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Tooth and Nail Syndrome

Synonyms of Tooth and Nail Syndrome

  • Dysplasia of Nails With Hypodontia
  • Nail Dysgenesis and Hypodontia

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Tooth and nail syndrome is a rare genetic disorder that belongs to a group of diseases known as ectodermal dysplasia, which group consists of more than 100 separate recognized syndromes. Ectodermal dysplasias typically affect the teeth, nails, hair, and/or skin. Tooth and nail syndrome is characterized by absence (hypodontia) and/or malformation of certain primary (deciduous) and secondary (permanent) teeth occurring in association with improper development (dysplasia) of the nails, particularly the toenails.

In individuals with Tooth and nail syndrome, certain primary teeth and/or several secondary teeth may either be absent or widely spaced and/or conical in shape (coniform). In addition, the nails in young children with the disorder, especially the toenails, may be unusually small and underdeveloped (hypoplastic), with distinctive, abnormal hollowing causing them to appear to be spoon-shaped. Tooth and nail syndrome is inherited as an autosomal dominant genetic trait.

Symptoms

Tooth and nail syndrome, a rare genetic disorder, belongs to a group of diseases known as ectodermal dysplasia (ED). The EDs are rare multisystem disorders that typically affect the teeth, nails, hair, and/or skin. Tooth and Nail syndrome is characterized by absence (hypodontia) and/or malformation of certain primary (deciduous) and secondary (permanent) teeth as well as improper development (dysplasia) of the nails. In some rare cases, affected individuals may also have abnormalities affecting the scalp hair.

In some infants with tooth and nail syndrome, certain primary teeth may be absent or abnormally conical in shape (coniform). In addition, in most children with the disorder, several secondary teeth are also absent and/or malformed. The secondary teeth most often absent include the lower front teeth (mandibular incisors), the teeth next to the incisors in the upper jaw (maxillary canines), and/or the upper and lower molars. The upper portions (crowns) of certain permanant teeth may be cone shaped and, in some cases, the teeth may be widely spaced. Many infants and children with the disorder appear to have a "pouting" or outwardly turned lower lip (everted) due to absence of certain primary and/or secondary teeth.

Individuals with tooth and nail syndrome also have distinctive abnormalities of the toenails and/or fingernails. The nails may be absent at birth and may grow extremely slowly, particularly from infancy to approximately two to three years of age. In addition, when the nails begin to grow, they may be unusually small and underdeveloped (hypoplastic), with distinctive, abnormal hollowing that causes them to appear spoon shaped. In most individuals with tooth and nail syndrome, the toenails are more severely affected than the fingernails. In some cases, the nails may appear normal in older children and adults with the disorder. However, in other cases, the toenails continue to appear abnormally small and/or spoon shaped.

Some individuals with tooth and nail syndrome have scalp hair that is abnormally thin, fine, and brittle.

Causes

Tooth and nail syndrome is inherited as an autosomal dominant genetic trait. The altered gene (mutated) can be tracked to gene map locus 4p16.1. The gene responsible for TNS was identified in 2001 and is termed MSX1. Some mutations appear to encode a protein that is completely nonfunctional. Another nonsense mutation in MSX1 has been associated with oral clefting in addition to tooth agenesis (absence of teeth).

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 4p16.1" refers to band 16.1 on the short arm of chromosome 4. 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.

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.

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 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent 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 percent. The risk is the same for males and females.

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.

Affected Populations

Tooth and nail syndrome affects males and females in equal numbers. Since the disorder was originally described in the medical literature in 1965 (C.J. Witkop), over 30 cases have been reported, with many such cases occurring within several families (kindreds). According to the medical literature, it is estimated that one to two in every 10,000 individuals may be affected by tooth and nail syndrome. Some researchers have reported that the disorder appears to be prevalent among Dutch Mennonites of Canada.

In most cases, tooth and nail syndrome is detected at approximately four or five years of age, when the absence of certain primary (deciduous) teeth and underdevelopment (hypoplasia) of toenails and/or fingernails may be noted.

Related Disorders

Symptoms of the following disorders may be similar to those of tooth and nail syndrome. Comparisons may be useful for a differential diagnosis:

Fried syndrome, an extremely rare genetic disorder, is also a form of ectodermal dysplasia. In infants and children with the disorder, several primary teeth may be absent and/or abnormally small, conical, and peg shaped. According to the medical literature, it is unknown whether the secondary (permanent) teeth are similarly affected. Fried syndrome is also characterized by abnormally thin fingernails; unusually small, thin toenails that may be curved inward (concave); slow growing, fine scalp hair; and/or thin, scanty eyebrows. In addition, affected infants and children may appear to have an outwardly turned lower lip (everted). The symptoms and physical findings associated with Fried syndrome are very similar to those occurring in tooth and nail syndrome. However, in individuals with Fried syndrome, the nails are not as severely affected. Fried syndrome is inherited as an autosomal recessive genetic trait.

