The Gale Genetic Disorders of encyclopedia vol 2 - part 6 pot

Resources ORGANIZATIONS MAGIC Foundation for Children’s Growth. 1327 N. Harlem Ave., Oak Park, IL 60302. (708) 383-0808 or (800) 362- 4423. Fax: (708) 383-0899. mary@magicfoundation.org. Ͻhttp://www.magicfoundation.org/ghd.htmlϾ. Yahoo Groups: Russell-Silver syndrome Support Group. Ͻhttp://groups.yahoo.com/group/RSS-SupportϾ. WEBSITES Parker, Brandon. “Russell-Silver Syndrome.” Ͻhttp://www .people.unt.edu/~bsp0002/rss.htmϾ. (February 28, 2001). “Russell-Silver Syndrome.” Online Mendelian Inheritance in Man. Ͻhttp://www.ncbi.nlm.nih.gov/entrez/dispomim .cgi?id=180860Ͼ. “Russell-Silver Syndrome.” WebMD. Ͻhttp://my.webmd.com/ content/asset/adam_disease_silver_syndromeϾ. Paul A. Johnson GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1017 Russell-Silver syndrome I Saethre-Chotzen syndrome Definition Saethre-Chotzen syndrome is an inherited disorder that affects one in every 50,000 individuals. The syn- drome is characterized by early and uneven fusion of the bones that make the skull (cranium). This affects the shape of the head and face, which may cause the two sides to appear unequal. The eyelids are droopy; the eyes widely spaced. The disorder is also associated with minor birth defects of the hands and feet. In addition, some indi- viduals have mild mental retardation. Some individuals with Saethre-Chotzen syndrome may require some med- ical or surgical intervention. Description Saethre-Chotzen (say-thre chote-zen) syndrome belongs to a group of rare genetic disorders with cran- iosynostosis. Craniosynostosis means there is premature closure of the sutures (seams) between certain bones of the cranium. This causes the shape of the head to be tall, asymmetric, or otherwise altered in shape (acrocephaly). There is also webbing (syndactyly) of certain fingers and toes. Another name for Saethre-Chotzen syndrome is acrocephalosyndactyly type III. It is one of the more mild craniosynostosis syndromes. The story of Saethre-Chotzen syndrome goes back to the early 1930s. It was then that a Norwegian psychia- trist, Haakon Saethre wrote about a mother and two daughters in the medical literature. Each had a low frontal hairline; long and uneven facial features; short fingers; and webbing of the second and third fingers, and second, third, and fourth toes. A year later in 1931, F. Chotzen, a German psychiatrist, reported a family with similar features. However, these individuals were also quite short and had additional features of mild mental retardation and hearing loss. Genetic profile Saethre-Chotzen is usually found in several genera- tions of a family. It is an autosomal dominant disorder and can be inherited, and passed on, by men as well as women. Almost all genes come in pairs. One copy of each pair of genes is inherited from the father and the other copy of each pair of genes is inherited from the mother. Therefore, if a parent carries a gene mutation for Saethre-Chotzen, each of his or her children has a 50% chance of inheriting the gene mutation. Each child also has a 50% chance of inheriting the working copy of the gene, in which case they would not have Saethre-Chotzen syndrome. The search for the gene for Saethre-Chotzen syn- drome is an interesting story. The first clue as to the cause of the disorder came in 1986, with the identification of patients who had a chromosome deletion of the short arm of chromosome 7. Linkage studies in the early 1990s nar- rowed the region for this gene to a specific site, at 7p21. Then, in 1996, scientists at Johns Hopkins Children’s Center began to study a gene called TWIST as the candi- date gene for Saethre-Chotzen syndrome. The TWIST gene was suspected because of earlier studies that showed how this gene works in the mouse. The mouse TWIST gene normally works in forming the skeleton and muscle of the head, face, hands, and feet. Mice lacking both copies of the gene die before birth. Many have severe birth defects, including failure of the neural tube to close. They have an abnormal head and limb defects. However, mice with just one non-working copy of the TWIST gene did not die. Closer examination of these mice showed that they had only minor hand, foot and skull defects. The features were similar to those seen in Saethre-Chotzen syndrome. It was also known that the mouse TWIST gene was located on chromosome 12 in mice, a location that corre- sponds to the short arm of chromosome 7 in humans. With this evidence, the researchers went on to map and isolate the human TWIST gene on human chromosome 7. They showed that this gene was in the same location GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1019 S that was missing in some individuals with Saethre- Chotzen. The TWIST gene is a small gene, containing only two exons (coding regions). Upon searching for alterations (mutations) in the TWIST gene, they found five different types of mutations in affected individuals. Since none of these mutations were found in unaffected individuals, this was proof positive that the TWIST gene was the cause of Saethre-Chotzen syndrome. Scientists have also used animal models and the fruit fly Drosophila, to study the function of the TWIST gene. They have found that it takes two TWIST protein mole- cules to combine together, in order to function as a tran- scription factor for DNA. The normal function of the TWIST protein is to bind to the DNA helix at specific places. By doing so, it works to regulate which genes are activated or “turned on”. Most of the mutations identified in the TWIST gene so far seem to interfere with how the protein product binds to DNA. In effect, other genes that would normally be activated during development of the embryo may in fact not be turned on. More