharp, and felt behind the breast bone (sternum).

Diagnosis

Aside from the physical observation of bent fingers, no test is presently available to confirm diagnosis.

Treatment and management

Surgery can correct the bent fingers disorder that characterizes arthropathy-camptodactyly syndrome. Removal of the tendon sheaths in the affected fingers can help to keep them mobile. Removal of the membranes surrounding a joint (synovectomy) of other body joints, such as knees, can also help maintain mobility.

In at least one case, a bent finger straightened without intervention.

Pericardiectomy is often performed to relieve the pericarditis often associated with the disorder.

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Prognosis

As of 2000, case studies show that children with arthropathy-camptodactyly syndrome have lived into their teens. There is reason to believe that with the proper treatment, the disorder is not life-shortening.

Resources

PERIODICALS

Athreya, B. H., and H. R. Schumacher. “Pathologic features of a familial arthropathy associated with congenital flexion contractures of fingers.” Arthritis and Rheumatism 21 (1978): 429-437.

Bahabri, S. A., et al. “The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1.” Arthritis and Rheumatism 41 (1998): 730-735.

Bulutlar, G., H. Yazici, H. Ozdogan, and I. Schreuder. “A familial syndrome of pericarditis, arthritis, camptodactyly, and coxa vara.” Arthritis and Rheumatism 29 (1986): 436-438.

Martin, J. R., et al. “Congenital contractural deformities of the fingers and arthropathy.” Annals of the Rheumatic Diseases 44 (1985): 826-830.

Suwairi, W. M., et al. “Autosomal recessive camptodactyly- arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to chromosome 1q25-31.”

(Abstract) American Journal of Human Genetics 61 (supplement, 1997): A48.

WEBSITES

“Entry 208250: Arthropathy-Camptodactyly Syndrome.” National Center for Biotechnology Information, Online

Mendelian Inheritance in Man http://www.ncbi.nlm.nih

.gov/htbin-post/Omim/dispmim?208250 .

Sonya Kunkle

I Asperger syndrome

Definition

Asperger syndrome (AS), which is also called Asperger disorder or autistic psychopathy, belongs to a group of childhood disorders known as pervasive developmental disorders (PDDs) or autistic spectrum disorders. AS was first described by Hans Asperger, an Austrian psychiatrist, in 1944. Asperger’s work was unavailable in English before the mid-1970s; as a result, AS was often unrecognized in English-speaking countries until the late 1980s. Before the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV 1994), there was no official definition of AS.

K E Y T E R M S

Autistic psychopathy—Hans Asperger’s original name for Asperger syndrome. It is still used occasionally as a synonym for the disorder.

Gillberg’s criteria—A six-item checklist for Asperger syndrome developed by Christopher Gillberg, a Swedish researcher. It is widely used as a diagnostic tool.

High-functioning autism (HFA)—A subcategory of autistic disorder consisting of children diagnosed with IQs of 70 or higher.

Nonverbal Learning Disability (NLD)—A learning disability syndrome identified in 1989 that may overlap with some of the symptoms of Asperger syndrome.

Pervasive developmental disorder (PDD)—The term used by the American Psychiatric Association for individuals who meet some but not all of the criteria for autism.

Description

Children with AS learn to talk at the usual age and often have above-average verbal skills. They have normal or above-normal intelligence and the ability to take care of themselves. The distinguishing features of AS are problems with social interaction, particularly reciprocating and empathizing with the feelings of others; difficulties with nonverbal communication (e.g., facial expressions); peculiar speech habits that include repeated words or phrases and a flat, emotionless vocal tone; an apparent lack of “common sense”; a fascination with obscure or limited subjects (e.g., doorknobs, railroad schedules, astronomical data, etc.) often to the exclusion of other interests; clumsy and awkward physical movements; and odd or eccentric behaviors (hand wringing or finger flapping; swaying or other repetitious whole-body movements; watching spinning objects for long periods of time).

Genetic profile

There is some indication that AS runs in families, particularly in families with histories of depression and bipolar disorder. Asperger noted that his initial group of patients had fathers with AS symptoms. Knowledge of the genetic profile of the disorder, however, is quite limited as of 2001.

