Tricho Dento Osseous Syndrome

Tricho Dento Osseous Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Tricho Dento Osseous Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • TDO Syndrome

Disorder Subdivisions

  • TDO-I
  • TDO-II
  • TDO-III

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..

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.

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.

Resources

National Foundation for Ectodermal Dysplasias

6 Execuitive Drive

Suite 2

Fairview Hiights, IL 62208

Tel: (618)566-2020

Fax: (618)566-4718

Email: info@nfed.org

Internet: http://www.nfed.org



Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240

USA

Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643

Email: contactCCA@ccakids.com

Internet: http://www.ccakids.com



FACES: The National Craniofacial Association

PO Box 11082

Chattanooga, TN 37401

Tel: (423)266-1632

Fax: (423)267-3124

Tel: (800)332-2373

Email: faces@faces-cranio.org

Internet: http://www.faces-cranio.org



AmeriFace

P.O. Box 751112

Limekiln, PA 19535

USA

Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209

Email: info@ameriface.org

Internet: http://www.ameriface.org



NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675

USA

Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/



NIH/National Institute of Dental and Craniofacial Research

Building 31, Room 2C39

31 Center Drive, MSC 2290

Bethesda, MD 20892

USA

Tel: (301)496-4261

Fax: (301)480-4098

Tel: (866)232-4528

Email: nidcrinfo@mail.nih.gov

Internet: http://www.nidcr.nih.gov/



Craniofacial Foundation of America

975 East Third Street

Chattanooga, TN 37403

Tel: (423)778-9176

Fax: (423)778-8172

Tel: (800)418-3223

Email: terry.smyth@erlanger.org

Internet: http://www.craniofacialfoundation.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.