Hypohidrotic ectodermal dysplasia (also known as anhidrotic ectodermal dysplasia or Christ-Siemens-Touraine syndrome) is a rare genetic disorder characterized by absence (hypodontia) and/or conical shape of several teeth; absence (aplasia) or underdevelopment (hypoplasia) of the sweat glands; fine, sparse, slow-growing hair and/or premature baldness (alopecia); and/or characteristic facial abnormalities including a prominent forehead, sunken nasal bridge ("saddle" nose), and lips that are turned inside out (everted). Some individuals with the disorder also exhibit short stature, underdevelopment of the glands that secrete tears (lacrimal gland hypoplasia). In most cases, the disorder is inherited as an X-linked genetic trait. In such cases, the disorder is fully expressed in males only, although females who carry a single copy of the disease gene (heterozygotes) may exhibit some mild symptoms associated with the disorder. In other cases, the disorder may be inherited as an autosomal recessive genetic trait. In such cases, males and females are affected in equal numbers. (For more information on this disorder, choose "hypohidrotic ectodermal dysplasia" as your search term in the Rare Disease Database.)

Congenital absence of teeth with taurodontia and sparse hair is an extremely rare genetic disorder characterized by absence of several teeth; distinctive malformations of certain primary and/or secondary molars (taurodontia); unusually sparse, slow-growing hair; and/or other abnormalities. In affected individuals, primary and/or secondary molars may be "prism" shaped. Individuals with the disorder may also have abnormally thin, slow-growing, spoon-shaped fingernails and toenails. According to the medical literature, it is unclear whether this disorder differs from tooth and nail syndrome. However, taurodontia is not usually associated with tooth and nail syndrome. In addition, congenital absence of teeth with taurodontia and sparse hair is inherited as an autosomal recessive genetic trait.

There are additional congenital disorders that may be characterized by abnormalities of the teeth, nails, and/or hair similar to those potentially associated with tooth and nail 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
In some cases, tooth and nail syndrome may be suspected at birth if one or more toenails and/or fingernails are absent. More commonly, the disorder is detected at approximately four or five years of age, when the absence of certain primary (deciduous) teeth and underdevelopment (hypoplasia) of nails may be noted. In some cases, a diagnosis of tooth and nail syndrome may not be confirmed until approximately seven to 15 years of age, when absence and malformation of several secondary (permanent) teeth and nail dysplasia has been verified. A diagnosis of tooth and nail syndrome is confirmed based upon a thorough clinical evaluation and the identification of characteristic physical findings.

Treatment
The treatment of tooth and nail syndrome is directed toward the specific symptoms and findings that are apparent in each individual. Pediatricians; dental surgeons; dental specialists who diagnose and/or correct misalignment (orthodontists); and/or other health care professionals may work together to ensure a comprehensive approach to treatment.

Treatment may primarily consist of dental restoration. Artificial teeth and/or other devices (prosthetics) may be used to replace absent teeth. In addition, braces, dental surgery, and/or other corrective procedures may be undertaken to correct dental abnormalities.

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

Investigational Therapies

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.

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
Email: prpl@cc.nih.gov

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

Tooth and Nail Syndrome Resources

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

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:.

Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison's Principles of Internal Medicine.
16th ed. McGraw-Hill Companies. New York, NY; 2005:.

Gorlin RJ, Cohen MMJr, Hennekam RCM. Eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:.

JOURNAL ARTICLES
Devadas S, Varma B, Mungara J, Joseph T, Saraswathi TR. Witkop tooth and nail syndrome: a case report. Int J Paediatr Dent. 2005;15:364-69.

Mielnik-Blaszczak M, Tomankiewicz M. A rare case of tooth and nail syndrome. Ann Univ Mariae Curie Sklodowska [Med]. 2003;58:306-10.

Wicomb GM, Stephen LX, Beighton P. Dental implications of Tooth-Mail dysplasia (Witkop syndrome): a report of an affected family and an approach to dental management. J Clin Pediatr Dent. 2004;28:107-12.

Jumlongras D, Bei M, Stimson JM, et al. A nonsense mutation in MSX1 causes Witkop syndrome. Am J Hum Genet. 2001;69:67-74.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. witkop Syndrome. Entry Number; 189500: Last Edit Date; 4/19/2004.

Jorgenson RJ. Fried's and Witkop Syndromes (also known as Tooth and nail syndrome). National Foundation for Ectodermal Dysplasia. nd. 2pp.
www.nfed.org/ToothNail.htm.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/05/01 00:00:00 GMT+0

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