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			Progeria Click here for more information on Progeria. ********* Hutchinson-Gilford Progeria Syndrome Symptoms of the following disorder may be similar to those of Wiedemann-Rautenstrauch Syndrome. Comparisons may be useful for a differential diagnosis: Hutchinson-Gilford Progeria Syndrome is a very rare progressive disorder of childhood characterized by premature aging (progeria), growth delays occurring in the first year of life resulting in short stature and low weight, deterioration of the layer of fat beneath the skin (subcutaneous adipose tissue), and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated nonhealing fractures, a progressive aged appearance of the skin, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. In most cases, affected individuals experience premature, widespread thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. Hutchinson-Gilford Progeria Syndrome is thought to be due to an autosomal dominant genetic change (mutation) that occurs for unknown reasons (sporadic). (For more information on this disorder, choose “Hutchinson-Gilford” as your search term in the Rare Disease Database.) BCHealthGuide http://www.bchealthguide.org ******** Hutchinson-Gilford Disease Also known as: Gilford’s syndrome Hutchinson-Gilford progeria Hutchinson-Gilford syndrome Souques-Charcot syndrome a variant of this syndrome) Synonyms: Premature aging syndrome, premature senility syndrome, progeria, progeria infantum, progeria infantilis, senilism syndrome Associated persons: Jean-Martin Charcot Hastings Gilford Sir Jonathan Hutchinson Alexandre-Achille Souques Description: A very rare disease of premature aging in young children, characterized mainly by a birdlike, “wizened old man” facial appearance, premature bodily aging (progeria) and dwarfism. The children have large skulls, bird-like features, atrophy of muscles and skin, loss of subcutaneous fat, high serum lipid levels and early atherosclerotic changes in the vessels. The child is normal at birth. Intelligence is usually normal. The average age of death is 16 years, but survivors until 26 years have been recorded. Occur in children of both sexes. Death is usually caused by the effects of arteriosclerosis. Etiology and mode of genetic transmission (if any) is unknown. Hutchinson-Gilford progeria was discovered in 1886 by Jonathan Hutchinson. He documented the clinical features of a boy aged 6 years who had congenital absence of the hair and atrophy of the skin. Hastings Gilford followed up this patient and another, and in 1897 recognized it as a clinical entity and introduced the term “progeria” from the Greek work meaning “prematurely old.” In his case report published in 1904 he provided a set of pictures of the disorder from infancy to the age of 17 years, in which the characteristic alopecia, fat loss and premature aging are clearly depicted. A possible earlier report in Phlegontis’s Tralliani de Mirabilibus relates to Craterus, who went from infancy to old age and death, within a life span of seven years. Another classical description appeared in the St. James Gazette concerning Hopkin Hopkins, a well-known exhibitionist: “March 9^th, 1754. Died in Glamorganshire of mere old age and a gradual decay of nature at 17 years and 2 months, Hopkin Hopkins, the little Welshman, lately shown in London. He never weighed more than 17 pounds, but for 3 years past, no more than 12.” E.P. Waldorp and E.B. del Castllo used the conjoined eponym “Hutchinson-Gilford syndrome” in 1928 and in 1972 De Busk reviewed 60 cases under this title. The genetic basis of progeria is uncertain; although a few instances of affected siblings have been reported, the majority of cases have been sporadic. Information from: http://www.whonamedit.com ******** PROGERIA, HUTCHINSON GILFORD Synonyms: - Gilford syndrome - HGPS - Hutchinson-Gilford syndrome - Premature Senility syndrome - Progeria of Childhood - Souques-Charcot syndrome Disorder Subdivisions: None Related Disorders List: - Hallermann-Streiff syndrome - Gottron’s syndrome - Rautenstrauch-Wiedemann syndrome, neonatal - DeBarsy syndrome - Progeroid syndrome with Ehlers-Danlos features - Werner syndrome General Discussion Progeria, or the Hutchinson-Gilford Progeria syndrome, is a rare disease of childhood with striking features resembling premature aging. Children with progeria usually have a normal appearance in early infancy. At approximately six months of age, affected children may begin to experience profound growth delays, resulting in short stature and low weight. They may also develop a distinctive facial appearance characterized by a disproportionately small face in comparison to the head; an underdeveloped jaw (micrognathia); malformation and crowding of the teeth; abnormally prominent eyes; a small, “beak-like” nose; and absent earlobes. In addition, by the second year of life, the scalp hair, eyebrows, and eyelashes are lost (alopecia), and the scalp hair may be replaced by small, downy, white or blond hairs. Additional characteristic features include unusually prominent veins of the scalp, loss of the layer of fat beneath the skin (subcutaneous adipose tissue), defects of the nails, joint stiffness, skeletal defects, and/or other abnormalities. According to reports in the medical