Gale Encyclopedia of Genetic Disorder / Gale Encyclopedia of Genetic Disorders, Two Volume Set - Volume 2 - M-Z - I

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. http://www

.rarediseases.org .

WEBSITES

“Entry 269150: Schinzel-Giedion Midface-Retraction Syndrome.” (Last edited 5-12-99). OMIM—Online Mendelian Inheritance in Man. http://www.ncbi.nlm.nih.gov/ entrez/dispomim.cgi?id=269150 .

Julianne Remington

I Schizophrenia

Definition

Schizophrenia is a psychotic disorder (or a group of disorders) marked by severely impaired thinking, emotions, 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 symptoms 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 “positive” symptoms, such as delusions and hallucinations. People with Type II, or negative schizophrenia, are usually described as poorly adjusted before their schizophrenia slowly overtakes them. They have predominantly “negative” symptoms, such as withdrawal from others and a slowing of mental and physical reactions (psychomotor retardation).

The fourth (1994) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) specifies 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 normal emotions and cognitive functioning (cognitive functions 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 hebephrenic schizophrenia) is marked by disorganized speech, thinking, and behavior on the patient’s part, coupled 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 category have weak personality structures prior to their initial acute psychotic episode.

Catatonic

Catatonic schizophrenia is characterized by disturbances 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 positive and negative symptoms of schizophrenia but do not

Schizophrenia

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 disorder has not completely resolved.

Genetic profile

The risk of schizophrenia among first-degree biological 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 supports 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 recognized 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 gender 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 classifying 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, neurobiological, and environmental causes. A leading neurobiological 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 disorder 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 schizophrenia. These theories ranged from hypotheses about the patient’s problems with anxiety or aggression to theories about stress reactions or interactions with disturbed parents. 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 mid1998, researchers were preparing to test antiviral medications 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 symptoms, 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 perceptions concerning body organs that have no known medical 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

Schizophrenia

Schizophrenia

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 difficulty with any type of purposeful or goal-oriented behavior, including personal self-care or preparing meals. Other forms of disorganized behavior may include dressing 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 negative because they represent the lack or absence of behaviors. 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 symptoms 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 discoveries have been made with the help of imaging techniques such as computed tomography scans (CT scans).

When a psychiatrist assesses a patient for schizophrenia, he or she will begin by excluding physical conditions that can cause abnormal thinking and some other behaviors associated with schizophrenia. These conditions include organic brain disorders (including traumatic injuries of the brain) temporal lobe epilepsy, Wilson disease, Huntington’s chorea, and encephalitis. The doctor 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 schizophrenic. Some patients who were diagnosed prior to the

changes in categorization introduced by DSM-IV should have their diagnoses, and treatment, reevaluated. In children, 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 criteria 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 functioning, 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 antipsychotic medications. A patient having a first psychotic episode should be given a CT or MRI (magnetic resonance 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 longacting 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 gradually during their stabilization period. Most people with schizophrenia are kept on antipsychotic medications indefinitely during the maintenance phase of their disorder to minimize the possibility of relapse.

As of 1998, the most frequently used antipsychotics fall into two classes: the older dopamine receptor antag-

onists, or DAs, and the newer serotonin dopamine antagonists, or SDAs. (Antagonists block the action of some other substance; for example, dopamine antagonists counteract the action of dopamine.) The exact mechanisms 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), chlorpromazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks: it is often difficult 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 serotonin dopamine antagonists, also called atypical antipsychotics, 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 control 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 families 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 minimizing 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 abnormalities, 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 disorders, although as many as 30% of patients diagnosed with schizophrenia recover completely and the majority experience some improvement. Two factors that influence 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: Comprehensive 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 Medical 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

Schizophrenia

Schwartz-Jampel syndrome

Robert Berkow, et al. Rahway, NJ: Merck Research Laboratories, 1992.

“Schizophrenia and Other Psychotic Disorders.” In Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: The American Psychiatric Association, 1994.

Schultz, Clarence G. “Schizophrenia: Psychoanalytic Views.” In The Encyclopedia of Psychiatry, Psychology, and Psychoanalysis, edited by Benjamin B. Wolman. New York: Henry Holt and Company, 1996.

Tsuang, Ming T., et al. “Schizophrenic Disorders.” In The New

Harvard Guide to Psychiatry, edited by Armand M. Nicholi, Jr. Cambridge, MA, and London, UK: The Belknap Press of Harvard University Press, 1988.

