$Unique_ID{BRK04036} $Pretitle{} $Title{Nager Syndrome} $Subject{Nager Syndrome Nager Acrofacial Dysostosis Syndrome Acrofacial Dysostosis Nager Type Mandibulofacial Dysostosis AFD Split Hand Deformity-Mandibulofacial Dysostosis Miller Syndrome Treacher Collins Syndrome Goldenhar-Gorlin Syndrome Oral-Digital-Facial Syndrome Juberg-Hayward Syndrome Hemifacial Microsomia } $Volume{} $Log{} Copyright (C) 1992, 1993 National Organization for Rare Disorders, Inc. 892: Nager Syndrome ** IMPORTANT ** It is possible that the main title of the article (Nager Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Nager Acrofacial Dysostosis Syndrome Acrofacial Dysostosis, Nager Type Mandibulofacial Dysostosis AFD Split Hand Deformity-Mandibulofacial Dysostosis Information on the following diseases can be found in the Related Disorders section of this report: Miller Syndrome Treacher Collins Syndrome Goldenhar-Gorlin Syndrome Oral-Digital-Facial Syndrome Juberg-Hayward Syndrome Hemifacial Microsomia General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Nager Syndrome is a rare disorder that may or may not be genetic. Major symptoms may include underdevelopment of the cheek and jaw area of the face. Down-sloping of the opening of the eyes, a smaller than normal jaw, lack or absence of the lower eyelashes, lack of development of the internal and external ear with related hearing problems and cleft palate may also occur. There may be underdevelopment or absence of the thumb, shortened forearms and poor movement in the elbow. Breathing and feeding problems may be present in infants with this syndrome. Symptoms Nager Syndrome is characterized by underdevelopment of the bones of the cheek and jaw area of the face. The eyes may slant downward and there may also be an absence of eyelashes. A smaller than normal jaw, and internal and external ear deformities may also be present. Clefting of the soft and hard palate may occur as well as deformities of the thumbs and arms. Missing, overlapping or webbing of the toes may occur. Clubfeet, hip dislocation and underdeveloped ribs may occasionally be present. Some patients may have heart problems related to the syndrome. There may be hair growing on the sides of the face in an elongated sideburn effect. Feeding, breathing, hearing and speech problems need to be taken care of as soon as possible in order to aid in proper development of the child. This syndrome is very closely related to Miller Syndrome and in some cases has also been misdiagnosed as Treacher Collins Syndrome. Causes The exact cause of Nager Syndrome is not known. However, scientists believe that it may be a genetic disorder inherited either through autosomal recessive or dominant inheritance. 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 fifty percent for each pregnancy regardless of the sex of the resulting child. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from the same trait from each parent. If one 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 of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. Affected Population Nager Syndrome is a very rare disorder that affects males and females in equal numbers. It is apparent at birth and may also be detected prenatally by ultrasound screening. Related Disorders Symptoms of the following disorders can be similar to those of Nager Syndrome. Comparisons may be useful for a differential diagnosis: Miller Syndrome is a very rare genetic disorder. Major symptoms may include shortening of the upper and lower limbs, cupped ears, lower eyelid abnormalities (coloboma) and lack of development of the lower jaw. There is a lack of development of the long bones in the arms and legs causing shortening of those limbs. There is sometimes clefting of the soft palate or lip. (For more information on this disorder, choose "Miller" as your search term in the Rare Disease Database). Treacher Collins Syndrome is characterized by underdevelopment of the cheek (malar), the lower jaw (mandibular) and jaw bones, slanted eyes, notching of lower eyelids, and a receding chin. Underdevelopment of the jaw may cause problems in swallowing or breathing for the newborn. Tubes may have to be inserted to aid the infant in feeding and breathing. The outer upper area of the ear (pinna) may be malformed as well as the external hearing canal (auditory meatus). The eardrum (tympanic membrane) may be replaced with a bony plate. The combination of a longer than normal face with a beaklike nose, receding chin and acute deafness, are characteristic of people with Treacher Collins Syndrome. (For more information on this disorder, choose "Treacher Collins" as your search term in the Rare Disease Database). Goldenhar-Gorlin Syndrome is a rare congenital disorder that involves unusual facial characteristics. The facial structure of people with Goldenhar Syndrome may include partial absence of the upper eyelid or an unusual slant of the eyelid, abnormal shape of the skull (asymmetry), the forehead may be sharply prominent, the nostrils may be absent or closed, the roof of the mouth may be clefted (cleft palate), and