literature, individuals with Hutchinson-Gilford Progeria syndrome develop premature, widespread thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications during childhood, adolescence, or early adulthood. In most patients, Hutchinson-Gilford Progeria syndrome is caused by new genetic changes that occur randomly for unknown reasons (sporadic). These mutations are thought to be transmitted as an autosomal dominant trait. Symptoms Newborns with Hutchinson-Gilford Progeria syndrome may have certain suspicious findings may be present at birth, such as unusually taut, shiny, hardened (i.e., “scleroderma-like”) skin over the buttocks, upper legs, and lower abdomen; bluish discoloration of the skin and mucous membranes within the midportion of the face (midfacial cyanosis); and/or a “sculptured” nose. Profound, progressive growth retardation usually becomes evident by approximately six months of age, resulting in short stature and weight that remains extremely low for height. According to reports in the medical literature, affected children who are 10 years of age typically have a height approximately that of an average three-year-old child. By the second year of life, there is also underdevelopment (hypoplasia) of the facial bones and the lower jaw (micrognathia). The face appears disproportionately small in comparison to the head, and bones of the front and the sides of the skull (cranium) are unusually prominent (frontal and parietal bossing). Affected children typically have additional, characteristic facial features, including a small, thin, potentially “beaked” nose; unusually prominent eyes; small ears with absent lobes; and thin lips. Dental abnormalities may also be present, such as delayed eruption of the primary (deciduous) and secondary (permanent) teeth; irregularly formed, small, discolored, and/or absent teeth; and/or an unusually increased incidence of tooth decay (dental caries). In addition, abnormal smallness of the jaw may result in dental crowding. In children with the disorder, the scalp hair becomes sparse and is typically lost (alopecia) by approximately two years of age. Scalp hair may be replaced by fine, downy, white or blond hairs that, in some cases, may persist throughout life. In addition, the eyebrows and eyelashes may also be lost during early childhood. Hutchinson-Gilford Progeria syndrome is also characterized by distinctive skin abnormalities. As discussed above, newborns with the disorder may have “scleroderma-like” skin changes over the buttocks, thighs, and lower abdomen. In addition, beginning to infancy, there is a gradual, almost complete loss of the layer of fat beneath the skin (subcutaneous adipose tissue), and veins in certain areas of the body, particularly over the scalp and thighs, become abnormally prominent. In affected children, the skin acquires an abnormally aged appearance with areas that are unusually thin, dry, and wrinkled and/or unusually shiny and taut. In addition, brownish skin blotches may tend to develop with increasing age over sun-exposed areas of the skin. Affected children also typically have defects of the nails, such as fingernails and toenails that are yellowish, thin, brittle, curved, and/or absent. Children with Hutchinson-Gilford Progeria syndrome also have distinctive skeletal defects. These may include delayed closure of the “soft spot” at the front of the skull (anterior fontanelle), an abnormally thin “dome-like” portion of the skull (calvaria), and/or absence of certain air-filled cavities within the skull that open into the nose (paranasal or frontal sinuses). In many cases, affected children also have short, thin collarbones (clavicles) narrow shoulders; thin ribs; and a narrow or “pear-shaped” chest (pyriform thorax) with a prominent abdomen. In addition, the long bones of the arms and legs may appear unusually thin and fragile and be prone to fractures, particularly the bones of the upper arms (humeri). In many children with Hutchinson-Gilford Progeria syndrome, skeletal abnormalities include degenerative changes (osteolysis) that may affect the collarbones (clavicles); bones of the ends of the fingers (terminal phalanges), causing the fingers to appear unusually short and “tapered”; and/or the hip socket (acetabulum). Degenerative changes of the hip socket may result in a hip deformity in which there is an abnormal increase in the angle of the thigh bone (coxa valga), hip pain, and hip dislocation. In addition, in many affected children, abnormal fibrous tissue progressively forms around certain joints (periarticular fibrosis), such as those of the hands, feet, knees, elbows, and spine, causing unusual prominence, stiffness, and limited movement of affected joints. Due to stiffness of the knees, progressive hip deformity (coxa valga), and other associated musculoskeletal abnormalities, children with the disorder tend to have a characteristic, widely based, “horse-riding stance” and a shuffling manner of walking (gait). The disorder is also associated with generalized loss of bone density (osteoporosis), a condition that may cause or contribute to repeated fractures following minor trauma. Additional symptoms and findings may also be associated with Hutchinson-Gilford Progeria syndrome. These may include a distinctive, high-pitched voice; absence of the breast or nipple; absence