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Asperger syndrome

Demographics

Although the incidence of AS has been variously estimated between 0.024% and 0.36% of the general population in North America and northern Europe, further research is required to determine its true rate of occurrence—especially because the diagnostic criteria have been defined so recently. In addition, no research regarding the incidence of AS has been done on the populations of developing countries.

AS appears to be much more common in boys. One Swedish study found the male/female ratio to be 4:1. Dr. Asperger’s first patients were all boys, but girls have been diagnosed with AS since the 1980s.

Signs and symptoms

About 50% of patients with Asperger syndrome have a history of oxygen deprivation during the birth process, which has led to the hypothesis that the syndrome is caused by damage to brain tissue before or during childbirth. Another cause that has been suggested is an organic defect in the functioning of the brain. Behavioral symptoms that are considered diagnostically significant are described in the next section.

Diagnosis

As of 2001, there are no blood tests or brain scans that can be used to diagnose AS. Until DSM-IV (1994), there was no “official” list of symptoms for the disorder, which made its diagnosis both difficult and inexact. Although most children with AS are diagnosed between five and nine years of age, many are not diagnosed until adulthood. Misdiagnoses are common; AS has been confused with such other neurological disorders as Tourette’s syndrome, or with Attention-Deficit Disorder (ADD), Oppositional Defiant Disorder (ODD), or ObsessiveCompulsive Disorder (OCD). Some researchers think that AS overlaps with some types of learning disability, such as the Nonverbal Learning Disability (NLD) syndrome identified in 1989.

The inclusion of AS as a separate diagnostic category in DSM-IV was justified on the basis of a large international field trial of over a thousand children and adolescents. Nevertheless, the diagnosis of AS is also complicated by confusion with such other diagnostic categories as “high-functioning (IQ 70) autism,” or HFA, and “schizoid personality disorder of childhood.” With regard to the latter, AS is not an unchanging set of personality traits but has a developmental dimension. AS is distinguished from HFA by the following characteristics:

Later onset of symptoms (usually around three years of age)

Early development of grammatical speech; the AS child’s verbal IQ is usually higher than performance IQ (the reverse being the case in autistic children)

Less severe deficiencies in social and communication skills

Presence of intense interest in one or two topics

Physical clumsiness and lack of coordination

Family is more likely to have a history of the disorder

Lower frequency of neurological disorders

More positive outcome in later life.

DSM-IV criteria for Asperger syndrome

DSM-IV specifies six diagnostic criteria for AS:

The child’s social interactions are impaired in at least two of the following ways: markedly limited use of nonverbal communication; lack of age-appropriate peer relationships; failure to share enjoyment, interests, or accomplishment with others; lack of reciprocity in social interactions.

The child’s behavior, interests, and activities are characterized by repetitive or rigid patterns, such as an abnormal preoccupation with one or two topics, or with parts of objects; repetitive physical movements; or rigid insistence on certain routines and rituals.

The patient’s social, occupational, or educational functioning is significantly impaired.

The child has normal age-appropriate language skills.

The child has normal age-appropriate cognitive skills, self-help abilities, and curiosity about the environment.

The child does not meet criteria for another specific PDD or schizophrenia.

Other diagnostic scales and checklists

Other instruments that have been used to identify children with AS include Gillberg’s criteria, a six-item list compiled by a Swedish researcher that specifies problems in social interaction, a preoccupying narrow interest, forcing routines and interests on the self or others, speech and language problems, nonverbal communication problems, and physical clumsiness; and the Australian Scale for Asperger Syndrome, a detailed multi-item questionnaire developed in 1996.

Brain imaging findings

As of 2001, only a few structural abnormalities of the brain have been linked to AS. Findings include abnormally large folds in the brain tissue in the left frontal region, abnormally small folds in the operculum (a lid-

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like structure composed of portions of three adjoining brain lobes), and damage to the left temporal lobe. The first single photon emission tomography (SPECT) study of a patient found lower than normal blood supply in the left parietal area of the brain. Brain imaging studies on a larger sample of patients with AS is the next stage of research.

Treatment and management

As of 2001, there is no cure for AS and no prescribed regimen for all affected patients. Specific treatments are based on the individual’s symptom pattern.

