Witkop?s syndrome

Related Terms

Dysplasia of nails with hypodontia, ectodermal dysplasia, HND, hypodontia-nail dysplasia, MSX1 gene, nail dysgenesis and hypodontia, tooth and nail syndrome, TNS, Witkop syndrome, Witkop tooth and nail syndrome, Witkop's syndrome.

Background

Hypodontia and nail dysgenesis (HND), also known as Witkop tooth and nail syndrome or TNS, is a form of ectodermal dysplasia, which affects the ectoderm, the outer layer of the developing fetus. Because the ectodermal layer develops into many parts of an infant's body, including the nails and teeth, these parts may not develop normally.
HND was first described by a dermatologist named Witkop in 1965 when he observed patients with tooth and nail problems. Patients with HND may also have symptoms that affect the hair. Unlike in many forms of ectodermal dysplasia, however, the sweat glands do not appear to be affected. Symptoms of HND have been found to vary widely among patients.
People with HND may have absent, widely spaced, or cone-shaped teeth with narrow crowns. Fingernails and toenails may be poorly developed, abnormally small, ridged, spoon shaped, brittle, and slow to grow. Rarely, the nails separate from the nail beds and fall off. In people with HND, the toenails are generally more severely affected than the fingernails. Occasionally, sparse scalp hair is observed in HND.
HND is an inherited genetic disorder that is passed down from parents to children. It is caused by a mutation or defect in the MSX1 gene. This gene is known to be involved in tooth development. The disorder follows an autosomal dominant inheritance pattern, meaning only one copy of the defective gene is needed for the disease to appear.
HND is extremely rare with an estimated incidence between one in 1,000 and one in 10,000 people. HND affects males and females in equal numbers. Witkop suggested that the condition was more common among Dutch Mennonites in Canada than other populations.
While there is currently no known cure for HND, treatment focuses on reducing symptoms and managing or preventing complications.

Signs and symptoms

General: As with most forms of ectodermal dysplasia, the teeth, nails, and hair are affected in patients with hypodontia and nail dysgenesis (HND). In addition, symptoms in patients with HND vary widely, from extremely mild to severe. Symptoms of HND may not be apparent until the teeth fail to come in during childhood.
Hair: In some cases, people with HND may have sparse, fine, and brittle hair on the scalp and other parts of the body.
Nails: Fingernails and toenails may be poorly developed, abnormally small, ridged, spoon shaped, brittle, and slow to grow. Rarely, the nails separate from the nail beds and fall off. Generally the toenails are more severely affected than the fingernails in HND. By adulthood, nails may appear normal.
Teeth: People with HND may have absent, widely spaced, or cone-shaped teeth with narrow crowns. The teeth that are most commonly missing in this condition include the incisors and the canines of the upper jaw and the second molars. HND affects both primary (deciduous, or "baby") and secondary (permanent) teeth. While primary teeth are often normal, the condition is often suspected when secondary teeth fail to come in.

Diagnosis

General: Symptoms of hypodontia and nail dysgenesis (HND) range from mild to severe. This variability of symptoms may make diagnosis difficult. HND may be suspected based on the observation of the distinctive qualities of the teeth and nails. In addition, a detailed family history and complete physical exam should be completed.
Genetic testing: If HND is suspected, a genetic test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the MSX1 gene. If it is detected, a positive diagnosis is made.
Prenatal DNA testing: If there is a family history of HND, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose HND. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the MSX1 gene. Miscarriage occurs in about 0.5%-1% of women who undergo this procedure.

Complications

Complications of hypodontia and nail dysgenesis (HND) vary and depend heavily on the severity of the mutation. The most common complications are related to dental problems, especially cavities.

Treatment

There is currently no known cure for hypodontia and nail dysgenesis (HND). Instead, treatment aims to reduce symptoms and prevent complications.
Dental care: People with HND should practice good preventive dental care, including brushing their teeth at least twice a day and flossing once a day, seeing the dentist every 6 months, and avoiding cavity-causing foods and beverages. In addition, crowns or composite fillings may be used on small teeth. Partial or full dentures, implants, or dental surgery may be needed for absent teeth.

Integrative therapies

Currently there is a lack of scientific evidence on the use of integrative therapies for the treatment or prevention of hypodontia and nail dysgenesis (HND). The therapies below have been studied for related conditions such as dental cavities, should be used only under the supervision of a qualified healthcare provider, and should not be used to replace other proven therapies or preventive measures.
Good scientific evidence:
Probiotics: Short-term consumption of probiotic-containing cheese may benefit dental cavities. There is also evidence that the probiotic Lactobacillus rhamnosus GG, when added to milk, may help reduce dental cavities in young children. Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
Unclear or conflicting scientific evidence:
Betel nut: The known toxicities of betel nut use and the availability of other proven products for dental hygiene may cause the risks of betel nut to outweigh the potential benefits. Avoid if allergic to betel nut or other plants of the Palmaceae family. Avoid with asthma and hepatitis B or C. Use cautiously if taking anticholinergic or cholinergic drugs or drugs that may cause extrapyramidal effects (e.g., neuroleptics). Use cautiously with coronary artery disease, high blood pressure, diabetes, extrapyramidal disorders (e.g., Huntington's chorea and Parkinson's disease), urinary incontinence, mental illness, chest pain (angina), blood pressure disorders, irregular heartbeat, heart attack, kidney disease, low calcium levels, cancer, thyroid disease, or vitamin D deficiency. Avoid if pregnant or breastfeeding.
Black tea: There is limited study of black tea as a mouthwash for the prevention of dental cavities. It is not clear whether this therapy has any benefit. Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use with caution in people with diabetes. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked to birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances and insomnia. Infants nursing from mothers consuming more than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism, and irritability. Avoid or use with caution if pregnant or breastfeeding.
Green tea: There is limited study of green tea as a mouthwash for the prevention of dental cavities. It is not clear whether this is a beneficial therapy. Avoid if allergic or hypersensitive to caffeine or tannins. Use cautiously with diabetes or liver disease. Avoid or use with caution if pregnant or breastfeeding.

Prevention

Because hypodontia and nail dysgenesis (HND) is an inherited condition, there is currently no known way to prevent the disease.
Genetic testing and counseling: Individuals who have HND may meet with a genetic counselor to discuss the risks of having children with the disease. Genetic counselors can explain the options and the associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Pre-implantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective MSX1 gene, and only the embryos that are not affected may be implanted and carried to term. Because HND can be detected in an unborn baby, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

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Causes

Genetic mutation: Hypodontia and nail dysgenesis (HND) is caused by a mutation or defect in the MSX1 gene. Although the exact function of this gene is not known, it appears to be expressed in developing nail beds.
Autosomal dominant: HND is inherited, or passed down, in families, as a dominant trait. Individuals receive two copies of most genes, one from the mother and one from the father. For a dominant disorder to appear, only one defective copy of the MSX1 gene is necessary. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
Random occurrence: It is unknown whether HND can occur as the result of a spontaneous genetic mutation with no family history of the disease.

Risk factors

The only known risk factor for hypodontia and nail dysgenesis (HND) is a family history of the disease. HND affects males and females in equal numbers. Witkop suggested the condition was more common among Dutch Mennonites in Canada than other populations.
HND is caused by a mutation or defect in the MSX1 gene. HND is inherited, or passed down, from parents to children as a dominant trait, meaning only one copy of the defective gene is necessary for the disease to appear. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.