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

The intestine becomes sluggish in processing food, causing bloating and pain. Foods are not digested properly, resulting in diarrhea, weight loss, and anemia. Telangiectasis in the stomach or intestine may cause rupture and bleeding.

RESPIRATORY AND CIRCULATORY SYSTEMS The lungs are affected in about 66% of all people with systemic scleroderma. Complications include shortness of breath, coughing, difficulty breathing due to tightening of the tissue around the chest, inflammation of the air sacs in the lungs (alveolitis), increased risk of pneumonia, and an increased risk of cancer. For these reasons, lung disease is the most likely cause of death associated with scleroderma.

The lining around the heart (pericardium) may become inflamed. The heart may have greater difficulty pumping blood effectively (heart failure). Irregular heart rhythms and enlargement of the heart also occur in scleroderma.

Kidney disease is another common complication. Damage to blood vessels in the kidneys often causes a major rise in the person’s blood pressure. The blood pressure may be so high that there is swelling of the brain, causing severe headaches, damage to the retinas of the eyes, seizures, and failure of the heart to pump blood into the body’s circulatory system. The kidneys may also stop filtering blood and go into failure. Treatments for high blood pressure have greatly improved these kidney complications. Before these treatments were available, kidney problems were the most common cause of death for people with scleroderma.

Other problems associated with scleroderma include painful dryness of the eyes and mouth, enlargement and destruction of the liver, and a low-functioning thyroid gland.

Diagnosis

Diagnosis of scleroderma is complicated by the fact that some of its symptoms can accompany other connec- tive-tissue diseases. The most important symptom is thickened or hardened skin on the fingers, hands, forearms, or face. This is found in 98% of people with scleroderma. It can be detected in the course of a physical examination. The person’s medical history may also contain important clues, such as exposure to toxic substances on the job. There are a number of nonspecific laboratory tests on blood samples that may indicate the presence of an inflammatory disorder (but not specifically scleroderma). The antinuclear antibody (ANA) test is positive in more than 95% of people with 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

K E Y T E R M S

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 main supportive protein of cartilage, connective tissue, tendon, skin, and bone.

Connective tissue—A group of tissues responsible for support throughout the body; includes cartilage, bone, fat, tissue underlying skin, and tissues that support organs, blood vessels, and nerves throughout the body.

Fibrosis—The abnormal development of fibrous tissue; scarring.

Limited scleroderma—A subtype of systemic scleroderma with limited skin involvement. It is sometimes called the CREST form of scleroderma, after the initials of its five major symptoms.

Localized scleroderma—Thickening of the skin from overproduction of collagen.

Morphea—The most common form of localized scleroderma.

Raynaud phenomenon/Raynaud disease—A condition in which blood flow to the body’s tissues is reduced by a malfunction of the nerves that regulate the constriction of blood vessels. When attacks of Raynaud’s occur in the absence of other medical conditions, it is called Raynaud disease. When attacks occur as part of a disease (as in scleroderma), it is called Raynaud phenomenon.

Sclerosis—Hardening.

Systemic sclerosis—A rare disorder that causes thickening and scarring of multiple organ systems.

Telangiectasis—Very small arteriovenous malformations, or connections between the arteries and veins. The result is small red spots on the skin known as “spider veins”.

tests, and x ray studies of the gastrointestinal tract. Various blood tests can be given to study kidney function.

Treatment and management

At this time there is no cure for scleroderma. A drug called D-penicillamine has been used to interfere with the abnormal collagen. It is believed to help decrease the degree of skin thickening and tightening, and to slow the

Scleroderma

Scoliosis

progress of the disease in other organs. Taking vitamin D and using ultraviolet light may be helpful in treating localized scleroderma. Corticosteroids have been used to treat joint pain, muscle cramps, and other symptoms of inflammation. Other drugs have been studied that reduce the activity of the immune system (immunosuppressants). Because these medications can have serious side effects, they are used in only the most severe cases of scleroderma.