recent studies suggest that the TWIST protein may induce the activation of genes in the fibroblast growth factor receptor (FGFR) pathway. Mutations in the FGFR family of genes cause other conditions with craniosynostosis such as Crouzon syndrome. Crouzon syndrome, like Saethre-Chotzen syndrome, is a mild craniosynostosis disorder. There is much overlap in the features of the face and hands in each condition. In fact, some patients initially thought to have Saethre- Chotzen were given a new diagnosis of Crouzon syn- drome after studying both the TWIST and the FGFR genes for mutations. In all, it is thought that the TWIST protein most likely acts to turn on the FGFR genes. These genes, in turn, instruct various cells of the head, face, and limb structures to grow and differentiate. If the TWIST gene or other genes of the FGFR pathway are altered, an individual will have one of the craniosynostosis syn- dromes. Demographics Saetre-Chotzen syndrome affects both males and females equally. It most likely occurs in every racial and ethnic group. Approximately one or two in every 50,000 individuals has Saetre-Chotzen syndrome, making it the most common of the craniosynostosis syndromes. Signs and symptoms The cranium is made up of three main sections. The three sections are the face, the base of the cranium, and the top and sides of the head. Most of the cran- ium assumes its permanent shape before birth. How- ever, the bones that make up the top and side of the head are not fixed in place, and the seams between the bones (cranial sutures) remain open. This allows the top of the head to adjust in shape, as the unborn baby passes through the narrow birth canal during labor. After birth, the cranial sutures will close, most often within the first few years of life. The shape of the cranium is then complete. In Saethre-Chotzen, the shape of the cranium is abnormally formed. The reason is that the coronal suture closes too early, sometimes even before birth. The coro- nal suture separates the two frontal bones (forehead) from the parietal bones (top of the head). If the early clo- sure is unilateral or asymmetric, then the forehead and face will form unevenly, from one side to the other. This also forces the top of the head to become more pointed, almost tower-like. The forehead looks high and wide. The face will appear uneven on each side, especially in the area of the eyes and cheeks. There is also less space for the normal features of the face to develop. For instance, the eye sockets are more 1020 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Saethre-Chotzen syndrome KEY TERMS Acrocephaly—An abnormal cone shape of the head. Chromosome deletion—A missing sequence of DNA or part of a chromosome. Craniosynostosis—Premature, delayed, or other- wise abnormal closure of the sutures of the skull. Cranium—The skeleton of the head, which include all of the bones of the head except the mandible. Exon—The expressed portion of a gene. The exons of genes are those portions that actually chemi- cally code for the protein or polypeptide that the gene is responsible for producing. Linkage—The association between separate DNA sequences (genes) located on the same chromo- some. Syndactyly—Webbing or fusion between the fin- gers or toes. Transcription—The process by which genetic information on a strand of DNA is used to synthe- size a strand of complementary RNA. Transcription factor—A protein that works to acti- vate the transcription of other genes. shallow and the cheekbones are flat. This makes the eyes more prominent, and spaced further apart than normal. Adding to the unevenness of the face is drooping of the upper eyelids, and a slight down slant to the eyes. The nose may look beaked or bent slightly downward at the tip. In some individuals, the ears look small and low-set on the face. The other main feature of the syndrome is minor abnormalities of the hands and feet. Webbing (syn- dactyly) commonly occurs between the second and third fingers and toes. The thumbs are short and flat. The fifth finger may be permanently curved or bent at the tip. Each individual with Saetre-Chotzen is affected somewhat differently. The features are usually quite vari- able even within the same family. Most individuals are mildly affected. Their facial features may be somewhat flat and uneven, but not strikingly so. However, if more than one cranial suture closes too early (and this can hap- pen in some individuals), there is more severe disfigure- ment to their face. In addition to the physical characteristics, individu- als with Saetre-Chotzen may have growth delays, leading to less than average adult height. Most individuals are of normal intelligence, although some may have mild to moderate mental retardation (IQ from 50-70). For the growth and mental delays, it becomes necessary to pro- vide special assistance and anticipatory guidance. Diagnosis For many years, there was widespread discussion among physicians (geneticists) over whether a given patient would have either Saethre-Chotzen or Crouzon syndrome. There may even be confusion with other cran- iosynostosis syndromes or with isolated craniosynosto- sis. However, the availability of direct gene testing now allows for a more definitive diagnosis for these patients. Simply using a blood sample, a direct gene test for muta- tions in the TWIST gene can be done. If an individual also has mental retardation or other significant birth defects, it is suggested that they be screened more fully for deletions of the TWIST gene. Treatment and management Very often, the physical characteristics of Saethre- Chotzen are so mild that no surgical treatment is neces- sary. The facial appearance tends to improve as the child grows. However, sometimes surgery is