What Is Asperger Syndrome?

Asperger syndrome is an autism spectrum disorder (ASD) considered to be on the high functioning end of the spectrum. Affected children and adults have difficulty with social interactions and exhibit a restricted range of interests and/or repetitive behaviors. Motor development may be delayed, leading to clumsiness or uncoordinated motor movements. Compared with those affected by other forms of ASD, however, those with Asperger syndrome do not have significant delays or difficulties in language or cognitive development. Some even demonstrate precocious vocabulary often in a highly specialized field of interest. The following behaviors are often associated with Asperger syndrome. However, they are seldom all present in any one individual and vary widely in degree: limited or inappropriate social interactions "robotic" or repetitive speech challenges with nonverbal communication (gestures, facial expression, etc.) coupled with average to above average verbal skills tendency to discuss self rather than others inability to understand social/emotional issues or nonliteral phrases lack of eye contact or reciprocal conversation obsession with specific, often unusual, topics one-sided conversations awkward movements and/or mannerisms How is Asperger Syndrome diagnosed? Asperger syndrome often remains undiagnosed until a child or adult begins to have serious difficulties in school, the workplace or their personal lives. Indeed, many adults with Asperger syndrome receive their diagnosis when seeking help for related issues such as anxiety or depression. Diagnosis tends to center primarily on difficulties with social interactions. Children with Asperger syndrome tend to show typical or even exceptional language development. However, many tend to use their language skills inappropriately or awkwardly in conversations or social situations such as interacting with their peers. Often, the symptoms of Asperger syndrome are confused with those of other behavioral issues such as attention deficit and hyperactivity disorder (ADHD). Indeed, many persons affected by Asperger syndrome are initially diagnosed with ADHD until it becomes clear that their difficulties stem more from an inability to socialize than an inability to focus their attention. For instance, someone with Asperger syndrome might initiate conversations with others by extensively relating facts related to a particular topic of interest. He or she may resist discussing anything else and have difficulty allowing others to speak. Often, they dont notice that others are no longer listening or are uncomfortable with the topic. They may lack the ability to see things from the other persons perspective. Another common symptom is an inability to understand the intent behind another persons actions, words and behaviors. So children and adults affected by Asperger syndrome may miss humor and

other implications. Similarly, they may not instinctually respond to such universal nonverbal cues such as a smile, frown or come here motion. For these reasons, social interactions can seem confusing and overwhelming to individuals with Asperger syndrome. Difficulties in seeing things from another person's perspective can make it extremely difficult to predict or understand the actions of others. They may not pick up on what is or isnt appropriate in a particular situation. For instance, someone with Asperger syndrome might speak too loudly when entering a church service or a room with a sleeping baby and not understand when shushed. Some individuals with Asperger syndrome have a peculiar manner of speaking. This can involve speaking overly loud, in a monotone or with an unusual intonation. It is also common, but not universal, for people with Asperger syndrome to have difficulty controlling their emotions. They may cry or laugh easily or at inappropriate times. Another common, but not universal, sign is an awkwardness or delay in motor skills. As children, in particular, they may have difficulties on the playground because they cant catch a ball or understand how to swing on the monkey bars despite their peers repeated attempts to teach them. Not all individuals with Asperger syndrome display all of these behaviors. In addition, each of these symptoms tends to vary widely among affected individuals. It is very important to note that the challenges presented by Asperger Syndrome are very often accompanied by unique gifts. Indeed, a remarkable ability for intense focus is a common trait. What kinds of services and supports are there for individuals affected by Asperger Syndrome? There is no single or best treatment for Asperger syndrome. Many adults diagnosed with Asperger syndrome find cognitive behavioral therapy particularly helpful in learning social skills and selfcontrol of emotions, obsessions and repetitive behaviors. Educational and social support programs for children with Asperger syndrome generally teach social and adaptive skills step by step using highly structured activities. The instructor may repeat important ideas or instructions to help reinforce more adaptive behaviors. Many of these programs also involve parent training so that lessons can be continued in the home. Like adults, many children find cognitive behavioral therapy helpful. Group programs can be particularly helpful for social skills training. Speech and language therapy either in a group or one on one with a therapist can likewise help with conversation skills. Many children with Asperger syndrome also benefit from occupational and physical therapy. Most experts feel that the earlier interventions are started, the better the outcome. However, many persons who receive their diagnosis as adults make great strides by coupling their new awareness with counseling. In addition to behavioral interventions, some persons affected by Asperger syndrome are helped by medications such as selective serotonin reuptake inhibitors (SSRIs), antipsychotics and stimulants to treat associated problems such as anxiety, depression and hyperactivity and ADHD.