The various complications of scleroderma are treated individually. Raynaud’s phenomenon requires that people try to keep their hands and feet warm constantly. Nifedipine is a medication that is sometimes given to help control Raynaud’s. Thick ointments and creams are used to treat dry skin. Exercise and massage may help joint involvement; they may also help people retain more movement despite skin tightening. Skin ulcers need prompt attention and may require antibiotics. People with esophageal reflux will be advised to eat small amounts more often, rather than several large meals a day. They should also avoid spicy foods and items containing caffeine. Some patients with esophageal reflux have been successfully treated with surgery. Acid-reduc- ing medications may be given for heartburn. People must be monitored for the development of high blood pressure. If found, they should be promptly treated with appropriate medications, usually ACE inhibitors or other vasodilators. When fluid accumulates due to heart failure, diuretics can be given to get rid of the excess fluid.

Prognosis

The prognosis for people with scleroderma varies. Some have a very limited form of the disease called morphea, which affects only the skin. These individuals have a very good prognosis. Other people have a subtype of systemic scleroderma called limited scleroderma. For them, the prognosis is relatively good. Limited scleroderma is characterized by limited involvement of the patient’s skin and a cluster of five symptoms called the CREST syndrome. CREST stands for:

•C Calcinosis

•R Raynaud’s disease (phenomenon)

•E Esophageal dysmotility (stiffness and malfunctioning of the esophagus)

•S Sclerodactyly (thick, hard, rigid skin over the fingers)

•T Telangiectasis

In general, people with very widespread skin involvement have the worst prognosis. This level of disease is usually accompanied by involvement of other organs and the most severe complications. Although

women are more commonly stricken with scleroderma, men more often die of the disease. The most common causes of death include heart, kidney, and lung diseases. About 65% of all patients survive 10 years or more following a diagnosis of scleroderma.

There are no known ways to prevent scleroderma. People can try to decrease occupational exposure to highrisk substances.

Resources

BOOKS

Aaseng, Nathan. Autoimmune Diseases. New York: F. Watts, 1995.

Gilliland, Bruce C. “Systemic Sclerosis (Scleroderma).” In

Harrison’s Principles of Internal Medicine, ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

“Systemic Sclerosis.” The Merck Manual of Diagnosis and Therapy, ed. Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

PERIODICALS

De Keyser, F., et al. “Occurrence of Scleroderma in Monozygotic Twins.” Journal of Rheumatology 27 (September 2000): 2267-2269.

Englert, H., et al. “Familial Risk Estimation in Systemic Sclerosis.” Australia and New Zealand Journal of

Medicine 29 (February 1999): 36-41.

Legerton, C. W. III, et al. “Systemic Sclerosis: Clinical Management of Its Major Complications.” Rheumatic Disease Clinics of North America, 17 no. 221 (1998).

Saito, S., et al. “Genetic and Immunologic Features Associated with Scleroderma-like Syndrome of TSK Mice. Current Rheumatology Reports 1 (October 1999): 34-37.

ORGANIZATIONS

American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404) 633-3777. http:// www.rheumatology.org .

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

.rarediseases.org .

Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (978) 463-5843 or (800) 722-HOPE. Fax: (978) 463-5809. http://www.scleroderma.org. .

Rebecca J. Frey, PhD

I Scoliosis

Definition

Scoliosis is a side-to-side curvature of the spine of 10 degrees or greater.

Description

When viewed from the rear, the spine usually appears to form a straight vertical line. Scoliosis is a lateral (side-to-side) curve in the spine, usually combined with a rotation of the vertebrae. (The lateral curvature of scoliosis should not be confused with the normal set of front-to-back spinal curves visible from the side.) While a small degree of lateral curvature does not cause any medical problems, larger curves can cause postural imbalance and lead to muscle fatigue and pain. More severe scoliosis can interfere with breathing and lead to arthritis of the spine (spondylosis).

