Information on the following diseases can be found in the Related Disorders section of this report:

• Hallerman-Streiff Syndrome
• De Barsy Syndrome
• Hutchinson-Gilford Progeria Syndrome
• Cockayne Syndrome
• Associated Congenital Disorders (General)

Wiedemann-Rautenstrauch syndrome is characterized by an aged appearance at birth (neonatal progeroid appearance); growth delays; deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy); progressive neurological deterioration; and/or additional abnormalities. The specific symptoms may vary from case to case. Affected individuals will not have all of the symptoms listed below.

In individuals with Wiedemann-Rautenstrauch syndrome, abnormal growth delays may occur before birth (intrauterine growth retardation), particularly during the last three months (third trimester) of fetal development. Affected newborns may be abnormally small and growth delays may continue after birth (postnatally). In addition, in some cases, affected infants may experience swallowing (dysphagia) and feeding difficulties that may contribute to growth delays and failure to thrive.

Infants with Wiedemann-Rautenstrauch syndrome have an aged (progeroid) appearance at birth due to a deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). As a result, the skin may appear unusually thin, fragile, wrinkled, and aged. Certain veins and muscles may be abnormally prominent, particularly those of the forehead. For unknown reasons, as affected infants age, abnormal deposits of fat may accumulate under the skin (subcutaneous) in lower (caudal) areas of the body, particularly around the buttocks, the areas around the genitals and the anus (anogenital area), and the area between the ribs and the hips (flanks). In addition, in infants and children with the disorder, the abdomen may appear unusually large and prominent.

Infants and children with Wiedemann-Rautenstrauch syndrome also have distinctive abnormalities of the head and facial (craniofacial) area. In many cases, the soft spot in the front of the skull (anterior fontanelle) may be abnormally large and wide, and its closure may be unusually delayed. The fibrous joints between certain bones in the skull (cranial sutures) may also be abnormally wide. In addition, in infants with the disorder, bones of the forehead (frontal bones) and the sides of the skull (parietal bones) are abnormally prominent (frontal and biparietal bossing), while the facial bones are unusually small and underdeveloped (hypoplastic).

Such abnormalities may cause the head to appear unusually large (pseudohydrocephalus). In affected infants and children, distinctive facial abnormalities may include underdeveloped cheekbones; an unusually small mouth (microstomia); a prominent chin; and low-set ears that are abnormally angled toward the back of the head (posteriorly angulated). Facial features typically appear unusually small when compared with the large forehead and sides of the skull. In addition, affected infants may have an unusually small, distinctively "beak-shaped" nose that becomes more pronounced with advancing age.

In most infants and children with Wiedemann-Rautenstrauch syndrome, additional craniofacial abnormalities are also present. Affected infants may be born with two to four front teeth (neonatal incisors) that fall out during early infancy. Subsequent tooth development (dentition) may be delayed. In addition, in infants and children with the disorder, the lower eyelids may droop or turn outward (ectropion), exposing the thin, delicate mucous membranes that line the eyelids as well as a portion of the eyeballs (conjunctivae). Affected infants and children may also have unusually sparse scalp hair, eyebrows, and eyelashes.

Infants and children with Wiedemann-Rautenstrauch syndrome may also have distinctive abnormalities affecting the hands, feet, arms, and legs (extremities). Affected individuals may have abnormally thin arms and legs; large hands and feet; and long fingers and toes with unusually small, incompletely developed (atrophic) nails.

Most infants and children with the disorder also have varying degrees of mental retardation, which may range from mild to severe. In addition, during infancy, affected individuals may begin to experience progressive neurological and neuromuscular abnormalities. In most cases, there are severe delays in the acquisition of skills requiring the coordination of physical and mental activities (psychomotor retardation). In addition, in many cases, infants and children with the disorder lack head control; exhibit diminished muscle tone (hypotonia); and have an impaired ability to coordinate voluntary movements of the chest and abdominal areas (truncal ataxia). For example, they may have difficulty controlling the range of movements during certain muscular actions and may experience rhythmic, involuntary tremors when performing certain movements (intention tremor). Infants and children with the disorder may also experience rapid, involuntary, horizontal movements of the eyes (horizontal nystagmus) and limited clearness (acuity) of vision.

Children with this disorder may also develop abnormal side-to-side curvature of the spine (scoliosis). In addition, infants and children with Wiedemann-Rautenstrauch syndrome are often prone to recurrent respiratory infections, which may result in life-threatening complications.
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Wiedemann-Rautenstrauch syndrome is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Some individuals with Wiedemann-Rautenstrauch syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

The specific underlying defect responsible for the disorder remains unknown. However, some researchers suggest that disturbances in bone maturation and hormonal and fatty (lipid) metabolism may play some role. Hormones are natural chemical substances secreted into the bloodstream by certain cells or organs (i.e., endocrine glands) to regulate the activities of another organ or tissue. Metabolism refers to all the chemical processes in the body, including the breakdown of complex substances into simpler ones (catabolism), usually with the release of energy, and processes in which complex substances are built up from simpler ones (anabolism), usually resulting in energy consumption.

