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Last updated:
August 24, 2020
Years published: 1987, 1989, 1990, 1996, 1998, 2006, 2020
NORD gratefully acknowledges Zachary Cheng and Paulina An, NORD editorial interns from the University of Notre Dame, and Timothy Wright, DDS, MS, Bawden Distinguished Professor, Pediatric and Public Health, Adams School of Dentistry, The University of North Carolina, for assistance in the preparation of this report.
Summary
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 may be apparent at birth due to kinky curly hair that is present in all affected newborns with hair. 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), long bones (i.e., bones in the arms and legs), jaw and spine. These skeletal abnormalities can be seen in children as young as three years of age but are more noticeable with increasing age. Some affected children also exhibit abnormally thin, brittle nails. Most affected children have a relatively normal head shape, but some may have some variation in head shape. The treatment of TDO syndrome is directed toward the specific symptoms that are apparent in each individual.
TDO syndrome is characterized by abnormalities of the hair, teeth, bones, and/or nails. In addition, infants and children with TDO syndrome have tight, kinky or curly hair that may also be unusually dry. As affected individuals enter their 20s or 30s, the hair may straighten or become unusually thin. 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 mineral accumulation (hypomineralization). As a result, the tooth enamel may be abnormally thin, soft, and pitted and often discolored (i.e., yellowish-brown). Hypersensitivity of the teeth is commonly reported. 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. Some affected individuals also exhibit widely spaced teeth; decreased tooth width (microdontia); 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.
Some 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.
Other reported abnormalities include impacted teeth and curvature of fingers (clinodactyly).
TDO syndrome is an autosomal dominant genetic disorder caused by a change (mutation) in the DLX3 gene. Several different mutations in the DLX3 gene have been reported. This gene is a member of the distal-less homeobox gene family. The disorder occurs because of a deletion in this gene that leads to a DLX3 protein product that is shorter than normal and does not function normally. Research has shown that the DLX3 gene plays a role in the patterning of the part of the embryo that leads to the formation of skin, teeth and ectoderm, as well as the formation of bones. This explains the presentation of the symptoms associated with TDO syndrome.
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. The risk is the same for male and female children.
TDO 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 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). Genetic testing for mutations in the DLX3 gene can confirm the diagnosis. To date, researchers have identified nine different mutations in the DLX3 gene that cause TDO. 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 focused on the specific symptoms apparent in each individual and requires the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat diseases of the bones (orthopedists), dental specialists and other health care professionals may be required to address the individual’s clinical symptoms.
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. Treatment is based on keeping teeth from wearing rapidly and exposing the pulp which causes abscess formation. Teeth can be treated with bonding and crowns to preserve the dentition. Dental specialists may obtain 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) such as dental implants 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.
Information on current clinical trials is posted on the Internet at https://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
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
(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.].)
JOURNAL ARTICLES
Whitehouse LLE, Smith CEL, Poulter JA, et al. Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho‐dento‐osseous syndrome. Oral Diseases. 2018;25(1):182-191. doi:10.1111/odi.12955
Jain P, Kaul R, Saha S, Sarkar S. Tricho-dento-osseous syndrome and precocious eruption. Journal of Clinical and Experimental Dentistry. 2017:0-0. doi:10.4317/jced.53348
Zhao N, Han D, Liu H, et al. Senescence: novel insight into DLX3 mutations leading to enhanced bone formation in tricho-dento-osseous syndrome. Scientific Reports. 2016;6(1). doi:10.1038/srep38680
Li Y, Han D, Zhang H, et al. Morphological analyses and a novel de novo DLX3 mutation associated with tricho-dento-osseous syndrome in a Chinese family. European Journal of Oral Sciences. 2015;123(4):228-234. doi:10.1111/eos.12197
Nguyen T, Phillips C, Frazier-Bower S, Wright T. Craniofacial variations in the tricho-dento-osseous syndrome. Clin Genet. 2013 Apr;83(4):375-9. doi: 10.1111/j.1399-0004.2012.01907.x
Al-Batayneh OB. Tricho-dento-osseous syndrome: diagnosis and dental management. Int J Dent. 2012;2012:514692. doi:10.1155/2012/514692
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.
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.
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.
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.
Shapiro SD, Quattromani FL, Jorgenson RJ, et al. Tricho-dento-osseous syndrome: heterogeneity or clinical variability. Am J Med Genet 1983;16:225-236.
INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 190320; Last Update: 05/09/2013. https://www.omim.org/entry/190320 Accessed August 6, 2020.
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