With increased self-awareness and therapy, many children and adults learn to cope with the challenges of Asperger syndrome. Social interaction and personal relationships may remain difficult. However, many affected adults work successfully in mainstream jobs, and some make great contributions to society. How has our understanding of Asperger Syndrome evolved? In 1944, an Austrian pediatrician named Hans Asperger described four young patients with similar social difficulties. Although their intelligence appeared normal, the children lacked nonverbal communication skills and failed to demonstrate empathy with their peers. Their manner of speech was either disjointed or overly formal, and their all-absorbing interests in narrow topics dominated their conversations. The children also shared a tendency to be clumsy. Dr. Asperger's observations, published in German, remained little known until 1981. In that year, the English physician Lorna Wing published a series of case studies of children with similar symptoms. Wing's writings on Asperger syndrome were widely published and popularized. In 1994, Asperger syndrome was added to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4), the American Psychiatric Association's diagnostic reference book. There can be considerable overlap in the diagnostic symptoms of Asperger and that of other forms of ASD among children and adults who have normal intelligence and no significant language delay. So-called high functioning autism and Asperger syndrome share similar challenges and benefit from similar treatment approaches. In recent years, such high profile authors and speakers as John Elder Robison and animal scientist Temple Grandin have shared their stories of life with Asperger syndrome. In doing so, they have helped raise awareness of its associated challenges and special abilities. Asperger Syndrome and Self-Advocacy Many persons affected with Asperger syndrome take pride in their special abilities. Some take offense at the suggestion that their autism needs to be cured. Prominent self-advocates include Michael John Carley, executive director of the Global and Regional Asperger Syndrome Partnership(GRASP) and the Asperger Syndrome Training and Employment Program (ASTEP), and self-described Aspergian John Elder Robison. Mr. Robison eloquently describes his take on the wider autism self-advocacy movement in the following excerpt from an article he wrote in Psychology Today. Autism is a communication disorder, with a broad range of affect. Some people's autism m akes them eccentric and geeky. Other people can't speak at all, as a result of more severe autistic disability. Therefore, in the world of autism, some of the population is capable of what some call self-advocacy while another part is not. It should come as no surprise that those groups would have very different wants and needs. That disunity of need and purpose is a fundamental issue we must address.

At its heart, self-advocacy is nothing more than speaking up to get what you want. Everyone who communicates does this, all the time. We self-advocate when we ask for different courses in college. We self-advocate when we ask for a chair with a lumbar support at work. You may believe your own communication problems will be reduced if the people around you are willing to change their style of engagement to accommodate you, or you may ask that they excuse some of your expressions, which might otherwise be offensive or unacceptable. Those are all examples of what we call self-advocacy, because the speaker is asking for what he thinks he needs to be successful. What is PDD-NOS? - Pervasive Developmental Disorder-Not Otherwise Specified PDD-NOS stands for Pervasive Developmental Disorder-Not Otherwise Specified. Psychologists and psychiatrists sometimes use the term pervasive developmental disorders and autism spectrum disorders (ASD) interchangeably. As such, PDD-NOS became the diagnosis applied to children or adults who are on the autism spectrum but do not fully meet the criteria for another ASD such as autistic disorder (sometimes called classic autism) or Asperger Syndrome. Like all forms of autism, PDD-NOS can occur in conjunction with a wide spectrum of intellectual ability. Its defining features are significant challenges in social and language development. Some developmental health professionals refer to PDD-NOS as subthreshold autism." In other words, its the diagnosis they use for someone who has some but not all charact eristics of autism or who has relatively mild symptoms. For instance, a person may have significant autism symptoms in one core area such as social deficits, but mild or no symptoms in another core area such as restricted, repetitive behaviors. As a diagnosis, PDD-NOS remains relatively new, dating back only 15 years or so. As a result, some physicians and educators may not be familiar with the term or may use it incorrectly. The current Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) spells out the criteria for a diagnosis of PDD-NOS. Unfortunately, this description consists of a single paragraph, which mainly asserts what it is not: "This category should be used when there is severe and pervasive impairment in the development of reciprocal social interaction associated with impairment in either verbal or nonverbal communication skills or with the presence of stereotyped behavior, interests, and activities, but the criteria are not met for a specific Pervasive Developmental Disorder, Schizophrenia, Schizotypal Personality Disorder, or Avoidant Personality Disorder. For example, this category includes atypical autism presentations that do not meet the criteria for Autistic Disorder because of late age at onset, atypical symptomatology, or subthreshold symptomatology, or all of these." More helpful, perhaps, are studies suggesting that persons with PDD-NOS can be placed in one of three very different subgroups: A high-functioning group (around 25 percent) whose symptoms largely overlap with that of Asperger syndrome, but who differ in terms of having a lag in language development and mild cognitive impairment. (Asperger syndrome does not generally involve speech delay or cognitive impairment). A second group (around 25 percent) whose symptoms more closely resemble those of autistic disorder, but do not fully meet all its diagnostic signs and symptoms.