of sexual maturation; hearing impairment; and/or other abnormalities. According to reports in the medical literature, affected children as young as five years may develop widespread thickening and loss of elasticity of artery walls (arteriosclerosis). Such changes may be most evident in particular blood vessels, such as the arteries that transport oxygen-rich blood to heart muscle (coronary arteries) and the major artery of the body (aorta). Additional findings may include enlargement of the heart (cardiomegaly) and abnormal heart sounds (i.e., as heard during a physician’s examination with a stethoscope) due to altered blood flow through valves or chambers of the heart (cardiac murmurs). During childhood or adolescence, progressive arteriosclerosis may lead to episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks); obstructed blood flow within blood vessels of the brain (cerebrovascular occlusion); progressive inability of the heart to effectively pump blood to the lungs and the rest of the body (heart failure); and/or localized loss of heart muscle caused by interruption of its blood supply (myocardial infarction or heart attack). In individuals with Hutchinson-Gilford Progeria syndrome, progressive arteriosclerosis and associated cardiovascular abnormalities may result in potentially life-threatening complications during childhood, adolescence, or young adulthood. Causes The exact cause of Hutchinson-Gilford Progeria syndrome is not known. Some researchers suggest that, in most cases, the disorder occurs as the result of new genetic change(s) (mutation[s]) that occur randomly for unknown reasons (sporadic). Such mutations are thought to be transmitted as autosomal dominant traits. According to the medical literature, advanced parental age has been reported in many cases. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The specific underlying cause of the accelerated aging associated with Hutchinson-Gilford Progeria syndrome is not yet known. Many researchers suggest that the normal aging process is due to cumulative cellular damage resulting from ongoing chemical (metabolic) processes within bodily cells. According to this theory, certain compounds called free radicals are produced during chemical reactions in the body. The increasing accumulation of free radicals within bodily tissues is thought to eventually cause damage to and impaired functioning of cells, ultimately resulting in aging. Certain enzymes (known as antioxidant enzymes) are believed to play a role in keeping the aging process “in check” by promoting the elimination of damaging free radicals. Enzymes are proteins produced by cells that accelerate the rate of chemical reactions in the body. Some researchers indicate that reduced activity of certain enzymes may play a role in causing accelerated aging in individuals with Hutchinson-Gilford Progeria syndrome. In one study, skin cells (fibroblasts) obtained from individuals with progeria were compared with skin cells from individuals without the disease. In the fibroblasts of those with progeria, the activity levels of certain primary antioxidant enzymes (e.g., gluthathione peroxidase [GPx]), catalase [CAT]), were significantly lower than the levels present in health fibroblasts. Further research is necessary to determine the implications of such findings. Affected Populations Hutchinson-Gilford Progeria syndrome is a rare disorder that appears to affect males and females equally. Since the disorder was originally described in the medical literature in 1886 (J. Hutchinson) and 1897 (H. Gilford), approximately 100 cases have been reported. Estimates indicate that Hutchinson-Gilford Progeria syndrome affects one infant in approximately eight million births. Two sets of affected identical twins have been reported in the literature. Related Disorders Symptoms of the following disorders can be similar to those of Hutchinson-Gilford Progeria syndrome. Comparisons may be useful for a differential diagnosis: Hallermann-Streiff syndrome is a rare inherited disorder characterized by short stature and characteristic facial features. Newborns with this disorder have a “bird-like” face, a receding jaw, and a narrow beaked nose. Eyebrows and hair on the head may be absent or underdeveloped. The eyeballs and corneas are usually abnormally small. Wrinkled skin may give newborns with Hallermann-Streiff syndrome an appearance that is similar to that of Hutchinson-Gilford Progeria syndrome. (For more information choose Hallermann-Streiff as your search term in the Rare Disease Database). Gottron’s syndrome (acrogeria) is a mild, inherited form of premature aging (progeria) characterized by abnormally small hands and feet with thin and delicate skin. From infancy on, children with this disorder appear older than their actual age. The skin is unusually thin and parchment-like on the hands and feet. The hands and feet remain abnormally small into adulthood. (For more information choose “Gottron” as your search term in the Rare Disease Database). Rautenstrauch-Widemann syndrome is an extremely rare disorder characterized by premature aging. Newborns with this disorder appear similar to newborn children with Hutchinson-Gilford Progeria syndrome. Symptoms may include spare hair, noticeable veins on the head, prominent nose, low-set ears, a