SNP Shot: Genomic Insights

Trichothiodystrophy (TTD) is a rare, inherited disorder affecting multiple systems in the body. A key characteristic is sparse and fragile hair.

Individuals with TTD have hair deficient in sulfur-containing proteins, which normally provide strength. Microscopic examination of the hair reveals alternating light and dark bands, resembling a "tiger tail" pattern.

The signs and symptoms of TTD vary considerably. Mild cases primarily affect the hair. More severe cases can involve developmental delays, significant intellectual disability, and frequent infections. In the most severe instances, individuals may only survive into infancy or early childhood.

Mothers of children with TTD may experience complications during pregnancy, such as preeclampsia (pregnancy-induced high blood pressure) and HELLP syndrome, which can damage the liver. Infants with TTD are at higher risk for premature birth, low birth weight, and impaired growth. Many children with TTD have short stature.

Intellectual disability and developmental delays are common in TTD, although most affected individuals are very social and engaging. Some individuals with TTD exhibit brain abnormalities detectable through imaging. A frequent neurological feature is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and facilitates rapid nerve impulse transmission.

TTD is also linked to recurrent infections, particularly respiratory infections, which can be life-threatening. Individuals with TTD may have abnormal red blood cells, including smaller-than-normal red blood cells. They may also have elevated levels of hemoglobin A2, a protein found in red blood cells. Other features of TTD can include dry, scaly skin (ichthyosis), nail abnormalities, congenital cataracts (clouding of the lens present at birth), poor coordination, and skeletal abnormalities like early hip degeneration.

Approximately half of individuals with TTD have a photosensitive form, causing extreme sensitivity to ultraviolet (UV) rays from sunlight. They experience severe sunburn after minimal sun exposure. However, they surprisingly do not develop other sun-related issues like excessive freckling or increased skin cancer risk. Many with TTD report an inability to sweat.

Inheritance:

TTD is inherited in an autosomal recessive manner. This means that both copies of the responsible gene must have a variant for the disorder to manifest. Parents of a child with an autosomal recessive condition each carry one copy of the altered gene but typically do not show signs or symptoms of the condition themselves.