A third group (around 50 percent) who meet all the diagnostic criteria for autistic disorder, but whose stereotypical and repetitive behaviors are noticeably mild. As these findings suggest, individuals with PDD-NOS vary widely in their strengths and challenges. How might a parent or an affected adult recognize PDD-NOS? PDD-NOS is characterized by delays in the development of socialization and communication skills. Parents may notice associated behaviors as early as infancy. These may include delays in using and understanding language, difficulty relating to people, unusual play with toys and other objects, difficulty with changes in routine or surroundings and repetitive body movements or behavior patterns. (Please also see Learn the Signs.) How should PDD-NOS be treated? As with all autism spectrum disorders, early diagnosis and intervention offer the best chance for optimizing outcomes including success in mainstream classrooms and the achievement of independence and a high quality of life in adulthood. However, it is never too late to begin behavioral therapy. As previously mentioned, no two individuals with PDD-NOS are alike. Indeed, they can have completely different strengths and challenges. As a result, treatments and interventions should be highly individualized based on a thorough assessment by a qualified developmental specialist. The evaluation should consider such factors as behavioral history, current symptoms, communication patterns, social competence and neuropsychological functioning. Parents of children diagnosed with PDD-NOS should pursue an Early Intervention Program (EIP) for a young child and an Individual Education Program (IEP) for a school-age child. For more information, see the Autism Speaks 100 Day Kit and IEP Guide. For more information and resources, please see our Video Glossary and FAQs and special sections on Diagnosis, Symptoms, Learn the Signs, Treatment, Your Childs Rights andAsperger Syndrome. We also offer a number of resource-packed tool kits for free download (here and here). They include our 100 Day Kit for families who have a child recently diagnosed with autism. These resources are made possible through the generous support of our families, volunteers and other donors.

Down syndrome (DS), also called Trisomy 21, is a condition in which extra genetic material
causes delays in the way a child develops, both mentally and physically. It affects about 1 in every 800 babies born in the United States. The physical features and medical problems associated with Down syndrome can vary widely from child to child. While some kids with DS need a lot of medical attention, others lead healthy lives. Though Down syndrome can't be prevented, it can be detected before a child is born. The health problems that may go along with DS can be treated, and many resources are available to help kids and their families who are living with the condition. What Causes It? Normally, at the time of conception a baby inherits genetic information from its parents in the form of 46 chromosomes: 23 from the mother and 23 from the father. In most cases of Down syndrome, a child gets an extra chromosome 21 for a total of 47 chromosomes instead of 46. It's this extra genetic material that causes the physical features and developmental delays associated with DS. Although no one knows for sure why DS occurs and there's no way to prevent the chromosomal error that causes it, scientists do know that women age 35 and older have a significantly higher risk of having a child with the condition. At age 30, for example, a woman has about a 1 in 1,000 chance of conceiving a child with DS. Those odds increase to about 1 in 400 by age 35. By 40 the risk rises to about 1 in 100. Kids with Down syndrome tend to share certain physical features such as a flat facial profile, an upward slant to the eyes, small ears, and a protruding tongue. Low muscle tone (called hypotonia) is also characteristic of children with DS, and babies in particular may seem especially "floppy." Though this can and often does improve over time, most children with DS typically reach developmental milestones like sitting up, crawling, and walking later than other kids. At birth, kids with DS are usually of average size, but they tend to grow at a slower rate and remain smaller than their peers. For infants, low muscle tone may contribute to sucking and feeding problems, as well as constipation and other digestive issues. Toddlers and older kids may have delays in speech and self-care skills like feeding, dressing, and toilet teaching. Down syndrome affects kids' ability to learn in different ways, but most have mild to moderate intellectual impairment. Kids with DS can and do learn, and are capable of developing skills throughout their lives. They simply reach goals at a different pace which is why it's important not to compare a child with DS against typically developing siblings or even other children with the condition. Kids with DS have a wide range of abilities, and there's no way to tell at birth what they will be capable of as they grow up. Medical Problems Associated With DS While some kids with DS have no significant health problems, others may experience a host of medical issues that require extra care. For example, almost half of all children born with DS will have a congenital heart defect. Kids with Down syndrome are also at an increased risk of developing pulmonary hypertension, a serious condition that can lead to irreversible damage to the lungs. All infants with Down syndrome should be evaluated by a pediatric cardiologist. Approximately half of all kids with DS also have problems with hearing and vision. Hearing loss can be related to fluid buildup in the inner ear or to structural problems of the ear itself. Vision problems commonly include strabismus (cross-eyed), near- or farsightedness, and an increased risk of cataracts.

Regular evaluations by an otolaryngologist (ear, nose, and throat doctor), audiologist, and an ophthalmologist are necessary to detect and correct any problems before they affect language and learning skills. Other medical conditions that may occur more frequently in kids with DS include thyroid problems, intestinal abnormalities, seizure disorders, respiratory problems, obesity, an increased susceptibility to infection, and a higher risk of childhood leukemia. Upper neck abnormalities are sometimes found and should be evaluated by a doctor (these can be detected by cervical spine Xrays). Fortunately, many of these conditions are treatable.