Four out of five cases of scoliosis are idiopathic, meaning the cause is unknown. Children with idiopathic scoliosis appear to be otherwise entirely healthy, and have not had any bone or joint disease early in life. Scoliosis is not caused by poor posture, diet, or carrying a heavy bookbag exclusively on one shoulder.

Idiopathic scoliosis is further classified according to age of onset:

•Infantile. Curvature appears before age three. This type is quite rare in the United States, but is more common in Europe.

•Juvenile. Curvature appears between ages three and 10. This type may be equivalent to the adolescent type, except for the age of onset.

•Adolescent. Curvature appears between ages of 10 and 13, near the beginning of puberty. This is the most common type of idiopathic scoliosis.

•Adult. Curvature begins after physical maturation is completed.

Causes are known for three other types of scoliosis:

•Congenital scoliosis is due to congenital birth defects in the spine, often associated with other structural abnormalities.

•Neuromuscular scoliosis is due to loss of control of the nerves or muscles that support the spine. The most common causes of this type of scoliosis are cerebral palsy and muscular dystrophy.

•Degenerative scoliosis may be caused by degeneration of the discs that separate the vertebrae or arthritis in the joints that link them.

Genetic profile

Idiopathic scoliosis has long been observed to run in families. Twin and family studies have consistently indicated a genetic contribution to the condition. However, no consistent pattern of transmission has been observed in familial cases. As of 2000, no genes have been identi-

A woman with idiopathic scoliosis. (Custom Medical Stock Photo, Inc.)

fied which specifically cause or predispose to the idiopathic form of scoliosis.

There are several genetic syndromes that involve a predispostion to scoliosis, and several studies have investigated whether or not the genes causing these syndromes may also be responsible for idiopathic scoliosis. Using this candidate gene approach, the genes responsible for

Marfan syndrome (fibrillin), Stickler syndrome, and some forms of osteogenesis imperfecta (collagen types I and II) have not been shown to correlate with idiopathic scoliosis.

Attempts to map a gene or genes for scoliosis have not shown consistent linkage to a particular chromosome region.

Most researchers have concluded that scoliosis is a complex trait. As such, there are likely to be multiple genetic, environmental, and potentially additional factors that contribute to the etiology of the condition. Complex traits are difficult to study due to the difficulty in identifying and isolating these multiple factors.

Scoliosis

Scoliosis

K E Y T E R M S

Cobb angle—A measure of the curvature of scoliosis, determined by measurements made on x rays.

Scoliometer—A tool for measuring trunk asymmetry; it includes a bubble level and angle measure.

Spondylosis—Arthritis of the spine.

Demographics

The incidence of scoliosis in the general population is 2-3%. Among adolecents, however, 10% have some degree of scoliosis (though fewer than 1% have curves which require treatment).

Scoliosis is found in both boys and girls, but a girl’s spinal curve is much more likely to progress than a boy’s. Girls require scoliosis treatment about five times as often. The reason for these differences is not known, but may relate to increased levels of estrogen and other hormones.

Signs and symptoms

Scoliosis causes a noticeable asymmetry in the torso when viewed from the front or back. The first sign of scoliosis is often seen when a child is wearing a bathing suit or underwear. A child may appear to be standing with one shoulder higher than the other, or to have a tilt in the waistline. One shoulder blade may appear more prominent than the other due to rotation. In girls, one breast may appear higher than the other, or larger if rotation pushes that side forward.

Curve progression is greatest near the adolescent growth spurt. Scoliosis that begins early on is more likely to progress significantly than scoliosis that begins later in puberty.

More than 30 states have screening programs in schools for adolescent scoliosis, usually conducted by trained school nurses or gym teachers.