there may be abnormal growth of the jaw. Paralysis of the eye muscles may occur. Unusual cysts on the eyeball, cysts in fatty tissue at the edge of the eye and skin growths around the ears (skin tags) may also occur. Malformations of the spinal column including open spine (spina bifida), fusion of the top of the spine to the lower edge of the skull, incomplete development of one side of the spinal column and more than the normal number of vertebrae may also be present. (For more information on this disorder, choose "Goldenhar" as your search term in the Rare Disease Database). Oral-Facial-Digital Syndrome is a rare genetic disorder characterized by episodes of neuromuscular disturbances, split tongue, splits in the jaw, midline cleft lip, overgrowth of the membrane that supports the tongue (frenulum), a broad based nose, vertical folds of skin covering the inner angle where the eyelids meet (epicanthic folds), more than the normal number of fingers and/or toes, and shorter than normal fingers and/or toes. (For more information on this disorder, choose "Oral-Facial-Digital" as your search term in the Rare Disease Database). Juberg-Hayward Syndrome (Orocraniodigital Syndrome) is a rare hereditary disorder characterized by cleft lip and palate, a smaller than normal sized head, deformities of the thumbs and toes, and growth hormone deficiency resulting in short stature. Hemifacial Microsomia (HFM) is a syndrome that affects one in 5,000 births. It can be confused with a Treacher Collins-like Syndrome. However, it is not genetic. Although it can cause abnormalities on both sides of the face, they are always uneven whereas in Treacher Collins Syndrome both sides of the face appear equally affected. The facial nerve is frequently paralyzed in Hemifacial Microsomia. The variety of features of HFM include: underdevelopment of the lower jaw, tilting of the face to one side, ear deformities (microtia), facial nerve weakness in forty percent of patients, cleft-like notching of the affected corner of the mouth (macrostomia), and underdevelopment of the cheek and eye on the affected side of the face. Other common abnormalities include fatty tumors over the eye, abnormalities of the vertebrae and ribs, cleft lip/palate, and heart and kidney abnormalities which are very rare. Therapies: Standard Treatment of Nager Syndrome may consist of surgery to insert breathing and feeding tubes in infants who are unable to breath or eat due to deformities of the palate or jaw. Surgery may be needed on the ears to aid in hearing in those with ear defects. There may be a need for multiple plastic surgeries to correct eye and jaw defects and cleft palate. Physical therapy often is necessary to improve use of hands and feet. Orthopedic surgery may also be necessary to try and correct deformities of the arms, hands, feet or toes. Speech therapy may be needed to aid in hearing and language development. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Scientists are studying various surgical methods to improve the appearance of patients with craniofacial and other birth defects affecting the head, eyes and jaw. 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 birth defects in the future. To participate in this study families with individuals with Miller Syndrome should contact: Eric A. Wulfsberg, M.D. Karen Supovitz, M.S. Division of Human Genetics University of Maryland School of Medicine Baltimore, MD 20201-1703 (410) 328-3815 This disease entry is based upon medical information available through January 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Nager Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The Foundation for Nager & Miller Syndromes 721 South Carlisle St South Bend, IN 46619 (219) 289-5611 NIH/National Institute of Child Health & Human Development (NICHHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 American Cleft Palate Cranial Facial Association 1218 Granview Ave. Pittsburgh, PA 15211 (412) 681-1376 (800) 24CLEFT Forward Face 560 First Ave. New York, NY 10016 (212) 263-5205 (800) 422-FACE FACES National Association for the Craniofacially Handicapped P.O. Box 11082 Chattanooga, TN 37401 (615) 266-1632 Let's Face It Box 711 Concord, MA 01742 (508) 371-3186 National Craniofacial Foundation 3100 Carlisle St., Suite 215 Dallas, TX 75204 (800) 535-3643 American Society for Deaf Children 814 Thayer Ave Silver Spring, MD 20910 (301) 585-5400 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 597. SMITH'S RECOGNIZABLE PATTERNS OF HUMAN MALFORMATION, 4th Ed.: Kenneth L. Jones, M.D., Editor; W.B. Saunders Co., 1988. Pp. 216-217. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 44-45. THE NAGER ACROFACIAL DYSOSTOSIS SYNDROME WITH THE TETRALOGY OF FALLOT, E. Thompson, et al.; J Med Genet, October, 1985, (issue 22 (5)). Pp. 408-410. A SIGNIFICANT FEATURE OF NAGER'S SYNDROME: PALATAL AGENESIS., I.T. Jackson, et al.; Plast Reconstr Surg, August, 1989, (issue 84 (2)). Pp. 219- 226. NAGER ACROFACIAL DYSOSTOSIS: EVIDENCE FOR APPARENT HETEROGENEITY., D.J. Goldstein, et al.; Am J Med Genet, July, 1988, (issue 30 (3)). Pp. 741-746.