Fragile X Syndrome
Fragile X syndrome (FXS) is a genetic condition that causes intellectual disability, behavioral and learning challenges and various physical characteristics. Though FXS occurs in both genders, males are more frequently affected than females, and generally with greater severity. FXS is caused by a full mutation of the FMR1 Gene. Features of Fragile X Syndrome in Males The majority of males with fragile X syndrome demonstrate significant intellectual disability (formerly referred to as mental retardation). Disabilities in FXS include a range from moderate learning disabilities to more severe intellectual disabilities. Physical features may include large ears, long face, soft skin and large testicles (called macroorchidism) in post-pubertal males. Connective tissue problems may include ear infections, flat feet, high arched palate, double-jointed fingers and hyper-flexible joints. Behavioral characteristics can include ADD, ADHD, autism and autistic behaviors, social anxiety, hand-biting and/or flapping, poor eye contact, sensory disorders and increased risk for aggression. No one individual will have all the features of FXS, and some features, such as a long face and macroorchidism, are more common after puberty. Features of Fragile X Syndrome in Females The characteristics seen in males can also be seen in females, though females often have milder intellectual disability and a milder presentation of the syndromes behavioral and physical features. About one-third of females with FXS have a significant intellectual disability. Others may have moderate or mild learning disabilities, emotional/mental health issues, general anxiety and/or social anxiety. A small percentage of females who have the full mutation of the FMR1 Gene that causes FXS will have no apparent signs of the conditionintellectual, behavioral or physical. These females are often identified only after another family member has been diagnosed. Moving Forward While individuals with FXS will experience a number of challenges in their lives, given effective interventions and support they can be engaging and productive members of their families, schools, workplaces and communities as highlighted below in these images and in our Faces of Fragile X section. FMR1 Gene

What Is a Gene? A gene is a unit of heredity that is passed down from parent to child. Genes are located on chromosomes that are in all of our cells, including the sperm and egg that make a baby. What Is a Gene Made Of? Genes are made of molecules or chemicals called DNA. The pattern of DNA will determine if the gene is working properly. The DNA has to be in a certain pattern or order, like the numbers in a phone number.

How Does a Gene Work? A gene has different parts that work together like a factory or machine. It has a promoter that turns the gene on, like a light switch. It has sections that are just filler and act as place holders, called introns. The sections that are used to make a protein or do a job are called exons. What Do Genes Do? The job of a gene is to either make a protein, the building blocks of all the structures in the body, or to regulate other proteins in the body. How Does a Gene Make Proteins? The DNA in the gene is a code that is transcribed or talks to another kind of molecule called RNA. This is like one side of Velcro sticking to another that it matches up to. The RNA then translates the DNA to put together the protein. Now that you understand what genes are, lets discuss the Fragile X gene The Fragile X (FMR1) Gene Why Is It Called the FMR1 Gene? Genes are named when they are discovered. Often the name isnt exactly the same as the condition, in case it is later discovered that there is more than one gene involved in the condition. The gene that causes Fragile X is called the FMR1 gene, which stands for fragile X mental retardation gene. Though the term mental retardation has given way in recent years to the more generally accepted term of intellectual disabilities, the scientific name of the gene cant change with the times.

Ideogram of X chromosome Where Is the FMR1 Gene Located? The FMR1 gene is located on the X chromosome. We all have 46 chromosomes in all of our cells, 44 of which are numbered 1-22 in pairs. Then females have two X chromosomes and males have one X and one Y chromosome. Each chromosome has two arms, one called the p arm (the short arm) and one called the q arm (the long arm). There are many genes on each chromosome, like houses on a street. Each gene is given an address, depending on where it lies on the chromosome. The address of the FMR1 gene is Xq27.3 Does Everyone Have an FMR1 Gene? Yes, everyone has an FMR1 gene. When someone states, I have the gene for Fragile X, they really mean they have a gene mutation for Fragile X. Some Fragile X genes are normal and some are not. What Does the FMR1 Gene Do? The FMR1 gene makes a very important protein called FMRP (fragile X mental retardation protein). Though this protein is found in all our cells, it is most abundant in the nerve cells, and particularly in a part of the nerve cell that talks to other nerve cells called dendrites. What Is an FMR1 Gene Mutation? A mutation is any change in a gene. Some mutations dont cause any problems and we dont know about them (unless found in the laboratory). Mutations in the FMR1 gene involve an abnormal expansion of the DNA in the promoter area of the gene. Often a mutation causes decreased or absent protein production. In individuals with a full mutation, their FMR1 gene is shut down and they dont make enough or any FMRP. Are There Different Kinds of FMR1 Mutations?

Yes. An individual can have a normal FMR1 gene, a premutation or a full mutation. There is also another category called an intermediate allele, which is not a true mutation, but an expansion somewhere between the normal FMR1 gene and the premutation. What Is the Difference Between These Mutations?

