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Tricho Dento Osseous Syndrome

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Synonyms of Tricho Dento Osseous Syndrome

Disorder Subdivisions

General Discussion

Tricho-dento-osseous (TDO) syndrome is an autosomal dominant genetic disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. TDO syndrome is characterized by kinky or curly hair; poorly developed tooth enamel; and unusual thickness and/or denseness (sclerosis) of the top portion of the skull (calvaria) and/or the long bones (i.e., bones in the arms and legs). In some cases, affected individuals also exhibit abnormally thin, brittle nails or premature closure (fusion) of the fibrous joints between certain bones in the skull (craniosynostosis), causing the head to appear abnormally long and narrow (dolicocephaly).

There may be three distinct types of TDO syndrome. Some researchers suggest that these variants may be differentiated mainly by whether the calvaria and/or long bones exhibit abnormal hardening (sclerosis), thickening, and/or density. Other symptoms also vary among the three disorder types.

Symptoms

Tricho-dento-osseous syndrome is characterized by abnormalities of the hair, teeth, bones, and/or nails.

Most infants and children with TDO syndrome have tight, kinky or curly hair that may also be unusually dry. As some affected individuals enter their 20s or 30s, the hair may straighten. In addition, in some cases, the hair is also unusually thin and may fall out. Some individuals with the disorder also have unusually long eyelashes and eyebrows.

All individuals with TDO syndrome have dental abnormalities that affect both the primary (deciduous) and secondary (permanent) teeth but the range of severity is extremely variable. The tooth enamel is underdeveloped (enamel hypoplasia), with diminished calcium accumulation (hypocalcification). As a result, the tooth enamel may be abnormally thin, soft, and pitted and is often discolored (i.e., yellowish-brown). Both the primary and secondary molars may be abnormally shaped (i.e., "prism" shaped), and the chambers within the teeth that contain pulp may be abnormally large (taurodontism). In addition, many teeth may also have unusually short, open roots. As a result, the teeth may be highly prone to decay (dental caries) and infection (abscess) that may cause swelling and pain. In some cases, affected individuals also exhibit widely spaced teeth; absence of certain teeth; premature (precocious) or delayed tooth eruption; and secondary teeth that become impacted in the gums. Affected individuals may lose their teeth early, typically in the second or third decade of life.

Most individuals with TDO syndrome also exhibit thickness and/or denseness (sclerosis) of the top portion of the skull (calvaria) and/or the long bones (i.e., bones in the arms and legs). In addition, in some cases, certain fibrous joints (i.e., sagittal sutures) between bones of the skull may close prematurely (craniosynostosis), causing the head to appear abnormally long and narrow (dolichocephaly). Some individuals with the disorder exhibit an abnormally large head (macrocephaly) with an unusually prominent forehead (frontal bossing) and/or an abnormally square jaw. Abnormal denseness of the calvaria and/or long bones may affect the outer (cortical) layers of bone, causing some affected individuals to be prone to fractures in these areas. The skeletal abnormalities can be seen in children as young as three years of age but are more noticeable with increasing age.

In some cases, individuals with TDO syndrome also exhibit abnormalities of the nails. Fingernails and/or toenails may be unusually thin and brittle. In addition, the upper (superficial) layers of the nail may be prone to splitting.

According to the medical literature, there may be three distinct types of TDO syndrome. Some researchers suggest that these variants may be differentiated mainly by whether the calvaria and/or long bones exhibit thickness and/or density (sclerosis). Other symptoms vary among the three disorder types. It is important to note that there is some confusion in the medical literature concerning which specific physical characteristics may be associated with specific TDO variants.

In TDO-I, the long bones (i.e., arm and leg bones) may be abnormally thick and/or dense, but the bones of the skull (calvaria) tend to be of normal density and thickness. TDO-I may be characterized by premature closure of fibrous joints (particularly the sagittal sutures) between certain bones of the skull (craniosynostosis), causing the head to appear abnormally narrow and long (dolichocephaly). Individuals with TDO-I may also tend to exhibit delayed tooth eruption and, in some cases, abnormally thin, brittle nails that tend to split.

In TDO-II, the calvaria may exhibit abnormal thickness and/or density (sclerosis). Affected individuals with TDO-II may experience premature tooth eruption; in addition, the teeth may not exhibit the discoloration that tends to occur in TDO-I. Individuals with TDO-II may have extremely curly hair that also tends to be abnormally thin and fall out easily. In addition, nail abnormalities may be more striking that those associated with TDO-I, with the nails tending to be extremely thin and brittle, with upper layers that may be prone to splitting.

In TDO-III, although the calvaria may tend to be abnormally thick and dense, the long bones do not appear to exhibit such abnormalities. Affected individuals with TDO-III may also exhibit an unusually large head (macrocephaly) and abnormalities of the bony layer of the skull.

Causes

Tricho-dento-osseous syndrome is an autosomal dominant genetic disorder caused by a mutation in the DLX3 gene located on chromosome 17 at 17q21. This gene is a member of the distal-less homeobox gene family. The disorder occurs as a result of a deletion in this gene that leads to a DLX3 protein product that is shorter than normal and does not function normally.

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 percent for each pregnancy regardless of the sex of the resulting child.