Wilson, Billie Ann, et al. Nurses Drug Guide 1995. Norwalk, CT: Appleton & Lange, 1995.

PERIODICALS

Schizophrenia On-line News Articles.

http://www2.addr.com/~y/mn/ .

Winerip, Michael. “Schizophrenia’s Most Zealous Foe.” The

New York Times Magazine (February 22, 1998): 26-29.

ORGANIZATIONS

National Alliance for the Mentally Ill. Colonial Place Three, 2107 Wilson Blvd., Suite 300 Arlington, VA 22201. (703) 524-7600 HelpLine: (800) 950-NAMI. http://www.nami

.org/ .

Schizophrenics Anonymous. 15920 W. Twelve Mile, Southfield, MI 48076. (248) 477-1983.

WEBSITES

“An Introduction to Schizophrenia.” The Schizophrenia Homepage. http://www.schizophrenia.com/family/schizintro

.html .

“Schizophrenia.” Internet Mental Health.

http://www.mentalhealth.com/dis/p20-ps01.html .

Laith Farid Gulli, MD

I Schwartz-Jampel syndrome

Definition

Schwartz-Jampel syndrome (SJS) is a rare, inherited condition of the skeletal and muscle systems that causes short stature, joint limitations, and particular facial features.

Description

First described in 1962, SJS is now a clearly defined syndrome that is divided into two types. Type 1A is the classical form that develops in early childhood, usually between the first and third year of life. Type 1B is less common but more severe and its symptoms are present at birth.

Both types of SJS involve generalized disease of the muscles called myopathy. The muscles tend to be quite stiff and are unable to relax normally. This is a condition known as myotonia. The myotonia causes many joints in the body to stay in a bent or flexed position (joint contractures).

In addition to muscle problems, the bones in the skeleton do not develop normally and this is why SJS may also be called a type of skeletal dysplasia. Abnormal bone shape and poor bone growth result in decreased total height, incorrect arm and leg postures, as well as curving of the spine (scoliosis).

Unique facial features of SJS include narrow eye openings with drooping eye lids, a small mouth, and puckered lips. These features are also due to the stiffness of the muscles that support the face and individuals with SJS appear to have a fixed facial expression.

Persons affected with SJS often have normal intelligence, although varying degrees of mental retardation may affect as many as 25% of patients. However, the myotonia may lead to poor speech articulation and drooling so that affected individuals are sometimes misdiagnosed as having mental retardation.

Respiratory and feeding difficulties are frequent with SJS Type 1B due to the more severe nature of the muscle and bone disease. These problems may be fatal in early infancy. Persons with SJS Type 1A have a much longer life expectancy, although this depends on how their disease progresses.

SJS has also been referred to as:

•myotonic myopathy, dwarfism, chrondrodystrophy, and ocular and facial abnormalities

•Schwartz-Jampel-Aberfeld syndrome

•Schwartz syndrome

•Aberfeld syndrome

•chrondrodystrophic myotonia

•osteochondromuscular dystrophy

•spondylo-epimetaphyseal dysplasia with myotonia

Genetic profile

Both types of SJS are known to be inherited in an autosomal recessive manner. This was concluded after the following observations were made. SJS affects males and females alike. Parents of affected individuals rarely show any signs or symptoms of SJS. Parents have been reported to have more than one affected child. Consanguineous relationships were seen in some families.

Genetic studies of many families revealed that all cases of SJS were linked to an area on chromosome one, described as 1p36.1. A gene in this region, named

HSPG2, makes a protein called perlecan that is thought to play the primary role in causing SJS. The function of the perlecan protein is not completely understood. However, it has an important job in the cells of the body’s connective tissue (bone, cartilage, muscles, ligaments, tendons and blood vessels). As of the year 2001, studies have shown that perlecan helps keep cartilage and bone strong and are essential for certain chemical processes in the muscle tissue. It is also thought that perlecan helps to direct the normal growth of some cells.

The gene for perlecan (HSPG2) is fairly large and mistakes or mutations in the instructions of the gene have been found in some persons with SJS. These gene mutations change how the perlecan protein is made and usually prevents it from doing its normal job in the muscles and bones of the body. The effects of these HSPG2 gene mutations cause SJS.