Medications

The drugs that are recommended most often for children with AS include psychostimulants (methylphenidate, pemoline), clonidine, or one of the tricyclic antidepressants (TCAs) for hyperactivity or inattention; beta blockers, neuroleptics, or lithium for anger or aggression; selective serotonin reuptake inhibitors (SSRIs) or TCAs for rituals and preoccupations; and SSRIs or TCAs for anxiety symptoms. One alternative herbal remedy that has been tried with some patients is St. John’s wort.

Psychotherapy

Individuals with Asperger syndrome often benefit from psychotherapy, particularly during adolescence, in order to cope with depression and other painful feelings related to their social difficulties.

Educational considerations

Most patients with AS have normal or above-normal intelligence, and are able to complete their education up through the graduate or professional school level. Many are unusually skilled in music or good in subjects requiring rote memorization. On the other hand, the verbal skills of children with AS frequently cause difficulties with teachers, who may not understand why these “bright” children have social and communication problems. Some children are dyslexic; others have difficulty with writing or mathematics. In some cases, children with AS have been mistakenly put in special programs either for children with much lower levels of functioning, or for children with conduct disorders. Children with AS do best in structured learning situations in which they learn problem-solving and life skills as well as academic subjects. They frequently need protection from the teasing and bullying of other children, and often become hypersensitive to criticism by their teenage years.

Employment

Adults with AS are productively employed in a wide variety of fields. They do best, however, in jobs with regular routines or jobs that allow them to work in isolation. Employers and colleagues may need some information about Asperger syndrome in order to understand the employee’s behavior.

Prognosis

AS is a lifelong but stable condition. The prognosis for children with AS is generally good as far as intellectual development is concerned, although few school districts as of 2001 are equipped to meet their special social needs. In addition, some researchers think that people with AS have an increased risk of becoming psychotic in adolscence or adult life.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Washington, DC: American Psychiatric Association, 1994.

Thoene, Jess G., editor. Physicians’ Guide to Rare Diseases.

Montvale, NJ: Dowden Publishing Company, 1995.

ORGANIZATIONS

Autism Research Institute. 4182 Adams Ave., San Diego, 92116. Fax: (619) 563-6840.

Families of Adults Afflicted with Asperger’s Syndrome (FAAAS). PO Box 514, Centerville, MA 02632.http://www.faaas.org .

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. http://www

.rarediseases.org .

Yale-LDA Social Learning Disabilities Project. Yale Child Study Center, 230 South Frontage Road, New Haven, CT 06520-7900. (203) 785-3488. http://info.med.Yale.edu/ chldstdy/autism .

WEBSITES

Asperger’s Disorder Home Page, maintained by Kaan Ozbayrak, MD. http://www.ummed.edu/pub/o/ozbayrak/ autasp .

Center for the Study of Autism Home Page, maintained by Stephen Edelson, PhD. http://www.autism.org/asperger

.html .

O.A.S.I.S. (Online Asperger Syndrome Information and

Support). http://www.udel.edu/bkirby/asperger/ .

Rebecca J. Frey, PhD

syndrome Asperger

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Asplenia

I Asplenia

Definition

The term “asplenia” literally means absent spleen. However, in the condition asplenia, the spleen is not always absent. Sometimes the spleen is present, but not fully developed (hypoplastic). In asplenia, the spleen is typically not the only organ affected. Individuals with this condition often have problems with other organs and organ systems. A related condition is polysplenia. The term “polysplenia” literally means multiple spleens. Both of these conditions affect the placement and development of the organs inside the body. There is controversy over whether asplenia and the other syndromes, like polysplenia, that affect the position of the internal organs are actually different aspects of the same condition, referred to as Heterotaxy syndrome, or separate and distinct syndromes. As of 2001, this issue has not been resolved.

Asplenia is just one of the names used to refer to this condition. Other names include Ivemark syndrome, right isomerism sequence, bilateral right-sideness sequence, splenic agenesis syndrome, and asplenia with cardiovascular anomalies.

