Dentinogenesis imperfecta type III (DGI-III) is one of five distinct, hereditary disorders of dentin development affecting the teeth. Dentin is the hard, bone-like material that makes up most of a tooth and lies under the enamel serving to protect the soft, pulp tissue. These heritable dentin disorders may affect only the teeth or may be associated with the condition known as osteogenesis imperfecta. Whether this association is present is a major criterion in the classification of dentinogenesis imperfecta into three types.
The teeth of people who have inherited one of the DGIs are usually pale-colored and lustrous (opalescent). They are awkwardly formed and situated in the gums; they wear away readily and break easily.
Patients with DGI type I also are affected by osteogenesis imperfecta, and the whites of their eyes (sclera) are blue in color. Patients with DGI type II are NOT affected by osteogenesis imperfecta, but show the other clinical signs. Patients with DGI type III appear to be limited, in large measure, to a population in the region around Brandywine in southern Maryland.
Dentinogenesis imperfecta type III is characterized by rapid erosion of the crowns in baby and permanent teeth. Dental pulp inside several teeth may be exposed. This pulp may be opalescent, smooth, and amber colored. Pulp chambers and root canals may appear very large on X-ray photos of baby teeth. Permanent teeth may have a reduction or even complete loss of the pulp chambers and root canals. Carriers of the gene for this disorder may have teeth that appear normal. However, upon examination their teeth have only an extremely thin ivory layer and an enlarged pulp chamber (shell teeth). Pitting of the tooth enamel may occur in the permanent teeth of patients.
Dentinogenesis imperfecta type III is inherited as an autosomal dominant trait. The abnormal (mutated) gene has been tracked to a site on the long arm of chromosome 4 at band 21.3 (4q21.3). Interestingly, this gene is thought to code for two major dentin proteins — dentin sialoprotein and dentin phosphoprotein. Hence, the gene has been called DSPP for dentin sialophosphoprotein.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. 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.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
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%. The risk is the same for males and females.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
Patients with dentinogenesis imperfecta type III are affected in a ratio of approximately 55 males to 45 females. Symptoms begin as soon as baby teeth erupt. It tends to run in families. The disorder was first found to occur in people who lived in Brandywine, MD, but it can also affect persons of Ashkenazi Jewish heritage.
There do not appear to be reliable numbers for the prevalence or incidence of each of the types of dentinogenesis imperfecta. However as a whole, the disorder affects 1 in 6000 to 8,000 people.
X-rays of the teeth are key to the diagnosis after a thorough family history and clinical examination.
Treatment of children with dentinogenesis imperfecta type III consists of placement of a full set of dental crowns over the teeth. In adults, all teeth may be extracted carefully by elevation and replaced with a full set of dentures. It is recommended that treatment is started early to improve the facial appearance of young patients.
Genetic counseling is recommended for families of children with dentinogenesis imperfecta.
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MacDougall M, Dong J. Dentinogenesis Imperfecta Type III. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:177-78.
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:761.
MacDougall M. Dental structural diseases mapping to human chromosome 4q21. Connect Tissue Res. 2003;44 Suppl 1:285-89.
Dong J, Gu T, Jeffords L, et al. Dentin phosphoprotein compound mutation in dentin sialophosphoprotein causes dentinogenesis imperfecta type III. Am J Med Genet. 2005;132:305-09.
Kim JW, Hu JC, Lee JI, et al. Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II. Hum Genet. 2005;116:186-91.
MacDougall M, Jeffords LG, Gu TT, et al. Genetic linkage of dentinogenesis imperfecta type III locus to chromosome 4q. J Dent Res. 1999;78:1277-82.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Dentinogenesis Imperfecta 1; DGI-I. Entry Number; 125490: Last Edit Date; 2/1/2001.
McKusick VA, ed. Online Mendelian Inheritance in Man(OMIM). The Johns Hopkins University. Dentinogenesis Imperfecta, Shields Type III. Entry Number; 125500: Last Edit Date; 7/14/2005.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Dentin dysplasia, type I. Entry Number; 125400: Last Edit Date;3/18/2004.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Dentin Dysplasia, Type II. Entry Number; 125420: Last Edit Date; 2/3/2004.
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