The location 1p36.1 means that the gene is near the top or end of the short arm of chromosome number one. A human being has 23 pairs of chromosomes in nearly 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 are thought to have a mutation in both copies of their HSPG2 gene, each of which was inherited from one of their parents. Unaffected parents of children with SJS are therefore carriers for SJS. Their one normal HSPG2 gene appears to make enough perlecan so those carriers do not show any symptoms of SJS. Most parents do not know that they are carriers for SJS until they have an affected child. When both parents are carriers for the same autosomal recessive disease such as SJS, there is a 25% chance with each and every pregnancy that they have together that their child will inherit both mutated HSPG2 genes and develop SJS.

Demographics

SJS is a very rare genetic syndrome that affects males and females in many ethnic backgrounds. The exact incidence is unknown. Approximately 100 cases have been reported in scientific publications as of the year 2001. This may not accurately reflect the incidence of SJS, as some persons may not come to medical attention or may be misdiagnosed.

Signs and symptoms

A child born with SJS Type 1A may show no outward signs of the condition at birth. Over the following one to three years, progressive myotonia of the muscles

K E Y T E R M S

Blepharophimosis—A small eye opening without fusion of the upper eyelid with the lower eyelid at the inner and outer corner of the eye.

Consanguineous—Sharing a common bloodline or ancestor.

Contracture—A tightening of muscles that prevents normal movement of the associated limb or other body part.

Myopathy—Any abnormal condition or disease of the muscle.

Myotonia—The inability to normally relax a muscle after contracting or tightening it.

and resulting joint contractures develop. The typical bone problems become obvious and growth in height slows down. These symptoms are evident at birth in children with SJS Type 1B. The following descriptions apply to both SJS Type 1A and Type 1B. However, each person with SJS may be affected to a different degree and their kinds of symptoms may vary.

Head and neck

Myotonia of the muscles in the face causes a tight and fixed facial expression. The eye openings are almost always narrowed and small and the upper and lower eyelids are not joined properly at the corners of the eye (blepharophimosis). The upper eyelid may also appear droopy (ptosis). Nearsightedness (myopia) is present in 50% of patients and occasionally cataracts and lens dislocation may develop in the eye. The mouth is small and lips are puckered due to tight facial muscles. This may lead to speech difficulty. The chin may also be small or set back.

Body

Hernias of the groin and navel areas are often noticed at birth. A hernia is the bulging of a tissue outside of its normal space and a simple operation can usually place it back inside. Pectus carinatum is a common bony deformity of the chest that causes the breast bone to protrude forward. Abnormalities in the growth and development of the bones of the spinal column (vertebrae) lead to scoliosis that usually worsens with age. Development of puberty is most often normal for persons with SJS.

Limbs

Some babies with SJS are born with a dislocation of their hip joint. This is common in infants without SJS as

syndrome Jampel-Schwartz

Schwartz-Jampel syndrome

well. As the muscle disease of SJS progresses, the joints become very stiff. The hips, knees, and elbows in particular have very limited range of motion. These joint contractures worsen until puberty and then tend to stay the same from that point on. Eventually, a wheelchair is needed due to significant limitation of movement. The long bones in the body (i.e.: the thighbone) are bowed and shortened. This can cause a person with SJS to waddle as they walk and to stand in a crouching position. Therefore, an individual with SJS tends to be shorter than 90% of unaffected persons their age. A few have been reported to reach average height. Typically, their arms and legs have an increased amount of body hair as well.

Muscles

The muscles of the body show progressive myotonia, as they remain tight and are unable to relax normally. The muscle bulk may be increased in some areas, such as the thighs, and may waste away in others. As the muscles are unable to function normally, physical activity is restricted and a person may tire very easily.

Central nervous system and behavior

Most individuals with SJS have normal intelligence, although some degree of mental retardation has been reported. Developmental language problems and attention difficulties have also been seen in some cases. Reflexes tend to be slower than normal. A high-pitched voice and drooling may be noticed due to muscle stiffness in the mouth and throat area. This may cause feeding difficulties and choking may be of concern.

Diagnosis

The diagnosis of SJS Type 1A or Type 1B is made mainly by the presence of the symptoms described above. There is no specific biochemical or muscle testing that confirms a suspected diagnosis. Although research studies have identified mutations in the HSPG2 gene in some families, widespread genetic testing is not clinically available as of the year 2001. Such genetic mutations may be unique to each family and therefore may not be found in other persons affected with SJS.