needed to correct the early fusion of the cranial bones. A specialized cran- iofacial medical team, experienced with these types of patients, should do this surgery. Surgery may also be done to release the webbing of the fingers and toes. Some of the more severely affected individuals with Saethre-Chotzen may experience problems with their vision. There may be less space in the eye socket due to the bone abnormalities of the face. This can lead to dam- age of the nerves of the eye and may require corrective surgery. The tear ducts of the eye can also be missing or abnormal. Re-constructive surgery is sometimes per- formed to correct the drooping of the eyelids or narrow- ing of the nasal passage. Prognosis Most individuals with Saethre-Chotzen syndrome appear to have a normal life span. Resources ORGANIZATIONS Children’s Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. contactcca@ccakids.com. Ͻhttp://www.ccakids.comϾ. FACES: The National Craniofacial Association. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332- 2373. faces@faces-cranio.org. Ͻhttp://www.faces-cranio .orgϾ. Forward Face, Inc. 317 East 34th Street, Room 901, New York, NY 10016. (212) 684-5860, (800) 393-3223. MUMS. National Parent to Parent Organization. 150 Custer Court, Green Bay, WI 54301-1243. (920)336-5333. Ͻhttp://www.netnet.net/mumsϾ. WEBSITES “Entry 101400: Seathre-Chotzen Syndrome.” OMIM—Online Mendelian Inheritance in Man. Ͻhttp://www. ncbi.nlm .nih.gov/entrez/dispomim.cgi?id=101400Ͼ. Kevin M. Sweet, MS, CGC Sanfilippo syndrome (MPS III) see Mucopolysaccharidosis (MPS) Sarcoma-breast-leukemia-adrenal gland (SBLA) syndrome see Li-Fraumeni syndrome SC syndrome see Roberts SC phocomelia Scheie syndrome (MPS I) see Mucopolysaccharidosis (MPS) Schilder disease see Adrenoleukodystrophy (ALD) Schinzel acrocallosal syndrome see Acrocallosal syndrome GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1021 Saethre-Chotzen syndrome I Schinzel-Giedion syndrome Definition Schinzel-Giedion syndrome, or Schinzel-Giedion Midface-Retraction syndrome is a rare malformation syndrome characterized by skeletal anomalies, a coarse face, urogenital defects, and severe mental retardation. Description In affected individuals, the ureter, or tube that carries urine from the kidney into the bladder, is obstructed caus- ing the pelvis and kidney duct to become swollen with excess urine. This is called hydronephrosis. Other features of the syndrome include hypertrichosis or the excessive growth of hair, a flat midface, abnormal brain activity, skeletal abnormalities, and severe mental retardation. Patients show abnormal bone maturation including broad and dense ribs and short arms and legs. Severely delayed mental and motor development is accompanied by seizures and spasticity. Genetic profile Some scientists have suggested that the syndrome is inherited as an autosomal recessive trait because they observed that the syndrome appeared in two sibs of dif- ferent sex, which suggested autosomal-recessive inheri- tance. However, other researchers have hypothesized that Schinzel-Giedion syndrome may be a dominant disorder with gonadal mosaicism in one parent. Gonadal mosaicism can occur when either the testes or ovaries contain some cells with an extra chromosome. Scientists have also postulated that the syndrome may be caused by an unbalanced structural chromosome abnormality. Demographics Schinzel-Giedion syndrome is extremely rare and remains incompletely defined. About 25 to 30 well-doc- umented cases have been reported beginning in 1978. The syndrome was originally observed in a brother, who lived less than 24 hours and a sister who survived for 16 months. Both displayed multiple skull abnormalities and profound midface retraction. They each had congenital heart defects, hydronephrosis, clubfoot, and hypertri- chosis. Eight other cases, all sporadic, including two off- spring of consanguineous parents were subsequently identified that year. Less than 30 cases are described in the medical literature detailing major and minor features of the syndrome. Only one case has been described in Japan. The other described cases have occurred in Western countries. Signs and symptoms Clinical signs include a flat midface, low set ears, a prominent forehead, skull abnormalities including large fontanels or openings, a short broad neck, genital mal- formations, congenital heart defects including atrial sep- tal defect, clubfoot, and growth retardation. Diagnosis The detection of renal defects using prenatal ultra- sound is one of the primary means of diagnosis. Clinical observation of coarse facial features, skeletal anomalies, and MRI studies aid diagnosis after birth. Serial cranial MRI studies that show a progressive neurodegenerative process affecting both gray and white matter typify Schinzel-Giedion syndrome. Clinical signs of abnormal cortical gray matter include seizures, dementia, and blindness in some cases. Abnormalities in the white mat- ter can produce spasticity and hypereflexia. Treatment and management MRI studies indicate the syndrome is a progressive neurodegenerative process and patients have a limited life span. Nursing care and supportive measures are required to keep the patient comfortable. Prognosis Death prior to the second year of life represents the most common outcome. Resources BOOKS Menkes, John H., and Harvey B. Sarnat. Child Neurology. 6th ed. Lippincott Williams and Wilkins, 2000. Volpe, Joseph J. Neurology of the Newborn. 