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, "chromosome17q21" refers to band 21 on the long arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Affected Populations

Tricho-dento-osseous syndrome is a rare inherited disorder that affects males and females in equal numbers. Approximately 12 affected families (kindreds) have been reported in the medical literature. TDO syndrome is usually apparent between the ages of approximately six months to one year..

Related Disorders

Symptoms of the following disorders can be similar to those of tricho-dento-osseous syndrome. Comparisons may be useful for a differential diagnosis:

Amelogenesis imperfecta is an inherited disorder in which the tooth enamel is absent (enamel agenesis) or improperly formed (enamel hypoplasia). Many different forms of the disorder have been classified, based upon varying types of enamel defects. Affected individuals may tend to exhibit abnormally thin, soft, pitted, and/or discolored tooth enamel; heightened susceptibility to disease of the structures surrounding and supporting the teeth (periodontal disease); increased sensitivity of the teeth to hot and cold temperatures; and/or early tooth loss. According to the medical literature, one form of amelogenesis imperfecta, called "amelogenesis imperfecta, hypomaturation-hypoplasia type, with taurodontism (AI H-H T)," is characterized by dental abnormalities that may appear identical to those associated with TDO syndrome. Researchers suggest that AI H-H T may be differentiated from TDO syndrome by the absence of the characteristic hair, bone, and/or nail changes associated with TDO syndrome. In addition, in TDO syndrome, the first permanent molars of the lower jaw (mandible) are abnormally shaped (i.e., "prism" shaped). (For more information on this disorder, choose "amelogenesis imperfecta" as your search term in the Rare Disease Database.)

There are additional congenital disorders that may be characterized by malformations of the hair, teeth, bones, and/or nails similar to those potentially associated with TDO syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Tricho-dento-osseous syndrome may be suspected shortly after birth based upon a thorough clinical evaluation, characteristic physical findings (e.g., extremely kinky hair, certain craniofacial abnormalities, dysplastic nails), and advanced imaging techniques. The diagnosis is typically confirmed between the ages of six months to one year, when certain dental abnormalities may become apparent.

Various specialized tests may contribute to diagnosis and characterization of certain associated abnormalities. For example, examination of tooth enamel under a microscope that uses an electron beam (electron microscopy) may reveal an abnormally thin enamel layer with scattered, random pits. Specialized X-ray studies may demonstrate abnormal thickening and/or density (sclerosis) of specific bones (calvaria and/or long bones) and/or other skeletal abnormalities (e.g., craniosynostosis, dolichocephaly).

Treatment
The treatment of TDO 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 diagnose and treat diseases of the bones (orthopedists), dental specialists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Specific therapies for the treatment of TDO syndrome are symptomatic and supportive. Dental abnormalities associated with the disorder may be treated with a variety of techniques. Dental specialists may conduct regular X-rays and take other steps to monitor dental development in the case of premature or delayed tooth eruption, to detect impacted secondary teeth, and/or to help prevent, detect, and/or treat other dental abnormalities. A variety of procedures may be used to restore improperly developed teeth to help prevent decay, abscess, and/or early tooth loss. Artificial teeth and/or other devices (prosthetics) may be used to replace lost or absent teeth. In addition, dental surgery and/or other corrective procedures may be undertaken to correct other dental abnormalities.

Early intervention may be important to ensure that children with TDO syndrome reach their potential. Special services that may be beneficial to affected children may include special social support and other medical, social, and/or vocational services.

Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.

Investigational Therapies

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 National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

The National Foundation for Ectodermal Dysplasias (NFED) is involved with programs in dental schools to provide dental implants to individuals affected by ectodermal dysplasia. Such individuals must have ectodermal dysplasia, be missing a majority of teeth in the lower jaw (mandible), and not have any complicating factors. In addition, they must be willing to participate in the related research project, which requires periodic check-ups. For more information, please contact the National Foundation for Ectodermal Dysplasias, which is listed in the Resources section below.

Organizations related to Tricho Dento Osseous Syndrome

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., dental abnormalities, craniofacial malformations, etc.].)

References

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 190320; Last Update: 3/19/04.

JOURNAL ARTICLES
Crawford PJM and Aldred MJ. Amelogenesis imperfecta with taurodontism and the tricho-dento-osseous syndrome:separate conditions or a spectrum of disease. Clin Genet 1990;38:44-50.

Price JA, Bowden DW, Wright JT, et al. Identification of a mutation in the DLX3 associated with tricho-dento-osseous (TDO) syndrome. Hum Molec Genet 1998;7:563-569.

Price JA, Wright JT, Kula K, et al. A common DLX3 gene mutation is responsible for tricho-dento-osseous syndrome in Virginia and North Carolina families. J Med Genet 1998;35:825-828.

Price JA, Wright JT, Walker, et al. Tricho-dento-osseous syndrome and amelogenesis imperfecta with taurodontism are genetically distinct conditions. Clin Genet 1999;56:35-40.

Shapiro SD, Quattromani FL, Jorgenson RJ, et al. Tricho-dento-osseous syndrome:herogeneity or clinical variability. Am J Med Genet 1983;16:225-236.

Wright JT, Kula K, Hall K, et al. Analysis of the tricho-dento-osseous syndrome genotype and phenotype Am J Med Genet 1997;72:197-204.

Report last updated: 2008/04/22 00:00:00 GMT+0