Several different studies may be performed to determine the type and severity of muscle disease when considering a diagnosis of SJS. This may include a muscle biopsy that samples a piece of muscle and examines the appearance of the muscle cells. A muscle biopsy may appear normal or it may show signs of myopathy. A particular chemical, called creatine kinase, can be measured in a person’s blood. Very high levels of creatine kinase usually indicate the presence of muscle disease or wasting. An electromyogram (EMG) is a test that measures

the electrical currents made within an active muscle. The EMG pattern is usually abnormal in persons with SJS. These tests will confirm the presence of muscle disease but there are no specific changes in any of them that are unique to SJS.

The following are some abnormalities of the bones that are frequently noticed on x rays:

•flat and irregularly formed vertebrae

•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:

•Stuve-Wiedemann syndrome (which was previously called SJS Type 2 until it was determined that they were the same condition)

•Freeman-Sheldon syndrome (also known as whistling face syndrome)

•Marden-Walker syndrome

•Kniest dysplasia

•Seckel syndrome

•myotonic dystrophy

•the mucopolysaccharidoses

Treatment and management

There is not a cure for SJS. The treatment involves managing the symptoms of the condition as they develop and supporting the needs of the individual as the disability progresses. Several medical specialists may monitor a person with SJS for particular symptoms or complications. An orthopedic doctor manages the abnormal bone development and may offer surgical options for treatment of hip dislocation, scoliosis, or bone curvature. An ophthalmologist monitors eye problems such as nearsightedness and cataracts, for which glasses and surgery may be available. Cosmetic repair of blepharophimosis by plastic surgery may also be considered.

For those with a mental deficiency, special education programs with options for activities in regular classrooms may offer the best opportunities for learning. Physical therapy may help maintain the greatest possible range of motion of the joints and speech therapy may improve

speech problems due to a small and tight mouth. Physical activities of children are usually limited due to their stiff joints. As the condition progresses, persons with SJS are often wheelchair-bound by their teenage years and occupational therapy may help improve their everyday living skills. Adults who live independently may require some assistance with everyday tasks that their disability prevents them from doing, such as household chores or even bathing.

Prognosis

Individuals with SJS can live well into adulthood despite progressive disability but the average life expectancy is unclear. They are usually wheelchairbound by their teenage or young adult years. Although puberty development may be normal, no reports have been made of an individual with SJS fathering children or carrying a pregnancy.

SJS Type 1B may be fatal in the newborn period due to serious respiratory and feeding problems. As the muscles in the face and neck may be very tight, it can be difficult to place a tube down the throat (intubation) to allow a baby to breathe. Feeding may be a continuous struggle due to problems with or an inability to swallow.

Both types of SJS cause persons to be more prone to develop chest infections and pneumonia. There is also an increased risk for complications from anesthesia, specifically malignant hyperthermia (MH). MH is an abnormal chemical reaction in the body to the use of some anesthesia medications. It causes high fevers, breathing difficulty, rigid muscles and general serious illness. This condition may be life threatening.

Resources

PERIODICALS

Spranger, J., et al. “Spectrum of Schwartz-Jampel Syndrome Includes Micromelic Chondrodysplasia, Kyphomelic Dysplasia, and Burton Disease.” American Journal of Medical Genetics 94 (2000): 287–295.

ORGANIZATIONS

International Center for Skeletal Dysplasia. Saint Joseph’s Hospital, 7620 York Rd., Towson, MD 21204. (410) 3371250.

National Eye Institute. 31 Center Drive, Bldg. 31, Room6A32, MSC 2510, Bethseda, MD 20892-2510. (301) 496-5248. 2020@nei.nih.gov. http://www.nei.nih.gov .

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

.rarediseases.org .

WEBSITES

Genetic Alliance. http://www.geneticalliance.org .

Malignant Hyperthermia Association of the United States.

http://www.mhaus.org .

Muscular Dystrophy Association of the United States.

http://www.mdausa.org .

National Institute of Child Health and Human Development.

http://www.nichd.nih.gov .

Jennifer Elizabeth Neil, MS, CGC

SCIDX see Severe combined immunodeficiency, X-linked

Sclerocornea see Microphthalmia with linear skin defects

I Scleroderma

Definition

Scleroderma is a progressive disease that affects the skin and connective tissue (including cartilage, bone, fat, and the tissue that supports the nerves and blood vessels throughout the body). There are two major forms of the disorder. The type known as localized scleroderma mainly affects the skin. Systemic scleroderma, which is also called systemic sclerosis, affects the smaller blood vessels and internal organs of the body.