4th ed. Philadelphia: W.B. Saunders Company, 2001. PERIODICALS McPherson, E., et al. “Sacral Tumors in Schinzel-Giedion Syndrome.” (Letter) American Journal of Medical Genetics 79 (1998): 62-63. Schinzel, A., and A. Giedion. “A Syndrome of Severe Midface Retraction, Multiple Skull Anomalies, Clubfeet, and 1022 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Schinzel-Giedion syndrome KEY TERMS Hydronephrosis—Obstruction of the tube that car- ries urine from the kidney into the bladder causing the pelvis and kidney duct to become swollen with excess urine. Cardiac and Renal Malformations in Sibs.” American Journal of Medical Genetics 1 (1978): 361-375. Shah, A.M., et al. “Schinzel-Giedion Syndrome: Evidence for a Neurodegenerative Process.” American Journal of Medical Genetics 82 (1999): 344-347. ORGANIZATIONS 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. Ͻhttp://www .rarediseases.orgϾ. WEBSITES “Entry 269150: Schinzel-Giedion Midface-Retraction Syn- drome.” (Last edited 5-12-99). OMIM—Online Mendelian Inheritance in Man. Ͻhttp://www.ncbi.nlm.nih.gov/ entrez/dispomim.cgi?id=269150Ͼ. Julianne Remington I Schizophrenia Definition Schizophrenia is a psychotic disorder (or a group of disorders) marked by severely impaired thinking, emo- tions, and behaviors. Schizophrenic patients are typically unable to filter sensory stimuli and may have enhanced perceptions of sounds, colors, and other features of their environment. Most schizophrenics, if untreated, gradually withdraw from interactions with other people and lose their ability to take care of personal needs and grooming. Description The course of schizophrenia in adults can be divided into three phases or stages. In the acute phase, the patient has an overt loss of contact with reality (psychotic episode) that requires intervention and treatment. In the second or stabilization phase, the initial psychotic symp- toms have been brought under control but the patient is at risk for relapse if treatment is interrupted. In the third or maintenance phase, the patient is relatively stable and can be kept indefinitely on antipsychotic medications. Even in the maintenance phase, however, relapses are not unusual and patients do not always return to full functioning. The term schizophrenia comes from two Greek words that mean “split mind.” It was observed around 1908, by a Swiss doctor named Eugen Bleuler, to describe the splitting apart of mental functions that he regarded as the central characteristic of schizophrenia. Recently, some psychotherapists have begun to use a classification of schizophrenia based on two main types. People with Type I, or positive schizophrenia, have a rapid (acute) onset of symptoms and tend to respond well to drugs. They also tend to suffer more from the “posi- tive” symptoms, such as delusions and hallucinations. People with Type II, or negative schizophrenia, are usu- ally described as poorly adjusted before their schizophre- nia slowly overtakes them. They have predominantly “negative” symptoms, such as withdrawal from others and a slowing of mental and physical reactions (psy- chomotor retardation). The fourth (1994) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) speci- fies five subtypes of schizophrenia. Paranoid The key feature of this subtype of schizophrenia is the combination of false beliefs (delusions) and hearing voices (auditory hallucinations), with more nearly nor- mal emotions and cognitive functioning (cognitive func- tions include reasoning, judgment, and memory). The delusions of paranoid schizophrenics usually involve thoughts of being persecuted or harmed by others or exaggerated opinions of their own importance, but may also reflect feelings of jealousy or excessive religiosity. The delusions are typically organized into a coherent framework. Paranoid schizophrenics function at a higher level than other subtypes, but are at risk for suicidal or violent behavior under the influence of their delusions. Disorganized Disorganized schizophrenia (formerly called hebe- phrenic schizophrenia) is marked by disorganized speech, thinking, and behavior on the patient’s part, cou- pled with flat or inappropriate emotional responses to a situation (affect). The patient may act silly or withdraw socially to an extreme extent. Most patients in this cate- gory have weak personality structures prior to their initial acute psychotic episode. Catatonic Catatonic schizophrenia is characterized by distur- bances of movement that may include rigidity, stupor, agitation, bizarre posturing, and repetitive imitations of the movements or speech of other people. These patients are at risk for malnutrition, exhaustion, or self-injury. This subtype is presently uncommon in Europe and the United States. Catatonia as a symptom is most commonly associated with mood disorders. Undifferentiated Patients in this category have the characteristic posi- tive and negative symptoms of schizophrenia but do not GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1023 Schizophrenia meet the specific criteria for the paranoid, disorganized, or catatonic subtypes. Residual This category is used for patients who have had at least one acute schizophrenic episode but do not presently have strong positive psychotic symptoms, such as delusions and hallucinations. They may have negative symptoms, such as withdrawal from others, or mild forms of positive symptoms, which indicate that the dis- order has not completely resolved. Genetic profile The risk of schizophrenia among first-degree biolog- ical relatives is ten times greater than that observed in the general population. Furthermore, the presence of the same disorder is higher in monozygotic twins (identical twins) than in dizygotic twins (nonidentical twins). The research concerning adoption studies and identical twins also sup- ports the notion that environmental factors are important, because not all relatives who have the disorder express it. There are several chromosomes and loci (specific areas on chromosomes which contain