Description

The human body can be viewed as having a right side and a left side. Normally, inside the human body, the right side and the left side are different with respect to the presence of certain organs. Several organs inside the body are placed asymmetrically, meaning that one organ may be located on one side of the body, but not the other. Furthermore, there are some organs that are found on both sides of the body, but have differences that distinguish the right organ from its partner on the left side. In asplenia, the position, location, appearance, and performance of some of the internal organs are altered. Organs can often be found on the wrong side of the body and/or have structural defects. Furthermore, in most people the right and left organs are different; in people with asplenia, both organs may appear to be structured the same.

Genetic profile

In most families, asplenia is believed to occur sporadically. In other words, it occurs for the first time in a family and has no known or identifiable pattern of inheritance.

There have been several couples described in the medical literature who have more than one child diagnosed with asplenia. In several of these families, the parents were related to each other. Individuals who are related to each other are more likely to carry some of the

same non-working genes. Therefore, these families illustrate the possibility that asplenia can be inherited in an autosomal recessive manner. Individuals who have an autosomal recessive condition have both genes in a pair that do not work as expected or are missing, thereby causing the disease. One non-working gene is inherited from the mother and the other is inherited from the father. These parents are called carriers of that condition. When two people are known carriers for an autosomal recessive condition, they have a 25% chance with each pregnancy of having a child affected with the disease.

There are a few families where asplenia appears to be inherited in an autosomal dominant or X-linked manner. In autosomal dominant inheritance, only one gene in the pair needs to be abnormal to cause symptoms of the condition. In families where asplenia appears to be inherited in an autosomal dominant manner, family members who carry the same non-working gene can have different symptoms and the severity of the condition may vary. In autosomal dominant inheritance, if an individual carries the non-working gene, he or she has a 50% chance of passing the gene on with each pregnancy.

In families where asplenia appears to be inherited in a X-linked manner, the gene causing the condition is located on the X chromosome. Since women have two X chromosomes, if a woman inherits the non-working gene on one of her X chromosomes, typically she will not have any symptoms of asplenia or will have a milder form of the condition. A woman who carries the X-linked form of asplenia will have a 50% chance of passing that non-working gene on with each pregnancy.

Since men tend to have one Y chromosome and one X chromosome, if it is a son that inherits the non-working gene, he will be affected with the condition. Men who have a X-linked form of asplenia will always pass their X chromosome containing the non-working gene on to all of their daughters, who would be carriers of the condition. In these families, asplenia will never be passed from the father to the son, since men give their sons a Y chromosome. If a woman who carries a X-linked condition passes the X chromosome containing the non-working gene to a daughter, then that daughter will be a carrier like her mother.

The pattern of inheritance of asplenia in a family is usually not obvious when there is only one individual diagnosed with the condition. Based on the families and studies performed on asplenia, the chance of a couple who have one child with asplenia having another child with the condition is approximately 5% or less. This chance may be higher if it is determined that asplenia is part of Heterotaxy syndrome, since there are a wider range of symptoms associated with that condition. Furthermore, if more than one family member has the diagnosis of asplenia, the chance of it occurring again in

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K E Y T E R M S

Anomalous—Irregular or different from normal.

Anomalous venous return—Normally, the veins that bring blood containing oxygen from the lungs to the heart (called pulmonary veins) are connected to the left atrium. In this situation, the pulmonary veins are connected to the right atrium.

Asplenia—The absence of the spleen in the body.

Atria/Atrium—The upper chamber of the heart. Typically, there are two atrias, one on the right side and one on the left side of the heart.

Atrial septal defect—An opening between the right and left atria of the heart.

Congenital—Refers to a disorder which is present at birth.

Cyanosis—The bluish color of the skin that occurs when there is very low oxygen in the blood that is being transported throughout the body.

Echocardiography/Echocardiogram—An ultrasound examination targeted at the heart and performed by a cardiologist or an individual trained at detecting differences in the structure of the heart.

Isomerism—Refers to the organs that typically come in pairs, but where the right organ is structurally dif-

ferent from the left organ. In a condition like asplenia, the organs are identical.

Malrotation—An abnormality that occurs during the normal rotation of an organ or organ system.

Pulmonary atresia—When there is no valve between the right ventricle and the pulmonary artery (the artery leading from the heart to the lungs). In the absence of this valve, the blood does not flow into the lungs well.