Description

Scleroderma is an autoimmune disorder, which means that the body’s immune system turns against itself. In scleroderma, there is an overproduction of abnormal collagen (a type of protein fiber present in connective tissue). This collagen accumulates throughout the body, causing hardening (sclerosis), scarring (fibrosis), and other damage. The damage may affect the appearance of the skin, or it may involve only the internal organs. The symptoms and severity of scleroderma vary from person to person.

Genetic profile

The role of genetics in the transmission in scleroderma is unclear. Some cases clearly run in families, but most occur in people without any family history of the disease.

Demographics

Scleroderma occurs in all races of people all over the world, but it affects about four females for every male. Among children, localized scleroderma is more common,

Scleroderma

Scleroderma

Scleroderma results in thickening and toughening of the skin, which may also become inflamed. (Photo Researchers, Inc.)

and systemic sclerosis is comparatively rare. Most patients with systemic sclerosis are diagnosed between ages 30 and 50. In the United States, about 300,000 people have scleroderma. Young African American women and Native Americans of the Choctaw tribe have especially high rates of the disease.

Signs and symptoms

The cause of scleroderma is still uncertain. Although the accumulation of collagen appears to be a hallmark of the disease, researchers do not know why it occurs. Some theories suggest that damage to blood vessels may cause the tissues of the body to receive an inadequate amount of oxygen—a condition called ischemia. Some researchers believe that the resulting damage causes the immune system to overreact, producing an autoimmune disorder. According to this theory of scleroderma, the immune system gears up to fight an invader, but no invader is actually present. Cells in the immune system, called antibodies, react to the body’s own tissues as if they were foreign. The antibodies turn against the already damaged blood vessels and the vessels’ supporting tissues. These immune cells are designed to deliver potent chemicals in order to kill foreign invaders. Some of these cells dump these chemicals on the body’s own tissues instead, causing inflammation, swelling, damage, and scarring.

Most cases of scleroderma have no recognizable triggering event. Some cases, however, have been traced to exposure to toxic (poisonous) substances. For example, coal miners and gold miners, who are exposed to high levels of silica dust, have above-average rates of scleroderma. Other chemicals associated with the disease include polyvinyl chloride, benzine, toluene, and epoxy resins. In 1981, 20,000 people in Spain were stricken

with a syndrome similar to scleroderma when their cooking oil was accidentally contaminated. Certain medications, especially a drug used in cancer treatment called bleomycin (Blenoxane), may lead to scleroderma. Some claims of a scleroderma-like illness have been made by women with silicone breast implants, but a link has not been proven in numerous studies.

Symptoms of systemic scleroderma

A condition called Raynaud’s phenomenon is the first symptom in about 95% of all patients with systemic scleroderma. In Raynaud’s phenomenon, the blood vessels of the fingers and/or toes (the digits) react to cold in an abnormal way. The vessels clamp down, preventing blood flow to the tip of the digit. Eventually, the flow is cut off to the entire finger or toe. Over time, oxygen deprivation may result in open ulcers on the skin surface. These ulcers can lead to tissue death (gangrene) and loss of the digit. When Raynaud’s phenomenon is the first sign of scleroderma, the next symptoms usually appear within two years.

SKIN AND EXTREMITIES Involvement of the skin leads to swelling underneath the skin of the hands, feet, legs, arms, and face. Swelling is followed by thickening and tightening of the skin, which becomes taut and shiny. Severe tightening may lead to abnormalities. For example, tightening of the skin on the hands may cause the fingers to become permanently curled (flexed). Structures within the skin are damaged (including those producing hair, oil, and sweat), and the skin becomes dry and scaly. Ulcers may form, with the danger of infection. Calcium deposits often appear under the skin.

In systemic scleroderma, the mouth and nose may become smaller as the skin on the face tightens. The small mouth may interfere with eating and dental hygiene. Blood vessels under the skin may become enlarged and show through the skin, appearing as purplish marks or red spots. This chronic dilation of the small blood vessels is called telangiectasis.

Muscle weakness, joint pain and stiffness, and carpal tunnel syndrome are common in scleroderma. Carpal tunnel syndrome involves scarring in the wrist, which puts pressure on the median nerve running through that area. Pressure on the nerve causes numbness, tingling, and weakness in some of the fingers.

DIGESTIVE TRACT The tube leading from the mouth to the stomach (the esophagus) becomes stiff and scarred. Patients may have trouble swallowing food. The acid contents of the stomach may start to flow backward into the esophagus (esophageal reflux), causing a very uncomfortable condition known as heartburn. The esophagus may also become inflamed.