FMR1 Gene Categories The mutation of the FMR1 gene involves a repeating pattern of DNA called a CGG repeat. DNA is made of molecules that are abbreviated A, C, G and T. A CGG repeat in the FMR1 gene is a pattern of DNA that may repeats itself anywhere from 30 to 1000 times. In the FMR1 gene there is an area of the promoter that is rich in these CGG repeats and is measured when fragile X testing is performed. In this area, there is normally about 30 repeats of CGG. In individuals with the premutation, there are from 55-200 of these repeats. Persons with the full mutation have more than 200 of the CGG repeats. When there is more than 200 CGG repeats, the gene is turned off by a process called Methylation. Methylation happens to other genes too, when they are supposed to be turned off (as in the genes we dont use, like those that make a tail grow!). In Fragile X the methylation turns off the FMR1 gene, so no FMRP is produced. This is what causes Fragile X Syndrome.

What is Angelman syndrome? Angelman syndrome is a complex genetic disorder that primarily affects the nervous system. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy) and a small head size (microcephaly). Delayed development becomes noticeable by the age of 6 to 12 months, and other common signs and symptoms usually appear in early childhood. Children with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Hyperactivity, a short attention span, and a fascination with water are common. Most affected children also have difficulty sleeping and need less sleep than usual. With age, people with Angelman syndrome become less excitable, and the sleeping problems tend to improve. However, affected individuals continue to have intellectual disability, severe speech impairment, and seizures throughout their lives. Adults with Angelman syndrome have distinctive facial features that may be described as "coarse." Other common features include unusually fair skin with light-colored hair and an abnormal side-to-side curvature of the spine (scoliosis). The life expectancy of people with this condition appears to be nearly normal. How common is Angelman syndrome? Angelman syndrome affects an estimated 1 in 12,000 to 20,000 people. What are the genetic changes related to Angelman syndrome? Many of the characteristic features of Angelman syndrome result from the loss of function of a gene calledUBE3A. People normally inherit one copy of the UBE3A gene from each parent. Both copies of this gene are turned on (active) in many of the body's tissues. In certain areas of the brain, however, only the copy inherited from a person's mother (the maternal copy) is active. This parent-specific gene activation is caused by a phenomenon called genomic imprinting. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain. Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene. In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent. This phenomenon is called paternal uniparental disomy. Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate)UBE3A or other genes on the maternal copy of chromosome 15. The causes of Angelman syndrome are unknown in 10 to 15 percent of affected individuals. Changes involving other genes or chromosomes may be responsible for the disorder in these cases. In some people who have Angelman syndrome, the loss of a gene called OCA2 is associated with light-colored hair and fair skin. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Angelman syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.

Read more about the OCA2 and UBE3A genes and chromosome 15. Can Angelman syndrome be inherited? Most cases of Angelman syndrome are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family. Rarely, a genetic change responsible for Angelman syndrome can be inherited. For example, it is possible for a mutation in the UBE3A gene or in the nearby region of DNA that controls gene activation to be passed from one generation to the next.

How are genetic conditions diagnosed?

A doctor may suspect a diagnosis of a genetic condition on the basis of a persons physical characteristics and family history, or on the results of a screening test. Genetic testing is one of several tools that doctors use to diagnose genetic conditions. The approaches to making a genetic diagnosis include:

A physical examination: Certain physical characteristics, such as distinctive facial features, can suggest the diagnosis of a genetic disorder. A geneticist will do a thorough physical examination that may include measurements such as the distance around the head (head circumference), the distance between the eyes, and the length of the arms and legs. Depending on the situation, specialized examinations such as nervous system (neurological) or eye (ophthalmologic) exams may be performed. The doctor may also use imaging studies including x-rays, computerized tomography (CT) scans, or magnetic resonance imaging (MRI) to see structures inside the body. Personal medical history: Information about an individuals health, often going back to birth, can provide clues to a genetic diagnosis. A personal medical history includes past health issues, hospitalizations and surgeries, allergies, medications, and the results of any medical or genetic testing that has already been done. Family medical history: Because genetic conditions often run in families, information about the health of family members can be a critical tool for diagnosing these disorders. A doctor or genetic counselor will ask about health conditions in an individuals parents, siblings, children, and possibly more distant relatives. This information can give clues about the diagnosis and inheritance pattern of a genetic condition in a family. Laboratory tests, including genetic testing: Molecular, chromosomal, and biochemical genetic testing are used to diagnose genetic disorders. Other laboratory tests that measure the levels of certain substances in blood and urine can also help suggest a diagnosis.