Diagnosis

Diagnosis for scoliosis is done by an orthopedist. A complete medical history is taken, including questions about family history of scoliosis. The physical examination includes determination of pubertal development in adolescents, a neurological exam (which may reveal a neuromuscular cause), and measurements of trunk asymmetry. Examination of the trunk is done while the patient is standing, bending over, and lying down, and involves

both visual inspection and use of a simple mechanical device called a scoliometer.

If a curve is detected, one or more x rays will usually be taken to define the curve or curves more precisely. An x ray is used to document spinal maturity, any pelvic tilt or hip asymmetry, and the location, extent, and degree of curvature. The curve is defined in terms of where it begins and ends, in which direction it bends, and by an angle measure known as the Cobb angle. The Cobb angle is found by projecting lines parallel to the vertebrae tops at the extremes of the curve; projecting perpendiculars from these lines; and measuring the angle of intersection. To properly track the progress of scoliosis, it is important to project from the same points of the spine each time.

Occasionally, magnetic resonance imaging (MRI) is used, primarily to look more closely at the condition of the spinal cord and nerve roots extending from it if neurological problems are suspected.

Treatment and management

Treatment decisions for scoliosis are based on the degree of curvature, the likelihood of significant progression, and the presence of pain, if any.

Curves less than 20 degrees are not usually treated, except by regular follow-up for children who are still growing. Watchful waiting is usually all that is required in adolescents with curves of 20-25 degrees, or adults with curves up to 40 degrees or slightly more, as long as there is no pain.

For children or adolescents whose curves progress to 25 degrees, and who have a year or more of growth left, bracing may be required. Bracing cannot correct curvature, but may be effective in halting or slowing progression. Bracing is rarely used in adults, except where pain is significant and surgery is not an option, as in some elderly patients.

There are two different categories of braces, those designed for nearly 24 hour per day use and those designed for night use. The full-time brace styles are designed to hold the spine in a vertical position, while the night use braces are designed to bend the spine in the direction opposite the curve.

The Milwaukee brace is a full-time brace which consists of metal uprights attached to pads at the hips, rib cage, and neck. Other types of full-time braces, such as the Boston brace, involve underarm rigid plastic molding to encircle the lower rib cage, abdomen, and hips. Because they can be worn out of sight beneath clothing, the underarm braces are better tolerated and often leads to better compliance. The Boston brace is currently the

most commonly used. Full-time braces are often prescribed to be worn for 22-23 hours per day, though some clinicians believe that recommending brace use of 16 hours leads to better compliance and results.

Night use braces bend the patient’s scoliosis into a correct angle, and are prescribed for 8 hours of use during sleep. Some investigators have found that night use braces are not as effective as the day use types.

Bracing may be appropriate for scoliosis due to some types of neuromuscular disease, including spinal muscular atrophy, before growth is finished.

Duchenne muscular dystrophy is not treated by bracing, since surgery is likely to be required, and since later surgery is complicated by loss of respiratory capacity.

Surgery for idiopathic scoliosis is usually recommended if:

•the curve has progressed despite bracing

•the curve is greater than 40-50 degrees before growth has stopped in an adolescent

•the curve is greater than 50 degrees and continues to increase in an adult

•there is significant pain

Orthopedic surgery for neuromuscular scoliosis is often done earlier. The goals of surgery are to correct the deformity as much as possible, to prevent further deformity, and to eliminate pain as much as possible. Surgery can usually correct 40-50% of the curve, and sometimes as much as 80%. Surgery cannot always completely remove pain.

The surgical procedure for scoliosis is called spinal fusion, because the goal is to straighten the spine as much as possible, and then to fuse the vertebrae together to prevent further curvature. To achieve fusion, the involved vertebra are first exposed, and then scraped to promote regrowth. Bone chips are usually used to splint together the vertebrae to increase the likelihood of fusion. To maintain the proper spinal posture before fusion occurs, metal rods are inserted alongside the spine, and are attached to the vertebrae by hooks, screws, or wires. Fusion of the spine makes it rigid and resistant to further curvature. The metal rods are no longer needed once fusion is complete, but are rarely removed unless their presence leads to complications.