Pulmonary stenosis—Narrowing of the pulmonary valve of the heart, between the right ventricle and the pulmonary artery, limiting the amount of blood going to the lungs.

Syndrome—A group of signs and symptoms that collectively characterize a disease or disorder.

Transposition of the great arteries—A reversal of the two great arteries of the heart, causing blood containing oxygen to be carried back to the lungs and blood that is lacking in oxygen to be transported throughout the body.

Truncus arteriosus—Having only one artery coming from the heart instead of two. Often there is a ventricular septal defect (VSD) present.

Ventricular septal defect (VSD)—An opening between the right and left ventricles of the heart.

the family is based on the pattern of inheritance that the condition appears to be following.

Since asplenia appears to be inherited in different ways, it is theorized that there may be several different genes that could cause asplenia. This means that some families may have asplenia caused by one specific nonworking gene, but in other families, a different non-work- ing gene could cause the same condition to occur. As of 2001, the exact genes involved in causing asplenia have not been identified. However, there is ongoing research to identify the genes involved with this condition.

Demographics

It is estimated that the incidence of asplenia is low, approximately one in 10,000 to one in 20,000 live births. More males are affected with the condition than females. Asplenia also accounts for 1-3% of all congenital heart defects. Asplenia does not appear to occur more frequently in certain ethnic groups.

Signs and symptoms

Almost all individuals with asplenia have an abnormal or absent spleen. However, there are other organs and organ systems that can be affected.

Abdominal organs

SPLEEN As the name of the condition implies, the spleen is always affected in asplenia. The spleen in individuals with asplenia is either absent or does not develop completely (hypoplastic spleen). Since the spleen is involved in the body’s immune system, these infants can have an abnormal immune system, which increases their risk for developing an infection.

DIGESTIVE TRACT DISORDERS There are several abnormalities that can occur with the digestive tract in individuals with asplenia. The most common digestive tract disorder associated with asplenia is malrotation of the intestine. Sometimes a digestive tract problem will present with symptoms of an obstruction in the digestive system, requiring emergency surgery.

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Asplenia

STOMACH Most individuals with asplenia have their stomach located on the right side or in the center of the body instead of the left. In addition, individuals with asplenia can have a “twisted” stomach that could result in an obstruction in their digestive system and impair the blood supply to the stomach (gastric volvulus).

LIVER Normally, the liver is located on the right side of the body and the shape of the liver is not symmetrical. In asplenia, there can be isomerism of the liver—it can be located in the middle of the body, or located on the left side with the larger half of the liver located in the upper left side of the abdominal area.

GALLBLADDER The gallbladder may also be located in the middle of the body in individuals with asplenia.

Heart

Many infants with asplenia first present with cyanosis and severe respiratory distress. These are symptoms often seen in individuals who have a heart defect. Most individuals with asplenia have a defect in the structure and/or the position of their heart.

Typically, the heart is divided into two sides, a left and right, with each side containing two chambers, called ventricle and atrium. The left and right sides of the heart are different from each other in their structure and function. The job of the right side of the heart is to pump blood to the lungs to receive oxygen. The job of the left side of the heart is to receive the oxygenated blood from the lungs and pump it to the rest of the body. In asplenia, sometimes the structures of the right side of the heart are duplicated on the heart’s left side.

A common heart defect often seen in asplenia is anomalous pulmonary venous return, which occurs when the pulmonary veins (the blood vessels that carry blood containing oxygen from the lungs to the heart) are connected to the right atrium instead of the left atrium. This causes the oxygenated blood to be pumped back to the lungs instead of the body. Sometimes, there is a hole between the right and left atrium (called atrial septal defect or ASD) that allows some of the oxygenated blood into the left atrium and pumped to the rest of the body.

Other heart defects frequently seen in individuals with asplenia include: common atrioventricular canal, common atrial canal, persistent truncus arteriosus, pulmonary stenosis or atresia, single ventricle in the heart, and transposition of the great arteries. Often there is more than one heart defect present. Furthermore, in many individuals with asplenia, the heart is located on the right side of the body instead of the left.

Lungs

Normally, the lungs are divided into lobes. The lung on the right side of the body usually has three lobes and the left lung typically has two lobes. In asplenia, each lung usually has three lobes.

