Tricho-Dento-Osseous Syndrome (TDO)

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Description

Tricho-Dento-Osseous Syndrome (TDO) is a rare genetic disorder characterized by abnormalities in the development of hair, teeth, and bones. This syndrome is often inherited in an autosomal dominant pattern, meaning a single copy of the altered gene from one parent is sufficient to cause the disorder. The severity of TDO can vary widely among affected individuals, even within the same family. Individuals with TDO may experience a range of symptoms, from mild to severe, depending on the specific gene mutation involved.

Genes Involved

Several genes have been linked to TDO, with different mutations resulting in variations in symptom severity. Some of the main genes involved include:

• DLX3: Mutations in this gene are associated with the most common form of TDO, known as TDO1.
• KRT75: Mutations in this gene are linked to TDO2, characterized by hair and nail abnormalities.
• FAM20C: Mutations in this gene can cause TDO3, characterized by enamel hypoplasia and bone abnormalities.
• RUNX2: Mutations in this gene are associated with TDO4, characterized by bone abnormalities and delayed tooth eruption.

Recognizing the Signs and Symptoms

The hallmark features of TDO involve the following:

• Hair:

  • Brittle, dry, and sparse hair
  • Hair shafts may be abnormally thin or have a twisted appearance
  • Hair loss or alopecia

• Teeth:

  • Enamel hypoplasia (incomplete or thin enamel)
  • Delayed tooth eruption
  • Discolored teeth
  • Small or misshapen teeth
  • Increased risk of dental caries

• Bones:

  • Osteosclerosis (increased bone density)
  • Bone deformities in the skull, jaws, and extremities
  • Joint pain
  • Short stature (in some cases)

Other symptoms that may occur in individuals with TDO include:

• Skin:

  • Dry skin
  • Increased skin pigmentation

• Nails:

  • Brittle nails

• Eyes:

  • Myopia (nearsightedness)
  • Cataracts
  • Glaucoma

Causes

TDO is primarily caused by mutations in genes responsible for regulating the development and function of hair, teeth, and bones. These mutations are often inherited from a parent, following an autosomal dominant inheritance pattern. In some cases, the mutation might be a spontaneous occurrence, meaning it is not inherited.

Inheritance/recurrence risk

TDO is usually inherited in an autosomal dominant pattern. This means that if one parent has the gene mutation, there is a 50% chance that each child will inherit the mutation and develop the syndrome. However, the severity of symptoms can vary greatly among affected individuals, even within the same family. In some cases, a new mutation can occur, leading to TDO in an individual without a family history of the disorder. The risk of recurrence for subsequent children depends on whether the mutation was inherited or occurred de novo.