receding jaw, and the absence of fat under the skin. Children are short for their age and have some degree of mental retardation. This disorder is inherited as an autosomal recessive genetic trait. DeBarsy syndrome is a rare disorder that is inherited as an autosomal recessive genetic trait. The main characteristics include degeneration of the elastic tissue in the skin (Cutis Laxa), involuntary movements of the arms and legs (athetosis), cloudy corneas of the eyes, large prominent ears, and loss of muscle tone. Other symptoms may include unusual flexibility of the small joints, a forehead that protrudes outward (frontal bossing), and/or short stature. The loss of elasticity of the skin leads to an aged wrinkled appearance. Newborn children with this disorder may look like newborns with Hutchinson-Gilford Progeria syndrome. (For more information choose “DeBarsy as your search term in the Rare Disease Database). Progeroid syndrome with Ehlers-Danlos Features is an extremely rare genetic disorder characterized in newborns by a “progeria-like” (progeroid) appearance. The skin may be wrinkled leading to an aged appearance. Other symptoms include spare eyebrows, scanty eyelashes, multiple birthmarks, and extremely fragile skin which bruises easily. Some children with this disorder may have low-set prominent ears, a receding chin, and/or irregular teeth. Werner syndrome is a form of premature aging (Progeria) which begins during adolescence or early adulthood and results in the appearance of old age by the age of 30 to 40 years. (For more information choose “Werner” as your search term in the Rare Disease Database). Standard Therapies** Diagnosis - Hutchinson-Gilford Progeria syndrome is usually diagnosed during the first or second year of life based upon a thorough clinical evaluation, characteristic physical findings, a careful patient history, and certain specialized tests. More rarely, the disorder may be suspected at birth based upon recognition of certain suspicious findings (e.g. “scleroderma-like” skin over the buttocks, thighs, lower abdomen; midfacial cyanosis; “sculptured” nose). Specialized imaging tests may be conducted to confirm or characterize certain skeletal abnormalities potentially associated with the disorder, such as degenerative changes (osteolysis) of certain bones of the fingers (terminal phalanges) and/or the hip socket (acetabulum). In addition, thorough cardiac evaluations and ongoing monitoring may also be performed (e.g., clinical examinations, X-ray studies, specialized cardiac tests) to assess associated cardiovascular abnormalities and determine appropriate disease management. In some individuals with Hutchinson-Gilford Progeria syndrome, blood tests may reveal elevated levels of certain fatty compounds (e.g., cholesterol, phospholipids). In addition, specialized laboratory tests (assays) performed on cultured skin cells (fibroblasts) may show reduced activity levels of certain primary antioxidant enzymes (e.g., gluthathione peroxidase [GPx], catalase [CAT]) or other abnormalities. Treatment The treatment of Hutchinson-Gilford Progeria syndrome is directed toward the specific symptoms that are apparent in each individual. Disorder management may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected child’s treatment. Such specialists may include pediatricians; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and other related tissues (orthopedists); physicians who diagnose and treat abnormalities of the heart and its major blood vessels; physical therapists; and/or other health care professionals. Specific therapies for individuals with Hutchinson-Gilford Progeria syndrome are symptomatic and supportive. For example, in those with episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks), treatment may include the use of certain medications that may help to minimize or manage such symptoms. Investigational Therapies Since some studies suggest that some symptoms of Hutchinson-Gilford Progeria may be due to the production of a biologically inactive form of growth hormone and treatment of affected children with recombinant human growth hormone (hGH) has been attempted. More study is needed to determine the long-term safety and effectiveness of this drug for the treatment of Hutchinson-Gilford Progeria syndrome. BC Health Guide http://www.bchealthguide.org ********** More about Progeria .... Progeria: A paper by Debra Horng Genetics and Embryology, 6.0 19 March 1999 The Genetics of Progeria Biol. 2402 - Anatomy & Physiology Richland College, Spring 2001 Class Project Web Project Members: Megan Gardner, Lindsey Leger, Stacie Stricklin Therapy for Progeria Biol. 2402 - Anatomy & Physiology Richland College, Spring 2001 Class Project Web Project Members: Amanda Williams, Tia Furcht, Kristin Kosarek Hutchinson-Gilford Syndrome Biol. 2402 - Anatomy & Physiology Richland College, Spring 2001 Class Project Web Project Members: Deanna McCall, Debi Blow, Rosemary Kavishe, Nicole Rainer Causes of Death Biol. 2402 - Anatomy & Physiology Richland College, Spring 2001 Class Project Web Project by: Christann Lall Cellular Mechanisms of Progeria** Biol. 2402 - Anatomy & Physiology Richland College, Spring 2001 Class Project Web Project Members: Ami Stovall, Amanda Dean, Helen Chen
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