Spinal fusion leaves the involved portion of the spine permanently stiff and inflexible. While this leads to some loss of normal motion, most functional activities are not strongly affected, unless the very lowest portion of the spine (the lumbar region) is fused. Normal mobility, exercise, and even contact sports are usually all possible after spinal fusion. Full recovery takes approximately six months.

Prognosis

The prognosis for a person with scoliosis depends on many factors, including the age at which scoliosis begins and the treatment received. Most cases of mild adolescent idiopathic scoliosis need no treatment, do not progress, and do not cause pain or functional limitations. Untreated severe scoliosis often leads to spondylosis, and may impair breathing.

Resources

BOOKS

Lonstein, John, et al.,eds. Moe’s Textbook of Scoliosis and Other Spinal Deformities. 3rd ed. Philadelphia: W.B. Saunders, 1995.

Neuwirth, Michael, and Kevin Osborn. The Scoliosis Handbook. New York: Henry Holt & Co., 1996.

ORGANIZATION

National Scoliosis Foundation. 5 Cabot Place, Stoughton, MA 02072 (781)-341-6333.

Jennifer Roggenbuck, MS,CGC

Sebastian platelet syndrome see Sebastian syndrome

I Sebastian syndrome

Definition

Sebastian syndrome is an extremely rare genetic disease that results in impaired blood clotting function and abnormal platelet formation. Another name for Sebastian syndrome is autosomal dominant macrothrombocytopenia with leukocyte inclusions.

Description

Sebastian syndrome is classified as one of the inherited giant platelet disorders (IGPDs). Platelet cells are components of the blood that play a key role in blood clotting. All IGPDs are associated with bleeding disorders due to improper platelet function and increased platelet cell size. Other IGPDs include May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Bernard-Soulier syndrome. Sebastian syndrome is distinguished from these other IGPDs by subtle differences in the platelet and white blood cell structure and by the lack of symptoms other than bleeding abnormalities.

People affected by Sebastian syndrome have mild, non-life-threatening dysfunction of the blood related to

syndrome Sebastian

Sebastian syndrome

K E Y T E R M S

Inherited giant platelet disorder (IGPD)—A group of hereditary conditions that cause abnormal blood clotting and other conditions.

Platelets—Small disc-shaped structures that circulate in the blood stream and participate in blood clotting.

decreased blood clotting function. They may bruise easily or be prone to nosebleeds.

Genetic profile

Sebastian syndrome is inherited as an autosomal dominant trait. Autosomal means that the syndrome is not carried on a sex chromosome, while dominant means that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome.

Genetic studies in the year 2000 proved that Sebastian syndrome is due to a mutation in the gene that encodes a specific enzyme known as nonmuscle myosin heavy chain 9 (the MYH9 gene). The gene locus is 22q11.2, or, the eleventh band of the q arm of chromosome 22. Research has also shown that mutations in the same gene are responsible for May-Hegglin anomaly and Fechtner syndrome, two other inherited giant platelet disorders.

Demographics

Sebastian syndrome is extremely rare and less than 10 affected families have been reported in the medical literature. Due to the very small number of cases, demographic trends for the disease have not been established. Affected individuals have been identified in Caucasian, Japanese, African-American, Spanish, and Saudi Arabian families, so there does not seem to be any clear ethnic pattern to the disease. Both males and females appear to be affected with the same probability.

Signs and symptoms

The symptoms of Sebastian syndrome include a propensity for nosebleeds, bleeding from the gums, mildly increased bleeding time after being cut, and a tendency to bruise easily. Women may experience heavier than normal menstrual bleeding. People with Sebastian syndrome may experience severe hemorrhage after undergoing surgery for any reason. Some individuals with Sebastian syndrome may not have any observable physical signs of the disorder at all.