In addition, investigators have reported that neurological deterioration observed in individuals with Wiedemann-Rautenstrauch syndrome may be associated with loss of the myelin sheath from nerve fibers (demyelination) within the white substance of the brain (e.g., pure sudanophilic leukodystrophy). Myelin is a whitish fatty substance that forms a protective wrapping or "sheath" around certain nerve fibers (axons) and serves as an electrical insulator, enabling the effective transmission of nerve impulses. "White substance" within the brain and spinal cord (central nervous system) primarily consists of bundles of myelinated nerve fibers.
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Wiedemann-Rautenstrauch syndrome is an extremely rare genetic disorder that appears to affect males and females relatively equally. The disorder was initially described as a distinct entity in 1979 (Wiedemann HR) based upon observation of two unrelated individuals as well as previous reports of two affected sisters in 1977 (Rautenstrauch T). More than 20 cases have been reported in the medical literature to date.
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Symptoms of the following disorders may be similar to those of Wiedemann-Rautenstrauch Syndrome. Comparisons may be useful for a differential diagnosis:

Hallerman-Streiff Syndrome, a rare genetic disorder, is characterized by distinctive craniofacial malformations including an abnormally small head (microcephaly) that is unusually wide (brachycephaly) with a prominent forehead (frontal bossing); an underdeveloped lower jaw (hypoplastic mandible); an unusually small mouth (microstomia); and/or a "beak-shaped" nose. The disorder is also characterized by proportionate short stature (dwarfism); abnormalities of the eyes; malformations of the teeth; and/or other abnormalities. Eye (ocular) abnormalities may include unusually small eyes (microphthalmia); clouding of the lenses of the eyes at birth (congenital cataracts); rapid, involuntary eye movements (nystagmus); crossing of the eyes (strabismus); decreased clarity of vision (visual acuity); and/or other ocular abnormalities. Dental defects may include the presence of certain teeth at birth (neonatal teeth); improper development of tooth enamel (enamel dysplasia); and/or absence (hypodontia or partial adontia), malformation, and/or improper alignment of certain teeth. Individuals with Hallerman-Streiff Syndrome typically have normal intelligence. In most cases, the disorder appears to occur randomly for unknown reasons (sporadically). In other cases, Hallermann-Streiff Syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Hallermann Streiff" as your search term in the Rare Disease Database.)

De Barsy Syndrome (also known as Progeroid Syndrome of De Barsy) is an extremely rare genetic disorder that is apparent at birth. The disorder is characterized by abnormal looseness of the skin (cutis laxa); an aged (progeroid) appearance; clouding of the lenses of the eyes (cataracts); continual, involuntary writhing movements, particularly of the arms and legs (athetosis); and/or short stature. Affected infants and children may also have abnormalities of the head and facial area including an unusually small head (microcephaly) with a prominent forehead (frontal bossing); large, misshapen (dysplastic) ears; thin lips; and/or sparse scalp hair. Additional characteristics often associated with the disorder may include diminished muscle tone (hypotonia), psychomotor retardation, and mental retardation. De Barsy Syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "De Barsy" as your search term in the Rare Disease Database.)

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.)

Cockayne Syndrome is a very rare genetic disorder characterized by growth retardation, abnormal sensitivity to sunlight (photosensitivity), a prematurely aged (progeroid) appearance, and/or other abnormalities. In the classical form of Cockayne Syndrome (Type I), the symptoms are progressive and typically become apparent within the first year of life. In Early Onset Cockayne Syndrome (Type II), associated symptoms and physical findings are apparent at birth (congenital). Affected individuals have distinctive craniofacial abnormalities including an unusually small head (microcephaly), loss of fat underneath the skin, sunken eyes, malformed ears, and a thin, beaked nose. Such abnormalities contribute to a prematurely aged appearance. Individuals with the disorder also exhibit short stature; progressive loss of vision due to degeneration of the nerve-rich membrane lining the eyes (retina); extreme sensitivity to sunlight (photosensitivity); and/or neurological degeneration including progressive mental retardation, movement disturbances, deafness, and loss of intellectual abilities (dementia). In some cases, affected individuals may exhibit premature thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. Cockayne Syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Cockayne" as your search term in the Rare Disease Database.)

There are additional congenital disorders that may be characterized by growth delays, progeroid appearance, craniofacial malformations, mental retardation, progressive neurological and neuromuscular symptoms, and/or other abnormalities similar to those occurring in association with Wiedemann-Rautenstrauch Syndrome. Such disorders usually have other symptoms or physical findings that may differentiate them from Wiedemann-Rautenstrauch Syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

Diagnosis
In some cases, growth retardation, macrocephaly, and/or other characteristic findings suggestive of Wiedemann-Rautenstrauch Syndrome may be detected before birth (prenatally) by ultrasound. In fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus.