mutated genes) that have been identified. Research is actively ongoing to elucidate the causes, types, and variations of these mutations. Demographics A number of studies indicate that about one percent of the world’s population is affected by schizophrenia, without regard to race, social class, level of education, or cultural influences (outcome may vary from culture to culture, depending on the familial support of the patient). Most patients are diagnosed in their late teens or early twenties, but the symptoms of schizophrenia can emerge at any age in the life cycle. The male/female ratio in adults is about 1.2:1. Male patients typically have their first acute episode in their early twenties, while female patients are usually closer to age 30 when they are rec- ognized with active symptoms. Schizophrenia is rarely diagnosed in preadolescent children, although patients as young as five or six have been reported. Childhood schizophrenia is at the upper end of the spectrum of severity and shows a greater gen- der disparity. It affects one or two children in every 10,000; the male/female ratio is 2:1. Signs and symptoms Theories of causality One of the reasons for the ongoing difficulty in classi- fying schizophrenic disorders is incomplete understanding of their causes. As of 1998, it is thought that these disorders are the end result of a combination of genetic, neurobio- logical, and environmental causes. A leading neurobiolog- ical hypothesis looks at the connection between the disease and excessive levels of dopamine, a chemical that transmits signals in the brain (neurotransmitter). The genetic factor in schizophrenia has been underscored by recent findings that first-degree biological relatives of schizophrenics are ten times as likely to develop the dis- order as are members of the general population. Prior to recent findings of abnormalities in the brain structure of schizophrenic patients, several generations of psychotherapists advanced a number of psychoanalytic and sociological theories about the origins of schizophre- nia. These theories ranged from hypotheses about the patient’s problems with anxiety or aggression to theories about stress reactions or interactions with disturbed par- ents. Psychosocial factors are now thought to influence the expression or severity of schizophrenia, rather than cause it directly. Another hypothesis suggests that schizophrenia may be caused by a virus that attacks the hippocampus, a part of the brain that processes sense perceptions. Damage to the hippocampus would account for schizophrenic patients’ vulnerability to sensory overload. As of mid- 1998, researchers were preparing to test antiviral med- ications on schizophrenics. Symptoms of schizophrenia Patients with a possible diagnosis of schizophrenia are evaluated on the basis of a set or constellation of symptoms; there is no single symptom that is unique to schizophrenia. In 1959, the German psychiatrist Kurt Schneider proposed a list of so-called first-rank symp- toms, which he regarded as diagnostic of the disorder. These symptoms include: • delusions • somatic hallucinations • hearing voices commenting on the patient’s behavior • thought insertion or thought withdrawal. Somatic hallucinations refer to sensations or percep- tions concerning body organs that have no known med- ical cause or reason, such as the notion that one’s brain is radioactive. Thought insertion and/or withdrawal refers to delusions that an outside force (for example, the FBI, the CIA, Martians, etc.) has the power to put thoughts into one’s mind or remove them. Positive symptoms The positive symptoms of schizophrenia are those that represent an excessive or distorted version of normal 1024 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Schizophrenia functions. Positive symptoms include Schneider’s first- rank symptoms as well as disorganized thought processes (reflected mainly in speech) and disorganized or cata- tonic behavior. Disorganized thought processes are marked by such characteristics as looseness of associa- tions, in which the patient rambles from topic to topic in GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1025 Schizophrenia KEY TERMS Affective flattening—A loss or lack of emotional expressiveness. It is sometimes called blunted or restricted affect. Akathisia—Agitated or restless movement, usually affecting the legs and accompanied by a sense of discomfort. It is a common side effect of neurolep- tic medications. Catatonic behavior—Behavior characterized by muscular tightness or rigidity and lack of response to the environment. In some patients, rigidity alter- nates with excited or hyperactive behavior. Delusion—A fixed, false belief that is resistant to reason or factual disproof. Depot dosage—A form of medication that can be stored in the patient’s body tissues for several days or weeks, thus minimizing the risk of the patient for- getting daily doses. Haloperidol and fluphenazine can be given in depot form. Dopamine receptor antagonists (DAs)—The older class of antipsychotic medications, also called neuro- leptics. These primarily block the site on nerve cells that normally receive the brain chemical dopamine. Dystonia—Painful involuntary muscle cramps or spasms. Extrapyramidal symptoms (EPS)—A group of side effects associated with antipsychotic medications. EPS include parkinsonism, akathisia, dystonia, and tardive dyskinesia. First-rank symptoms—A set of symptoms desig- nated by Kurt Schneider in 1959 as the most impor- tant diagnostic indicators of schizophrenia. These symptoms include delusions, hallucinations, thought insertion or removal, and thought broad- casting. First-rank symptoms are sometimes referred to as Schneiderian symptoms. Hallucination—A sensory