Genetic testing is currently available for many genetic conditions. However, some conditions do not have a genetic test; either the genetic cause of the condition is unknown or a test has not yet been developed. In these cases, a combination of the approaches listed above may be used to make a diagnosis. Even when genetic testing is available, the tools listed above are used to narrow down the possibilities (known as a differential diagnosis) and choose the most appropriate genetic tests to pursue. A diagnosis of a genetic disorder can be made anytime during life, from before birth to old age, depending on when the features of the condition appear and the availability of testing. Sometimes, having a diagnosis can guide treatment and management decisions. A genetic diagnosis can also suggest whether other family members may be affected by or at risk of a specific disorder. Even when no treatment is available for a particular condition, having a diagnosis can help people know what to expect and may help them identify useful support and advocacy resources.

For more information about diagnosing genetic conditions:

Genetics Home Reference provides information about genetic testing and the importance of family medical history. Additionally, links to information about the diagnosis of specific genetic

disorders are available in eachcondition summary under the heading Where can I find information about diagnosis or management of...? Genetic Alliance provides an in-depth guide about genetic counseling called Making Sense of YourGenes , which includes information about how genetics professionals diagnose many types of genetic disorders. This article from Nature Education conditions. discusses the diagnosis of several well-known genetic

The Centers for Disease Control and Prevention (CDC) offers a fact sheet about the diagnosis of birthdefects , including information about screening and diagnostic tests. Boston Childrens Hospital provides this brief overview of testing for genetic disorders . The American College of Medical Genetics offers practice guidelines , including diagnostic criteria, for several genetic disorders. These guidelines are designed for geneticists and other healthcare providers. The Agency for Healthcare Research and Qualitys (AHRQ) National Guideline Clearinghouse has compiledscreening, diagnosis, treatment, and management guidelines for many genetic disorders. GeneReviews , a resource from the University of Washington and the National Center for Biotechnology Information (NCBI), provides detailed information about the diagnosis of specific genetic disorders as part of each peer-reviewed disease description.

How are genetic conditions treated or managed?

Many genetic disorders result from gene changes that are present in essentially every cell in the body. As a result, these disorders often affect many body systems, and most cannot be cured. However, approaches may be available to treat or manage some of the associated signs and symptoms. For a group of genetic conditions called inborn errors of metabolism, which result from genetic changes that disrupt the production of specific enzymes, treatments sometimes include dietary changes or replacement of the particular enzyme that is missing. Limiting certain substances in the diet can help prevent the buildup of potentially toxic substances that are normally broken down by the enzyme. In some cases, enzyme replacement therapy can help compensate for the enzyme shortage. These treatments are used to manage existing signs and symptoms and may help prevent future complications. For other genetic conditions, treatment and management strategies are designed to improve particular signs and symptoms associated with the disorder. These approaches vary by disorder and are specific to an individuals health needs. For example, a genetic disorder associated with a heart defect might be treated with surgery to repair the defect or with a heart transplant. Conditions that are characterized by defective blood cell formation, such as sickle cell disease, can sometimes be treated with a bone marrow transplant. Bone marrow transplantation can allow

the formation of normal blood cells and, if done early in life, may help prevent episodes of pain and other future complications. Some genetic changes are associated with an increased risk of future health problems, such as certain forms of cancer. One well-known example is familial breast cancer related to mutations in the BRCA1 and BRCA2genes. Management may include more frequent cancer screening or preventive (prophylactic) surgery to remove the tissues at highest risk of becoming cancerous. Genetic disorders may cause such severe health problems that they are incompatible with life. In the most severe cases, these conditions may cause a miscarriage of an affected embryo or fetus. In other cases, affected infants may be stillborn or die shortly after birth. Although few treatments are available for these severe genetic conditions, health professionals can often provide supportive care, such as pain relief or mechanical breathing assistance, to the affected individual. Most treatment strategies for genetic disorders do not alter the underlying genetic mutation; however, a few disorders have been treated with gene therapy. This experimental technique involves changing a persons genes to prevent or treat a disease. Gene therapy, along with many other treatment and management approaches for genetic conditions, are under study in clinical trials.

Find out more about the treatment and management of genetic conditions:
Links to information about the treatment of specific genetic disorders are available in each Genetics Home Reference condition summary under the heading Where can I find information about diagnosis or management of...? GeneReviews , a resource from the University of Washington and the National Center for Biotechnology Information (NCBI), provides detailed information about the management of specific genetic disorders as part of each peer-reviewed disease description. The Agency for Healthcare Research and Qualitys (AHRQ) National Guideline Cleari nghouse has compiledscreening, diagnosis, treatment, and management guidelines for many genetic disorders. Information related to the approaches discussed above is available from MedlinePlus:

Inborn Errors of Metabolism Bone Marrow Transplantation Palliative care (also known as supportive care)

Genetics Home Reference offers consumer-friendly information about gene therapy, including safety, ethical issues, and availability. ClinicalTrials.gov , a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for specific trials or browse by condition ,trial sponsor , location , or treatment approach (for example, drug interventions ).

What is genetic testing?

Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a persons chance of developing or passing on a genetic disorder. More than 1,000 genetic tests are currently in use, and more are being developed. Several methods can be used for genetic testing:

Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder. Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition. Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.

