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.
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:
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McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 263750; Last Update: 3/12/94.