There can be abnormalities in other systems of the body as well, but they are not often seen in most individuals with asplenia. Other abnormalities associated with asplenia include kidney anomalies, extra fingers and toes, scoliosis, facial abnormalities, and central nervous system anomalies.

Diagnosis

The diagnosis of asplenia is typically made by imaging studies. An echocardiogram of the heart can help identify any structural abnormalities and its exact position within the body. A chest x ray can also be used to locate the position of the heart and some of the other organs in the body. Ultrasound and CT examinations can also help determine if there are any malformations with the abdominal organs, the position of the stomach, the presence, appearance, and number of spleens, and how many lobes each lung has. While a MRI can also detect the presence and position of organs inside the body, it is less commonly used because of the need for sedation and the high cost of the test, especially in children.

Testing for the presence of Heinz and Howell-Jolly bodies in the blood has been suggested as a method to screen for an absent spleen. Howell-Jolly bodies are unique cells that tend to be present in the blood of individuals who do not have a spleen, but they can also be seen in the blood of individuals who have certain types of anemia. Therefore, this test should not be used as the sole diagnostic test for an absent spleen.

Some of the abnormalities seen in asplenia can be detected prenatally. Often the position of the heart and some of the heart defects can be diagnosed by fetal echocardiogram (an ultrasound examination of the fetal heart) in the late second and third trimesters of pregnancy. A fetal echocardiogram should be performed during pregnancy when a couple already has a child with asplenia. Additionally, a level II ultrasound examination can detect some digestive system anomalies, such as the position of the stomach.

Treatment and management

Surgery can sometimes be performed on the heart to repair the defect or defects. There are limitations to heart surgery and it cannot always be performed. Additionally,

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heart surgery is not always successful. Surgery can also be used to correct many of the digestive tract disorders.

Additionally, because the spleen is involved in the body’s immune system, it is recommended that all patients with the diagnosis of asplenia be given antibiotics and pneumococcal vaccination.

Prognosis

Without treatment, the prognosis of an infant diagnosed with asplenia is poor, with approximately 80% of these infants dying within the first year of life. The cause of death is usually complications from the heart defect. However, with advances in heart surgery and improvements in correcting many of the digestive tract anomalies, infants with asplenia are living much longer.

Resources

PERIODICALS

Applegate, K., et. al. “Situs Revisited: Imaging of the Heterotaxy Syndrome.” RadioGraphics 19 (1999): 83752.

Nakada, K., et. al. “Digestive Tract Disorders Associated with Asplenia/Polysplenia Syndrome.” Journal of Pediatric Surgery 32 (1997): 91-94.

Splitt, M. P., et. al. “Defects in the Determination of Left-Right Asymmetry.” Journal of Medical Genetics 33 (1996): 498503.

ORGANIZATIONS

Ivemark Syndrome Association. 52 Keward Ave., Wells,

Somerset, BAS-1TS. UK 1-(74)967-2603.

WEBSITES

Gee, Henry. “The Sources of Symmetry.” Nature: Science Update. (1998) http://www.nature.com.nsu/980806/ 980806-7.html .

“OMIM# 208530: Asplenia with Cardiovascular Anomalies.”

OMIM—Online Mendelian Inheritance in Man.

http://www.ncbi.nih.gov/htbin-post/Omim/ dispmim?208530 . (May 14 1999).

Sharon A. Aufox, MS, CGC

Asplenia/polysplenia complex see Asplenia

I Asthma

Definition

Asthma is a disease of the respiratory system that causes breathing difficulty. Asthma is typically expressed

by repeated but reversible episodes of constriction and inflammation of the airways and lungs. Typical symptoms include wheezing, coughing, and shortness of breath. Technically, asthma is described as a chronic inflammatory disorder of the respiratory system. Asthma has both a genetic and environmental basis. The symptoms of asthma are caused by allergic-like reactions of the body’s immune system to environmental and behavioral stimuli.

Description

Asthma is a chronic, life-long disease that affects the complex network of air passageways of the human respiratory system—the bronchial tubes (airways) and the lungs. Its symptoms range from mild discomfort to life threatening attacks that require immediate emergency treatment. Asthmatic patients can experience “asthma attacks” of varying degrees of severity. These episodes reduce the amount of air that can get in and out of the lungs. Severe asthma attacks can leave individuals gasping for air.