Genetic testing is voluntary. Because testing has benefits as well as limitations and risks, the decision about whether to be tested is a personal and complex one. A geneticist or genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing. For general information about genetic testing: MedlinePlus offers a list of links to information about genetic testing . The National Human Genome Research Institute provides an overview of this topic in its Frequently Asked Questions About Genetic Testing . Additional information about genetic testing legislation, policy, andoversight is available from the Institute. The National Institutes of Health fact sheets Genetic Testing: What It Means for Your Health and for Your Familys Health and Genetic Testing: How it is Used for Healthcare each provide a brief overview for people considering genetic testing. Educational resources related to genetic testing are available from GeneEd. The Genetics and Public Policy Center also offers information about genetic testing . You can also search for clinical trials involving genetic testing. ClinicalTrials.gov , a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for specific trials or browse by condition or trial sponsor. You may wish to refer to a list of studies related to genetic testing that are accepting (or will accept) participants.
What are the types of genetic tests?

Genetic testing can provide information about a persons genes and chromosomes. Available types of testing include: Newborn screening

Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants forphenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders. Diagnostic testing Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a persons life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a persons choices about health care and the management of the disorder. Carrier testing Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couples risk of having a child with a genetic condition. Prenatal testing Prenatal testing is used to detect changes in a fetuss genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couples uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however. Preimplantation testing Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a womans ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy. Predictive and presymptomatic testing Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify

mutations that increase a persons risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a persons risk of developing a specific disorder and help with making decisions about medical care. Forensic testing Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity). For more information about the uses of genetic testing: A Brief Primer on Genetic Testing , which outlines the different kinds of genetic tests, is available from the National Human Genome Research Institute. Educational resources related to patient genetic testing/carrier screening GeneEd. are available from

The Centre for Genetics Education offers fact sheets about types of testing used for prenatal diagnosis ,preimplantation genetic diagnosis , and the medical applications of genetic testing and screening . EuroGentest provides fact sheets about predictive testing and carrier testing . The National Newborn Screening and Genetics Resource Center offers detailed information about newborn screening. Additional information about newborn screening , particularly in Australia, is available from the Centre for Genetics Education. For information about forensic DNA testing, refer to the fact sheet DNA Forensics from the U.S. Department of Energy Office of Science and the fact sheet about forensic genetic testing from the Centre for Genetics Education.
How is genetic testing done?

Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a persons doctor or genetic counselor.

Newborn screening tests are done on a small blood sample, which is taken by pricking the babys heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent. For more information about genetic testing procedures: Scientific Testimony, an online journal, provides an introduction to DNA testing techniques written for the general public.
What is direct-to-consumer genetic testing?

Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-toconsumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as athome genetic testing, provides access to a persons genetic information without necessarily involving a doctor or insurance company in the process. If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctors office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion of genetic privacy if testing companies use their genetic information in an unauthorized way. Genetic testing provides only one piece of information about a persons healthother genetic and environmental factors, lifestyle choices, and family medical history also affect a persons risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by at-home genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing.

For more information about direct-to-consumer genetic testing: The American College of Medical Genetics, which is a national association of doctors specializing in genetics, has issued a statement on direct-to-consumer genetic testing . The American Society of Human Genetics, a professional membership organization for specialists in genetics, has also issued a statement on direct-to-consumer genetic testing in the United States . The Federal Trade Commission (FTC) works to protect consumers and promote truth in advertising. The FTC offers a fact sheet for consumers about the benefits and risks of at-home genetic tests. An issue brief on direct-to-consumer genetic testing Policy Center. is available from the Genetics & Public

The Genetic Alliance also provides information about the promotion of genetic testing services directly toconsumers . Additional information about direct-to-consumer marketing of genetic tests the National Human Genome Research Institute. is available from

EuroGentest offers a list of publications related to direct-to-consumer genetic testing in Europe .

How can consumers be sure a genetic test is valid and useful?

Before undergoing genetic testing, it is important to be sure that the test is valid and useful. A genetic test is valid if it provides an accurate result. Two main measures of accuracy apply to genetic tests: analytical validity and clinical validity. Another measure of the quality of a genetic test is its usefulness, or clinical utility.

Analytical validity refers to how well the test predicts the presence or absence of a particular gene or genetic change. In other words, can the test accurately detect whether a specific genetic variant is present or absent? Clinical validity refers to how well the genetic variant being analyzed is related to the presence, absence, or risk of a specific disease. Clinical utility refers to whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer.