experience of something that does not exist outside the mind. A person can experience a hallucination in any of the five senses. Auditory hallucinations are a common symptom of schizophrenia. Huntington’s chorea—A hereditary disease that typically appears in midlife, marked by gradual loss of brain function and voluntary movement. Some of its symptoms resemble those of schizo- phrenia. Negative symptoms—Symptoms of schizophrenia characterized by the absence or elimination of cer- tain behaviors. DSM-IV specifies three negative symptoms: affective flattening, poverty of speech, and loss of will or initiative. Neuroleptic—Another name for the older type of antipsychotic medications given to schizophrenic patients. Parkinsonism—A set of symptoms originally associ- ated with Parkinson disease that can occur as side effects of neuroleptic medications. The symptoms include trembling of the fingers or hands, a shuffling gait, and tight or rigid muscles. Positive symptoms—Symptoms of schizophrenia that are characterized by the production or presence of behaviors that are grossly abnormal or excessive, including hallucinations and thought-process disorder. DSM-IV subdivides positive symptoms into psychotic and disorgan- ized. Poverty of speech—A negative symptom of schizo- phrenia, characterized by brief and empty replies to questions. It should not be confused with shyness or reluctance to talk. Psychotic disorder—A mental disorder character- ized by delusions, hallucinations, or other symp- toms of lack of contact with reality. The schizophrenias are psychotic disorders. Serotonin dopamine antagonist (SDA)—The newer second-generation antipsychotic drugs, also called atypical antipsychotics. SDAs include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). Wilson disease—A rare hereditary disease marked by high levels of copper deposits in the brain and liver. It can cause psychiatric symptoms resembling schizophrenia. Word salad—Speech that is so disorganized that it makes no linguistic or grammatical sense. a disconnected way; tangentially, which means that the patient gives unrelated answers to questions; and “word salad,” in which the patient’s speech is so incoherent that it makes no grammatical or linguistic sense. Disorganized behavior means that the patient has diffi- culty with any type of purposeful or goal-oriented behav- ior, including personal self-care or preparing meals. Other forms of disorganized behavior may include dress- ing in odd or inappropriate ways, sexual self-stimulation in public, or agitated shouting or cursing. Negative symptoms The DSM-IV definition of schizophrenia includes three so-called negative symptoms. They are called neg- ative because they represent the lack or absence of behav- iors. The negative symptoms that are considered diagnostic of schizophrenia are a lack of emotional response (affective flattening), poverty of speech, and absence of volition or will. In general, the negative symp- toms are more difficult for doctors to evaluate than the positive symptoms. Diagnosis A doctor must make a diagnosis of schizophrenia on the basis of a standardized list of outwardly observable symptoms, not on the basis of internal psychological processes. There are no specific laboratory tests that can be used to diagnose schizophrenia. Researchers have, however, discovered that patients with schizophrenia have certain abnormalities in the structure and functioning of the brain compared to normal test subjects. These discov- eries have been made with the help of imaging techniques such as computed tomography scans (CT scans). When a psychiatrist assesses a patient for schizo- phrenia, he or she will begin by excluding physical con- ditions that can cause abnormal thinking and some other behaviors associated with schizophrenia. These condi- tions include organic brain disorders (including traumatic injuries of the brain) temporal lobe epilepsy, Wilson disease, Huntington’s chorea, and encephalitis. The doc- tor will also need to rule out substance abuse disorders, especially amphetamine use. After ruling out organic disorders, the clinician will consider other psychiatric conditions that may include psychotic symptoms or symptoms resembling psychosis. These disorders include mood disorders with psychotic features; delusional disorder; dissociative disorder not otherwise specified (DDNOS) or multiple personality disorder; schizotypal, schizoid, or paranoid personality disorders; and atypical reactive disorders. In the past, many individuals were incorrectly diagnosed as schizo- phrenic. Some patients who were diagnosed prior to the changes in categorization introduced by DSM-IV should have their diagnoses, and treatment, reevaluated. In chil- dren, the doctor must distinguish between psychotic symptoms and a vivid fantasy life, and also identify learning problems or disorders. After other conditions have been ruled out, the patient must meet a set of crite- ria specified by DSM-IV: • Characteristic symptoms. The patient must have two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms. • Decline in social, interpersonal, or occupational func- tioning, including self-care. • Duration. The disturbed behavior must last for at least six months. • Diagnostic exclusions. Mood disorders, substance abuse disorders, medical conditions, and developmental disorders have been ruled out. Treatment and management The treatment of schizophrenia depends in part on the patient’s stage or phase. Patients in the acute phase are hospitalized in most cases, to prevent harm to the patient or others and to begin treatment with antipsy- chotic medications. A patient having a first psychotic episode should be given a CT or MRI (magnetic reso- nance imaging) scan to rule