Synonyms of Miller Syndrome
- Acrofacial Dysostosis, Postaxial Type
- Acrofacial Dysostosis, Type Genee-Wiedep
- Genee-Wiedemann Syndrome
- Postaxial Acrofacial Dysostosis
Miller Syndrome, also known as postaxial acrofacial dysostosis, is an extremely rare genetic disorder that is apparent at birth (congenital). The disorder is characterized by distinctive craniofacial malformations occurring in association with abnormalities of the outer aspects of the forearms and lower legs (postaxial limb deficiency). Craniofacial malformations may include underdevelopment of the cheekbones (malar hypoplasia); an abnormally small jaw (micrognathia); incomplete closure of the roof of the mouth (cleft palate); small, protruding, "cup-shaped" ears; and/or absence of tissue from (colobomas) and/or drooping of the lower eyelids, exposing the conjunctivae, the thin, delicate mucous membranes that line the eyelids as well as a portion of the eyeballs (ectropion). In infants and children with Miller Syndrome, limb abnormalities may include incomplete development (hypoplasia), webbing (syndactyly), and/or absence of certain fingers and/or toes (e.g., the fifth digits and, in some cases, the fourth and third digits) and/or underdevelopment (hypoplasia) of the bones on the "pinky" side (ulna) and, in some cases, the thumb side of the forearms (radius), causing the forearms to appear unusually short. Additional physical abnormalities may be present in some cases. Miller Syndrome is thought to be inherited as an autosomal recessive genetic trait.
Miller Syndrome is characterized by a lack of development of the lower jaw sometimes with clefting of the soft palate or lip. There is a lack of development of the long bones in the arms and legs causing a shortening of those limbs. The nose may be very broad at the base.
There may be missing, webbed or incompletely formed fingers or toes. Downward slanting of the eyelids and incomplete development (coloboma) of the lower eyelid may result in chronic eye infections. The ears may be cupped forward and be lower on the head than normal. Some deformities may cause breathing and swallowing difficulties in the newborn making insertion of breathing and feeding tubes necessary.
Occasionally, there may be other problems such as heart defects, the backward flow of stomach or kidney contents, extra nipples, problems with joints in the arms, legs and hips, undescended testicles and hearing loss.
Miller Syndrome is thought to be caused by autosomal recessive inheritance. However, the exact mode of transmission is still under investigation. 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 recessive disorders, the condition does not appear unless a person inherits the same defective 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 of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal. The risk is the same for each pregnancy.
Miller Syndrome is a rare disorder that affects males slightly more often than females in the number of cases reported so far.
Symptoms of the following disorders can be similar to those of Miller Syndrome. Comparisons may be useful for a differential diagnosis:
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.)
Nager Acrofacial Dysostosis (Mandibulofacial Dysostosis) is a rare hereditary disorder marked by unusual facial development. Cleft lip and palate, defective development of bones in the jaw and arms, smaller than normal thumbs, hearing loss, and ear deformities are characteristics of this disorder. (For more information on this disorder, choose "Nager" 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
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 then 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 less 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.
Treatment of Miller 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. Tubes may also need to be inserted into the ears. There may be a need for multiple plastic surgeries to correct eye and jaw defects. Physical therapy is necessary for aid in walking and using hands. Surgery and speech therapy is often necessary when cleft palate or lip is present.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
A group at Johns Hopkins Medical School are in the midst of a research project designed to isolate and identify the gene for this disorder. Persons willing to submit blood samples in support of this fundamental goal, may contact:
Ethlyn Wang Jabs, MD
Director, Center for Craniofacial Development and Disorders
Institute of Genetic Medicine
Johns Hopkins University School of Medicine
Other scientists are studying various surgical methods to improve the appearance of patients with craniofacial and other birth defects affecting the head, eyes, and jaw.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Organizations related to Miller Syndrome
Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Co: 1997: 256-57.
Preis S, Raymakers-Buntinx I, Majewski F. Acrofacial dysostosis of an unknown type: nosology of the acrofacial dysostoses. Am J Med Genet. 1995;56:155-60.
Rotten D, Levaillant JM, Martinez H, et al. The fetal mandible; a 2D and 3D sonographic approach to the diagnosis of retrognathia and micrognathia. Ultrasound Obstet Gynecol. 2002;19:122-30.
Howard TD, Guttmacher AE, McKinnon W, et al. Autosomal dominant postaxial polydactyly, nail dystrophy, and dental abnormalities map to the chromosome 4p16, in the region containing the Ellis-van Creveld syndrome locus. Am J Hum Genet. 1997;61:1405-12.
Neumann L, Pelz J. A new observation of two cases of acrofacial dysostosis type Genee-Wiedmann in a family - remarks on the mode of inheritance: report on two sibs. Am J Med Genet. 1996;64:556-62.
Madeira A, Donnai D. Postaxial acrofacial dysostosis syndrome with vertebral segmentation defects. Clin Dysmorphol. 1994;3:171-74.
Chrzanowska K, Fryns JP. Miller postaxial acrofacial dysostosis syndrome. Follow-up data of a family and confirmation of autosomal recessive inheritance. Clin Genet. 1993;43:270.
Chrzanowska K, Fryns JP. Miller postaxial acrofacial dysostosis. The phenotypic changes with age. Genet Couns. 1993;4:131-33.
FROM THE INTERNET
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 263750; Last Update: 3/12/94.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
Copyright ©1992, 1997, 2002
Report last updated: 2008/04/20 00:00:00 GMT+0
NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.