An asthma attack involves the constriction (narrowing) and swelling (inflammation) of the airways (bronchi and bronchioles) and inflammation of the lining of the lungs. As the lining of the airways become inflamed, more mucus is produced. The extra fluid in the mucus is the body’s way of removing foreign substances, such as allergens, that come into contact with body tissues. In medical terms, the narrowing or constriction of the airways is referred to as an “obstruction.” Persistent or chronic inflammation of the airways can cause permanent damage and reduce lung function so that breathing becomes less efficient.

Typical symptoms of asthma include wheezing, coughing, shortness of breath, and tightening of the chest. It is a life-long, chronic condition. Currently, there is no “cure” for asthma, but new, more effective medications and careful management of the disease can help asthmatic patients maintain a quality, active lifestyle.

Chronic asthma is the result of an interaction between heredity and environment. Research has confirmed that some people inherit a strong genetic disposition for asthma that can be “triggered” by a variety of possible environmental factors, such as repeated exposure to irritants such as dust mites, pet hairs, and tobacco smoke.

Modern medical treatment focuses on helping asthma patients achieve control over their own asthma situation on a day to day basis. Another important goal is

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reducing the incidence of severe attacks in patients with the most serious or advanced stages of this disease.

One of the most troubling aspects about asthma is that, despite recent advances in basic research and clinical treatment, scientists have not yet unraveled the complex physiological mechanisms and processes that cause the disease condition referred to as asthma. Also, it is often not possible to pinpoint the exact nature of the triggers that initiate asthmatic symptoms in specific individuals.

There is still no “cure” for asthma, but ongoing medical research has led to improved treatment and management that has dramatically improved the quality of life for people who have asthma. An improvement in environmental conditions in which asthmatics live can reduce the number and severity of asthma attacks and may actually decrease the number of people sensitized to environmental triggers.

In the long term, scientists hope to discover ways to prevent the development of asthma in individuals who have a genetic predisposition for this disease. The medical term for this approach is “primary prevention intervention.”

Unfortunately, the number of asthma cases around the world is increasing at an alarming rate—so fast, in fact, that leading medical authorities now refer to this disease as the “asthma epidemic.” At the beginning of the new millennium, more people in the United States die of chronic diseases, such as asthma, than the ancient scourge of infectious diseases, such as tuberculosis and influenza.

In normal breathing, air enters the nose or mouth, travels down the trachea (windpipe) in the throat and then is carried through a branching network of tubes—the bronchi—to each part of the lungs. These airways end in the alveoli (tiny air sacs) that make up the sponge-like tissues of the lungs. Oxygen and carbon dioxide are exchanged with the blood circulating within the blood vessels surrounding the air sacs. Under the microscope, these air spaces give the human lung tissue a somewhat sponge-like appearance. Asthma attacks not only the bronchial tubes leading to the lungs, but also the entire network of air passageways within the lungs, including the alveoli. Over time, repeated asthmatic episodes cause permanent changes that decrease the size of the airways. The medical term for this change is the “remodeling” of the airways.

Genetic profile

Current medical research continues to refine our understanding of how genes influence the development

and severity of asthma symptoms in individual patients. It has been clearly established that asthma tends to run in families. Recent research, including studies that trace the appearance of asthma in families with twins, suggests that one’s genetic makeup rather than environment is the major factor in determining an individual’s predisposi- tion—or potential—for developing asthma. Studies show that identical twins are more likely to share a genetic predisposition for asthma than are fraternal (non-identical) twins. Still, it is the presence of allergens and other substances in the environment that actually stimulate or “turn on” the genes that are related to asthma.

Determining the role of inheritance in asthma is made more difficult because many different genes seem to be involved in controlling the development and expression of asthma. Thus, there is no clear Mendelian pattern of inheritance of asthma such as in sickle cell anemia disease, which is clearly controlled by the presence or absence of a single gene for that disease.

Some scientists suspect that as many as 20 or more different genes may control an individual’s potential for developing asthma. Scientists refer to this multi-gene component as polygenic heritability. Children of asthmatic parents have about a 30% chance of developing chronic asthma.