Diagnosis

Diagnostic blood tests to confirm the decreased blood clotting function seen in Sebastian syndrome may include a complete blood count (CBC) to determine the number of platelets in a blood sample; blood coagulation studies; or platelet aggregation tests.

There are several other disorders, including nongenetic diseases, that can cause symptoms similar to those seen in Sebastian syndrome. A family history of easy bleeding or bruising is an important clue in diagnosing Sebastian syndrome. Once the hereditary nature of the disease is confirmed, establishing a dominant inheritance pattern can separate Sebastian syndrome from other inherited giant platelet disorders.

Microscopic studies of the blood can reveal the enlarged platelets and the specific shape and structure characteristics associated with Sebastian syndrome. These characteristics include a shape that is less disc-like than normal platelets. There are also bluish inclusions, or small foreign bodies, observed in the white blood cells.

Genetic sequencing to confirm the presence of a mutation on the MYH9 gene is another method to positively diagnose Sebastian syndrome, although this would rarely be performed in lieu of other methods.

Treatment and management

No treatment is required for the majority of people affected with Sebastian syndrome. After surgery, platelet transfusion may be required in order to avoid the possibility of hemorrhage. People diagnosed with Sebastian syndrome should be made aware of the risks associated with excessive bleeding.

Prognosis

People with Sebastian syndrome can be expected to have a normal lifespan. The main risk for some patients is the chance of severe bleeding after surgery or injury.

Resources

PERIODICALS

Kunishima, Shinji, et al. “Mutations in the NMMHC-A Gene Cause Autosomal Dominant Macrothrombocytopenia with Leukocyte Inclusions (May-Hegglin Anomaly/Sebastian Syndrome).” Blood (February 15, 2001): 1147-9.

Mhawech, Paulette, and Abdus Saleem. “Inherited Giant Platelet Disorders: Classification and Literature Review.”

American Journal of Clinical Pathology (February 2000): 176-90.

Young, Guy, Naomi Luban, and James White. “Sebastian Syndrome: Case Report and Review of the Literature.”

American Journal of Hematology (April 1999): 62-65.

ORGANIZATIONS

National Heart, Lung, and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. (301) 592-8573. nhlbiinfo @rover.nhlbi.nih.gov. http://www.nhlbi.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

“Sebastian Syndrome.” Online Mendelian Inheritance in Man.

http://www. ncbi . nlm . nih . gov/entrez/dispomim

.cgi?id=605249 (20 April 2001).

Paul A. Johnson

I Seckel syndrome

Definition

Seckel syndrome is an extremely rare inherited disorder characterized by low birth weight, dwarfism, a very small head, mental retardation, and unusual characteristic facial features, including a “beak-like” protrusion of the nose, large eyes, a narrow face, low ears, and an unusually small jaw. Common signs also include abnormalities of bones in the arms and legs.

Description

Seckel syndrome is one of the microcephalic primordial dwarfism syndromes—a category of disorders characterized by profound growth delay. It is marked by dwarfism, a small head, developmental delay, and mental retardation. Abnormalities may also be found in the cardiovascular, hematopoietic, endocrine, and central nervous systems. Children with the disorder are often hyperactive and easily distracted; about half have IQs below 50. Individuals with Seckel syndrome are able to live for an extended period of time.

Seckel syndrome is also known as “bird-headed dwarfism,” Seckel type dwarfism, and nanocephalic dwarfism. The disorder was named after Helmut G.P. Seckel, a German pediatrician who came to the United States in 1936. Dr. Seckel did not discover the syndrome but he authored a publication describing the disorder’s symptoms based on two of his patients.

Genetic profile

Seckel syndrome displays an autosomal-recessive pattern of inheritance. This means that both parents of a

K E Y T E R M S

Microcephalic primordial dwarfism syndromes—

A group of disorders characterized by profound growth delay and small head size.

child with the disorder carry a copy of the Seckel gene— but the parents appear entirely normal. When both parents carry a copy of the Seckel gene, their children face a one in four chance of developing the disorder.