out structural brain disease. Antipsychotic medications The primary form of treatment of schizophrenia is antipsychotic medication. Antipsychotic drugs help to control almost all the positive symptoms of the disorder. They have minimal effects on disorganized behavior and negative symptoms. Between 60-70% of schizophrenics will respond to antipsychotics. In the acute phase of the illness, patients are usually given medications by mouth or by intramuscular injection. After the patient has been stabilized, the antipsychotic drug may be given in a long- acting form called a depot dose. Depot medications last two to four weeks; they have the advantage of protecting the patient against the consequences of forgetting or skipping daily doses. In addition, some patients who do not respond to oral neuroleptics have better results with depot form. Patients whose long-term treatment includes depot medications are introduced to the depot form grad- ually during their stabilization period. Most people with schizophrenia are kept on antipsychotic medications indefinitely during the maintenance phase of their disor- der to minimize the possibility of relapse. As of 1998, the most frequently used antipsychotics fall into two classes: the older dopamine receptor antag- 1026 GALE ENCYCLOPEDIA OF GENETIC DISORDERS Schizophrenia onists, or DAs, and the newer serotonin dopamine antag- onists, or SDAs. (Antagonists block the action of some other substance; for example, dopamine antagonists counteract the action of dopamine.) The exact mecha- nisms of action of these medications are not known, but it is thought that they lower the patient’s sensitivity to sensory stimuli and so indirectly improve the patient’s ability to interact with others. DOPAMINE RECEPTOR ANTAGONIST The dopamine antagonists include the older antipsychotic (also called neuroleptic) drugs, such as haloperidol (Haldol), chlor- promazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks: it is often diffi- cult to find the best dosage level for the individual patient, and a dosage level high enough to control psychotic symptoms frequently produces extrapyramidal side effects, or EPS. EPSs include parkinsonism, in which the patient cannot walk normally and usually develops a tremor; dystonia, or painful muscle spasms of the head, tongue, or neck; and akathisia, or restlessness. A type of long-term EPS is called tardive dyskinesia, which features slow, rhythmic, automatic movements. Schizophrenics with AIDS are especially vulnerable to developing EPS. SERATONIN DOPANINE ANTAGONISTS The sero- tonin dopamine antagonists, also called atypical antipsy- chotics, are newer medications that include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). The SDAs have a better effect on the negative symptoms of schizophrenia than do the older drugs and are less likely to produce EPS than the older compounds. The newer drugs are significantly more expensive in the short term, although the SDAs may reduce long-term costs by reducing the need for hospitalization. They are also presently unavailable in injectable forms. The SDAs are commonly used to treat patients who respond poorly to the DAs. However, many psychotherapists now regard the use of these atypical antipsychotics as the treatment of first choice. Psychotherapy Most schizophrenics can benefit from psychotherapy once their acute symptoms have been brought under con- trol by antipsychotic medication. Psychoanalytic approaches are not recommended. Behavior therapy, however, is often helpful in assisting patients to acquire skills for daily living and social interaction. It can be combined with occupational therapy to prepare the patient for eventual employment. Family therapy Family therapy is often recommended for the fami- lies of schizophrenic patients, to relieve the feelings of guilt that they often have as well as to help them under- stand the patient’s disorder. The family’s attitude and behaviors toward the patient are key factors in minimiz- ing relapses (for example, by reducing stress in the patient’s life), and family therapy can often strengthen the family’s ability to cope with the stresses caused by the schizophrenic’s illness. Family therapy focused on communication skills and problem-solving strategies is particularly helpful. In addition to formal treatment, many families benefit from support groups and similar mutual help organizations for relatives of schizophrenics. Prognosis One important prognostic sign is the patient’s age at onset of psychotic symptoms. Patients with early onset of schizophrenia are more often male, have a lower level of functioning prior to onset, a higher rate of brain abnor- malities, more noticeable negative symptoms, and worse outcomes. Patients with later onset are more likely to be female, with fewer brain abnormalities and thought impairment, and more hopeful prognoses. The average course and outcome for schizophrenics are less favorable than those for most other mental disor- ders, although as many as 30% of patients diagnosed with schizophrenia recover completely and the majority experience some improvement. Two factors that influ- ence outcomes are stressful life events and a hostile or emotionally intense family environment. Schizophrenics with a high number of stressful changes in their lives, or who have frequent contacts with critical or emotionally overinvolved family members, are more likely to relapse. Overall, the most important component of long-term care of schizophrenic patients is complying with their regimen of antipsychotic medications. Resources BOOKS Campbell, Robert Jean. Psychiatric Dictionary. New York and Oxford, UK: Oxford University Press, 1989. Clark, R. Barkley. “Psychosocial Aspects of Pediatrics & Psychiatric Disorders.” In Current Pediatric Diagnosis & Treatment, edited by William W. Hay Jr., et al. Stamford, CT: Appleton & Lange, 1997. Day, Max, and Elvin V. Semrad. “Schizophrenia: Comprehen- sive Psychotherapy.” In The Encyclopedia of Psychiatry, Psychology, and Psychoanalysis, edited by Benjamin B. Wolman. New York: Henry Holt and Company, 1996. Eisendrath, Stuart J. “Psychiatric Disorders.” In Current Medi- cal Diagnosis & Treatment 1998, edited by Lawrence M. Tierney Jr., et al. Stamford, CT: Appleton & Lange, 1997. Marder, Stephen R. “Schizophrenia.” In Conn’s Current Therapy, edited by Robert E. Rakel. Philadelphia: W. B. Saunders Company, 1998. “Psychiatric Disorders: Schizophrenic Disorders.” In The Merck Manual of Diagnosis and Therapy. Vol. I, edited by GALE ENCYCLOPEDIA OF GENETIC DISORDERS 1027 Schizophrenia [...]