In most cases, Wiedemann-Rautenstrauch Syndrome is diagnosed shortly after birth, based upon a thorough clinical evaluation and identification of characteristic physical findings (e.g., small stature, characteristic craniofacial and skeletal malformations, absence or deficiency of subcutaneous fat, etc.). In some cases, specialized tests may also be conducted to detect certain abnormalities potentially associated with the disorder. For example, X-ray studies may reveal and/or confirm wide cranial sutures and/or other abnormalities of cranial bones. In addition, it is possible that computer-assisted tomography (CAT), magnetic resonance imaging (MRI), and/or other specialized tests may reveal widespread loss of the fatty coverings (myelin sheath) on nerve fibers (demyelination) within the white matter of the brain (pure sudanophilic leukodystrophy). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the brain.

Treatment
The treatment of Wiedemann-Rautenstrauch Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who assess and treat disorders of the nervous system (neurologists), physical therapists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Specific therapies for Wiedemann-Rautenstrauch Syndrome are symptomatic and supportive. In some cases, if affected infants and children experience swallowing and feeding difficulties and cannot feed appropriately by mouth, a tube may be surgically inserted into the stomach or a portion of the small intestine (tube feeding) to help provide appropriate nourishment. In addition, affected infants and children should be carefully monitored to help guard against respiratory infections. Genetic counseling will be of benefit for affected individuals and their families.

Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.

ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 3/6/00, Entry Number 264090; Last Edit Date 8/10/96, Entry Number 234100. Last Edit Date 4/18/94, Entry Number 219150; Last Edit Date 2/25/95, Entry Number 176670; Last Edit Date 9/24/94, Entry Number 130070; Last Edit Date 10/21/97, Entry Number 216400.

TEXTBOOKS
Pivnick EK. Neonatal Progeroid Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:238-39.

Champion RH, et al., eds. Textbook of Dermatology. 5th ed. Cambridge, MA: Blackwell Scientific Publications, Inc.; 1992:1817.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:488.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:420-22, 476, 1278-79, 1411-14.

JOURNAL ARTICLES
Thorey F, et al. Kyphoscoliosis in Wiedemann-Rautenstrauch syndrome (neonatal progeroid syndrome). Z Orthop Ihre Grenzgeb. 2003;141:341-4.

Korniszewski L, et al., Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts. Am J Med Genet. 2001;103:144-8.

Pivnick EK, et al. Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review. Am J Med Genet. 2000;90:131-40.

Hoppen T, et al. Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome): case report and review of the literature. Klin Padiatr. 2000;212:71-76.

Stoll C, et al. Wiedemann-Rautenstrauch syndrome. A case report and review of the literature. Genet Couns. 1998;9:119-24.

Courtens W, et al. A probable case of Wiedemann-Rautenstrauch syndrome or neonatal progeroid syndrome and review of the literature. Clin Dysmorphol. 1997;6:219-27.

Arboleda H, et al. Wiedemann-Rautenstrauch neonatal progeroid syndrome: report of three new patients. J Med Genet. 1997;34:433-37.

Bitoun P, et al. The Wiedemann-Rautenstrauch neonatal progeroid syndrome: a case report and review of the literature. Clin Dysmorphol. 1995;4:239-45.

Rautenstrauch T, et al. Neonatal progeroid syndrome (Wiedemann-Rautenstrauch). A follow-up study. Klin Padiatr. 1994;206:440-43.

Mazzarello P, et al. Enzymes of DNA metabolism in a patient with the Wiedemann-Rautenstrauch progeroid syndrome. Ann N Y Acad Sci. 1992;663:440-41.

Castineyra G, et al. Two sibs with Wiedemann-Rautenstrauch syndrome: possibilities of prenatal diagnosis by ultrasound. J Med Genet. 1992;29:434-36.

Toriello HV. Wiedemann-Rautenstrauch syndrome. J Med Genet. 1990;27:256-57.

Hagadorn JI, et al. Neonatal progeroid syndrome: more than one disease? Am J Med Genet. 1990;35:91-94.

Rudin C, et al. The neonatal pseudo-hydrocephalic progeroid syndrome (Wiedemann-Rautenstrauch). Report of a new patient and review of the literature. Eur J Pediatr. 1988;147:433-38.

Martin JJ, et al. The Wiedemann-Rautenstrauch or neonatal progeroid syndrome. neuropathological study of a case. Neuropediatrics. 1984;15:43-48.

Devos EA, et al. The Wiedemann-Rautenstrauch or neonatal progeroid syndrome. Report of a patient with consanguineous parents. Eur J Pediatr. 1981;136:245-48.

Wiedemann HR. An unidentified neonatal progeroid syndrome: follow-up report. Eur J Pediatr. 1979;130:65-70.

Rautenstrauch T, et al. Progeria: a cell culture study and clinical report of familial incidence. Eur J Pediatr. 1977;124:101-11.