Demographics

Seckel syndrome is extremely rare. Between 1960— the year that Dr. Seckel defined the disorder—and 1999, fewer than 60 cases were reported.

Signs and symptoms

Prenatal signs of Seckel syndrome include cranial abnormalities and growth delays (intrauterine growth retardation) resulting in low birth weight. Postnatal growth delays result in dwarfism. Other physical features associated with the disorder include a very small head (often more severely affected than even the height), abnormalities of bones in the arms and legs, malformation of the hips, a permanently bent fifth finger, failure of the testes to descend into the scrotum (for males) and unusual characteristic facial features, including a “beaklike” protrusion of the nose, large eyes, a narrow face, low ears, and an unusually small jaw. Children with the disorder not only have a small head but also a smaller brain, which leads to developmental delay and mental retardation. Seizures have also been reported.

Diagnosis

Several forms of primordial dwarfism exhibit characteristics similar to those of Seckel syndrome, and it can be challenging for physicians to differentiate true Seckel syndrome from other similar dwarfisms. Physicians do have a set of primary diagnostic criteria to follow—the criteria were first defined by Dr. Seckel in 1960 and later revised (1982) to prevent over-diagnosis of cases.

Most of the primary diagnostic features of Seckel syndrome, which include severe intrauterine growth restriction, a small head, characteristic “bird-like” facies, and mental retardation, are well suited for prenatal sonographic diagnosis. The use of ultrasound examinations to evaluate fetal growth and the careful evaluation of the fetal face and cranial anatomy have proven effective at detecting Seckel syndrome.

syndrome Seckel

Severe combined immunodeficiency

Treatment and management

There is no cure for Seckel syndrome. Certain medications may be prescribed to address other symptoms associated with the disorder.

Prognosis

Children affected with Seckel syndrome can live for an 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) 451-6434. Fax: (516) 671-4055.http://www.hgf1@hgfound.org .

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

.rarediseases.org .

WEBSITES

Alderman, Victoria. “Seckel Syndrome: A Case Study of Prenatal Sonographic Diagnosis.” OBGYN.net Ultrasound (electronic journal) May 1998. http://www.obgyn.net/ us/cotm/9805/cotm9805.htm .

MacDonald, M.R., et al. “Microcephalic Primordial Proportionate Dwarfism, Seckel Syndrome, in a Patient with Deletion of 1q 22-1q 24.3.” http://www.faseb.org/ashg97/f6229

.html .

“Seckel Syndrome.” Online Mendelian Inheritance in Man.

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id= 210600 .

Michelle Lee Brandt

Seckel type dwarfism see Seckel syndrome

Seemanova syndrome see Nijmegen breakage syndrome

Seronegative spondyloarthropathies see

Ankylosing spondylitis

Severe atypical spherocytosis due to ankyrine defect see Spherocytosis, hereditary

I Severe combined immunodeficiency

Definition

SCID, or severe combined immunodeficiency, is a group of rare, life-threatening diseases present at birth

that impair the immune system. Without a healthy immune system the body cannot fight infections and individuals can easily become seriously ill from common infections.

Description

SCID is one type of Primary Immunodeficiency Diseases (PID) and is considered the most severe. There are approximately 70 forms of PID. Primary immunodeficiency diseases are where a person is missing a component of the immune system—either an organ or cells of the immune sytem. Some deficiencies are deadly, while others are mild.

SCID is also known as the “boy in the bubble” syndrome, because living in a normal enviroment can be fatal. SCID initially was called Swiss agammaglobulinemia because it was first described in Switzerland in 1961. Any exposure to germs can pose a risk for infection, including bacterial, viral, and fungal. In the first few months of life, children with SCID become very ill with infections such as pneumonia (infection of the lungs which prevents oxygen from reaching the blood, making breathing difficult), meningitis (infection of the covering of the brain and spinal cord), sepsis (infection in the bloodstream) and chickenpox, and can die within the first year of life, since their immune system is unable to fight off these infections.