... Joseph’s Hospital, 7 62 0 York Rd., Towson, MD 21 204 (410) 337 125 0 National Eye Institute 31 Center Drive, Bldg 31, Room6A 32, MSC 25 10, Bethseda, MD 20 8 9 2- 2510 (301) 49 6- 524 8 20 20@nei.nih.gov Ͻhttp://www.nei.nih.govϾ National Organization for Rare Disorders (NORD) PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 (20 3) 74 6- 6 518 or (800) 99 9 -6 67 3 Fax: (20 3) 74 6- 6 481 Ͻhttp://www rarediseases.orgϾ WEBSITES Genetic Alliance... of the Literature.” American Journal of Hematology (April 1999): 6 2- 65 GALE ENCYCLOPEDIA OF GENETIC DISORDERS National Heart, Lung, and Blood Institute PO Box 30105, Bethesda, MD 20 824 -0 105 (301) 5 9 2- 8573 nhlbiinfo @rover.nhlbi.nih.gov Ͻhttp://www.nhlbi.nih.govϾ National Organization for Rare Disorders (NORD) PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 (20 3) 74 6- 6 518 or (800) 99 9 -6 67 3 Fax: (20 3) 74 6- 6 481... South, Suite 150, Atlanta, GA 30 329 (404) 63 3-3 777 Ͻhttp:// www.rheumatology.orgϾ National Organization for Rare Disorders (NORD) PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 (20 3) 74 6- 6 518 or (800) 99 9 -6 67 3 Fax: (20 3) 74 6- 6 481 Ͻhttp://www rarediseases.orgϾ Scleroderma Foundation 12 Kent Way, Suite 101, Byfield, MA 01 922 (978) 46 3-5 843 or (800) 722 -HOPE Fax: (978) 46 3-5 809 Ͻhttp://www.scleroderma.org.Ͼ... extended period of time, although they are often faced with profound mental and physical deficits Resources ORGANIZATIONS Human Growth Foundation 997 Glen Cove Ave., Glen Head, NY 11545 (800) 45 1 -6 434 Fax: (5 16) 67 1-4 055 Ͻhttp://www.hgf1@hgfound.orgϾ National Organization for Rare Disorders (NORD) PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 (20 3) 74 6- 6 518 or (800) 99 9 -6 67 3 Fax: (20 3) 74 6- 6 481 Ͻhttp://www... where the extra fingers/toes are on the same side of the hand/foot as the thumb/big toe Other distinguishing features include cleft lip and palate and liver damage The tibia (one of the bones of the lower leg) is often oval shaped and shorter than the fibula (the other bone of the lower leg) The ends of the bones may also appear smooth on an x ray GALE ENCYCLOPEDIA OF GENETIC DISORDERS Verma-Namauf... Frequent pneumonia (Gale Group) contain 23 pairs of chromosomes for a total of 46 chromosomes One of each pair of chromosomes is inherited from the mother and the other is inherited from the father SCID is usually inherited in one of two ways: X-linked recessive or autosomal recessive Autosomal recessive means that the gene for the disease or trait is located on one of the first 22 pairs of chromosomes,... deformity of the upper part of the thigh bone • a flattened joint socket where the hip and thigh bone meet • specific changes in the development of the bones in the hand • bowing of the long bones, especially the leg bones • curvature of the spine that causes a hunchback appearance Many of the symptoms of SJS are also present in other conditions and it is important to distinguish SJS from the following disorders: ... Most Zealous Foe.” The New York Times Magazine (February 22 , 1998): 26 -2 9 ORGANIZATIONS National Alliance for the Mentally Ill Colonial Place Three, 21 07 Wilson Blvd., Suite 300 Arlington, VA 22 201 (703) 524 -7 60 0 HelpLine: (800) 950-NAMI Ͻhttp://www.nami org/Ͼ Schizophrenics Anonymous 15 920 W Twelve Mile, Southfield, MI 480 76 (24 8) 47 7-1 983 WEBSITES “An Introduction to Schizophrenia.” The Schizophrenia... scleroderma Other tests can be performed to evaluate the extent of the disease These include a test of the electrical system of the heart (an electrocardiogram), lung-function GALE ENCYCLOPEDIA OF GENETIC DISORDERS KEY TERMS Autoimmune disorder—A disorder in which the body’s immune cells mistake the body’s own tissues as foreign invaders; the immune cells then work to destroy tissues in the body Collagen The. .. every cell of their body One of each kind (23 total) is inherited from the mother and another of each kind (23 total) is inherited from the father, for a total of 46 One chromosome may hold hundreds to thousands of individual genes and as the chromosomes exist in pairs, so do the genes Therefore, every person has two copies of the HSPG2 gene that makes perlecan Individuals that have a diagnosis of SJS . Rare Disorders (NORD). PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 . (20 3) 74 6- 6 518 or (800) 99 9 -6 673. Fax: (20 3) 74 6- 6 481. Ͻhttp://www .rarediseases.orgϾ. WEBSITES “Entry 26 9150: Schinzel-Giedion. Rare Disorders (NORD). PO Box 8 923 , New Fairfield, CT 068 1 2- 8 923 . (20 3) 74 6- 6 518 or (800) 99 9 -6 673. Fax: (20 3) 74 6- 6 481. Ͻhttp://www .rarediseases.orgϾ. WEBSITES Genetic Alliance. Ͻhttp://www.geneticalliance.orgϾ. Malignant. Joseph’s Hospital, 7 62 0 York Rd., Towson, MD 21 204. (410) 33 7- 125 0. National Eye Institute. 31 Center Drive, Bldg. 31, Room6A 32, MSC 25 10, Bethseda, MD 20 8 9 2- 2510. (301) 49 6- 524 8. 20 20@nei.nih.gov.