All laboratories that perform health-related testing, including genetic testing, are subject to federal regulatory standards called the Clinical Laboratory Improvement Amendments (CLIA) or even stricter state requirements. CLIA standards cover how tests are performed, the qualifications of laboratory personnel, and quality control and testing procedures for each laboratory. By controlling the quality of laboratory practices, CLIA standards are designed to ensure the analytical validity of genetic tests. CLIA standards do not address the clinical validity or clinical utility of genetic tests. The Food and Drug Administration (FDA) requires information about clinical validity for some genetic tests. Additionally, the state of New York requires information on clinical validity for all

laboratory tests performed for people living in that state. Consumers, health providers, and health insurance companies are often the ones who determine the clinical utility of a genetic test. It can be difficult to determine the quality of a genetic test sold directly to the public. Some providers of direct-to-consumer genetic tests are not CLIA-certified, so it can be difficult to tell whether their tests are valid. If providers of direct-to-consumer genetic tests offer easy-tounderstand information about the scientific basis of their tests, it can help consumers make more informed decisions. It may also be helpful to discuss any concerns with a health professional before ordering a direct-to-consumer genetic test. For more information about determining the quality of genetic tests: The Centers for Disease Control and Prevention (CDC) provides an explanation of the factors used to evaluate genetic tests , including analytical validity, clinical validity, and clinical utility, as part of their ACCE project.Additional information about the ACCE framework is available in an interactive tutorial from the PHG Foundation. A brief overview of the regulation of genetic testing Policy Center. is available from the Genetics & Public

The Genetic Alliance offers information about the quality of genetic tests and current public policy issues surrounding their regulation. An interactive tutorial about clinical utility is available from the PHG Foundation. The U.S. Centers for Medicare and Medicaid Services (CMS) provide an overview of the Clinical Laboratory Improvement Amendments (CLIA) . Additional information about the oversight of genetic testing in the United States is available from a Report of the Secretarys Advisory Committee on Genetics, Health, and Society (SACGHS) .
What do the results of genetic tests mean?

The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person s medical history, family history, and the type of genetic test that was done. A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.

A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result. In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result. For more information about interpreting genetic test results: The National Cancer Institute fact sheet Genetic Testing for Hereditary Cancer Syndromes provides an explanation of positive and negative genetic test results. (Scroll down to question 6, What do the results of genetic testing mean?) The Department of Energy, Office of Science offers information about evaluating gene tests . The National Womens Health Resource Center offers a list of questions about genetic testing , including the meaning of test results, that patients and families can ask their healthcare professional.

What is genetic ancestry testing?

Genetic ancestry testing, or genetic genealogy, is a way for people interested in family history (genealogy) to go beyond what they can learn from relatives or from historical documentation. Examination of DNA variations can provide clues about where a per sons ancestors might have come from and about relationships between families. Certain patterns of genetic variation are often shared among people of particular backgrounds. The more closely related two individuals, families, or populations are, the more patterns of variation they typically share. Three types of genetic ancestry testing are commonly used for genealogy:

Y chromosome testing: Variations in the Y chromosome, passed exclusively from father to son, can be used to explore ancestry in the direct male line. Y chromosome testing can only be done on males, because females do not have a Y chromosome. However, women interested in this type of genetic testing sometimes recruit a male relative to have the test done. Because the Y chromosome is passed on in the same pattern as are family names in many cultures, Y chromosome testing is often used to investigate questions such as whether two families with the same surname are related.

Mitochondrial DNA testing: This type of testing identifies genetic variations in mitochondrial DNA. Although most DNA is packaged in chromosomes within the cell nucleus, cell structures called mitochondria also have a small amount of their own DNA (known as mitochondrial DNA). Both males and females have mitochondrial DNA, which is passed on from their mothers, so this type of testing can be used by either sex. It provides information about the direct female ancestral line. Mitochondrial DNA testing can be useful for genealogy because it preserves information about female ancestors that may be lost from the historical record because of the way surnames are often passed down. Single nucleotide polymorphism testing: These tests evaluate large numbers of variations (single nucleotide polymorphisms or SNPs) across a persons entire genome. The results are compared with those of others who have taken the tests to provide an estimate of a persons ethnic background. For example, the pattern of SNPs might indicate that a persons ancestry is approximately 50 percent African, 25 percent European, 20 percent Asian, and 5 percent unknown. Genealogists use this type of test because Y chromosome and mitochondrial DNA test results, which represent only single ancestral lines, do not capture the overall ethnic background of an individual.

Genetic ancestry testing has a number of limitations. Test providers compare individuals t est results to different databases of previous tests, so ethnicity estimates may not be consistent from one provider to another. Also, because most human populations have migrated many times throughout their history and mixed with nearby groups, ethnicity estimates based on genetic testing may differ from an individuals expectations. In ethnic groups with a smaller range of genetic variation due to the groups size and history, most members share many SNPs, and it may be difficult to distinguish people who have a relatively recent common ancestor, such as fourth cousins, from the group as a whole. Genetic ancestry testing is offered by several companies and organizations. Most companies provide online forums and other services to allow people who have been tested to share and discuss their results with others, which may allow them to discover previously unknown relationships. On a larger scale, combined genetic ancestry test results from many people can be used by scientists to explore the history of populations as they arose, migrated, and mixed with other groups.