Children with SCID do not respond to medications like other children because their immune system does not function properly. They may also not have a developed thymus gland. Medication usually stimulates a person’s immune system to fight infection, but in the case of SCID, the immune system is unable to respond. The immune system is a complex network of cells and organs that protect the body from infection. The thymus and lymphatic system (lymph nodes and lymphatic vessels) house and tranport two very important cells that fight infection: the B and T cells. The bone marrow (center of bones) produces cells that become blood cells as well as cells for the immune system. One type of cell, called lymphocytes or white blood cells, mature in the bone marrow to form “B” cells, while others mature in the thymus to become “T” cells. B and T cells are the two major groups of lymphocytes that recognize and attack infections. Children with SCID have either abnormal or absent B and T cells.

Other infections can be seen in children with SCID including skin infections, yeast infections in the mouth and diaper area, diarrhea, and infection of the liver. Children with SCID fail to gain weight and grow normally. Treatment for SCID is available, however, many children with SCID are not diagnosed in time and die before their first birthday.

immunodeficiency combined Severe

Severe combined immunodeficiency

X-Linked Severe Combined Immunodeficiency

Meningitis

Frequent infections

Sinusitis

Hearing loss

(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, which are also called autosomes. Males and females are equally likely to have an autosomal recessive disease or trait. Recessive means that two copies of the gene are necessary to express the condition. Therefore, a child inherits one copy of the gene from each parent, who are called carriers (because they have only one copy of the gene). Since carriers do not express the gene, parents usually do not know they carry the SCID gene until they have an affected child. Carrier parents have a 1-in-4 chance (or 25%) with each pregnancy, to have a child with SCID.

Severe Combined Immunodeficiency

Recurrent infections

Very small thymus

Problems making antibodies

Needed a bone marrow transplant

(Gale Group)

The last pair of human chromosomes, either two X’s (female) or one X and one Y (male)—determines gender. X-linked means the gene causing the disease or trait is located on the X chromosome. The term “recessive” usually infers that two copies of a gene—one on each of the chromosome pair—are necessary to cause a disease or express a particular trait. X-linked recessive diseases are most often seen in males, however, because they only have one copy of the X chromosome. Therefore, if a male inherits a particular gene on the X chromosome, he expresses the gene, even though he only has a single copy. Females, on the other hand, have two X chromosomes, and therefore can carry a gene on one of their X chromosomes yet not express any symptoms. (Their second X chromosome copy works normally). A mother usually carries the gene for SCID unknowingly, and has a 50/50 chance with each pregnancy to transmit the gene. If the child is a male, he will have SCID; if the child is female, she will be a carrier for SCID like the mother.

New mutations—alterations in the DNA of the gene—can cause disease. In these cases, neither parent has the disease-causing mutation. This may occur because the mutation in the gene happened for the first time only in the egg or sperm for that particular pregnancy. New mutations are thought to happen by chance and are therefore referred to as “sporadic”, meaning, by chance.

Demographics

It is estimated that about 400 children a year are born with some type of primary immunodeficiency disease. Approximately one in 100,000 children are born with SCID each year, regardless of the part of the world the child is from, or the ethnic background of the parents. This disease can affect both males and females depending on its mode of inheritance.

Signs and symptoms

Babies with SCID fail to thrive, are frail, and do not grow well. They have numerous, serious, life-threatening infections that usually begin in the first few months of life. Because they do not respond to medications like other children, they may be on antibiotics for 1-2 months with no improvement before a physician considers a diagnosis of SCID. The types of infections typically include chronic (developing slowly and persisting for a long period of time) skin infections, yeast infections in the mouth and diaper area, diarrhea, infection of the liver, pneumonia, meningitis, and sepsis. They can also have serious sinus and ear infections, as well as a swollen abdomen. Sometimes deep abscesses occur, which are