The task of identifying the specific genes responsible for various asthma symptoms will be made easier by the Human Genome Project. This mammoth research project has identified all of the genes that make up the 23 pairs of chromosomes in human cells. Much work remains in learning the role of each of these genes in the human body.

Asthma and the immune system

Research studies show that specific symptoms experienced by asthma patients, such as the inflammation of the airways and lungs, are initiated by the action of genes that regulate the activity of the human immune system. In other words, these genes control how the immune system responds to the presence of substances that can potentially trigger asthma symptoms.

Like a modern army, the human immune system consists of a wide array of specialized devices that work together to “neutralize enemy forces.” In human terms, the “enemy forces” are antigens, the term given to any foreign agent invading the body. Antigens include disease producing organisms and toxic chemicals in the environment. The human equivalent of “specialized devices” is a complex network of cells in the immune system. Some of these cells produce antibodies, large molecules made up of proteins, that attack specific types of antigens.

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K E Y T E R M S

Allele—One of two or more alternate forms of a gene.

Allergen—A substance or organism foreign to the body. Allergens stimulate the immune system to produce antibodies.

Allergic rhinitis—Hay fever.

Allergy—Condition in which the immune system is hypersensitive to contact with allergens; an abnormal response by the immune system to contact with an allergen. This condition produces symptoms such as inflammation of tissues and production of excess mucus in respiratory system.

Antibody—A protein produced by the mature B cells of the immune system that attach to invading microorganisms and target them for destruction by other immune system cells.

Antigen—A substance or organism that is foreign to the body and stimulates a response from the immune system.

Atopic—A condition or disease that is the result of an allergic reaction.

Atopic asthma—Asthma caused by an allergic reaction; atopic asthma tends to have a strong inherited component (tends to run in families).

Atopic rhinitis—Also referred to as “hay fever”; symptoms of rhinitis caused by an allergic response to the presence of an allergen (such as tree or grass pollen).

Bronchi—Branching tube-like structures that carry air in and out of the lungs; walls of bronchi contain circular muscles that can constrict (tighten up to make airways narrower) or dilate (relax to make airways wider); bronchi divide into smaller bronchioles within the lung tissue.

Gene—A building block of inheritance, which contains the instructions for the production of a particular protein, and is made up of a molecular sequence found on a section of DNA. Each gene is found on a precise location on a chromosome.

Genetic disease—A disease that is (partly or completely) the result of the abnormal function or expression of a gene; a disease caused by the inheritance and expression of a genetic mutation.

Histamine—A substance released by immune system cells in response to the presence of an allergen; stimulates widening of blood vessels and increased porousness of blood vessel walls so that fluid and protein leaks out from blood to surrounding tissue, causing inflammation of local tissues.

Hypersensitive—A process or reaction that occurs at above normal levels; overreaction to a stimulus.

IgE—An antibody composed of protein; specific forms of IgE produced by cells of immune system in response to different antigens that contact the body; major factor that stimulates the allergic response.

Immune system—A major system of the body that produces specialized cells and substances that interact with and destroy foreign antigens that invade the body.A major system of the body that produces specialized cells and substances that interact with and destroy foreign antigens that invade the body.

Inflammation—Swelling and reddening of tissue; usually caused by the immune system’s response to the body’s contact with an allergen.

Mutation—A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring.

Protein—Important building blocks of the body, composed of amino acids, involved in the formation of body structures and controlling the basic functions of the human body.

Recessive gene—A type of gene that is not expressed as a trait unless inherited by both parents.

Rhinitis—Infection of the nasal passages.

Sensitization—Change in immune system so that it identifies and “remembers” specific properties of an antigen.

The immune system “remembers” its contact with specific antigens, such as viruses, bacteria, and other pathogenic organisms, house dust mites, and plant pollen. Any subsequent—or future—encounter with a “known” antigen stimulates the immune system to produce antibodies that specifically target that antigen.

IgE antibodies

In more detail, scientists have identified a specific set of genes (on the long arm of Chromosome 5, to be exact) that force the immune system to make above normal amounts of the allergic antibody called Immunoglobulin E (IgE) in asthmatic patients. IgE is an

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