Trichothiodystrophy sun sensitivity

Trichothiodystrophy with sun sensitivity (TTDSS) is a rare, autosomal recessive genetic disorder characterized by brittle hair, intellectual impairment, physical and developmental delays, and sensitivity to sunlight. This condition falls under the broader category of Trichothiodystrophy (TTD), which encompasses a group of diseases affecting the sulfur-rich matrix of the hair shaft. The hallmark feature of TTDSS, distinguishing it from other forms of TTD, is the pronounced sensitivity to ultraviolet (UV) light, leading to increased risk of sunburn and potentially skin cancer.

Symptoms and Signs

The primary symptom of TTDSS is brittle, sulfur-deficient hair that has a characteristic tiger-tail pattern under polarized light microscopy. Individuals with TTDSS may also exhibit a range of other symptoms, including:

• Photosensitivity or increased sensitivity to UV light, leading to sunburn and skin damage.
• Intellectual disability, ranging from mild to severe.
• Short stature and skeletal abnormalities.
• Dental anomalies.
• Skin abnormalities, such as ichthyosis, which is a condition characterized by dry, scaly skin.
• Eye abnormalities, including cataracts.
• Increased susceptibility to infections.

Causes

TTDSS is caused by mutations in genes involved in the transcription and repair of DNA, particularly those that encode the subunits of the transcription factor IIH (TFIIH) complex. The most commonly implicated genes include ERCC2 (also known as XPD), ERCC3 (XPB), and GTF2H5 (TTDA). These mutations disrupt the normal function of TFIIH, leading to impaired DNA repair and transcription, which is thought to underlie the diverse symptoms of TTDSS.

Diagnosis

Diagnosis of TTDSS involves a combination of clinical evaluation, microscopic examination of the hair, and genetic testing. The tiger-tail banding pattern of the hair under polarized light microscopy is a key diagnostic feature. Genetic testing can confirm the presence of mutations in the genes associated with TTDSS.

Treatment

There is no cure for TTDSS, and treatment focuses on managing symptoms and preventing complications. Strategies include:

• Avoidance of sun exposure and use of high-SPF sunscreens to protect against UV damage.
• Regular monitoring and treatment of skin, dental, and eye problems.
• Supportive therapies for developmental delays and intellectual disability.
• Nutritional support and physical therapy to address growth and skeletal issues.

Prognosis

The prognosis for individuals with TTDSS varies widely depending on the severity of symptoms. With careful management of photosensitivity and other complications, individuals can lead relatively normal lives. However, the risk of skin cancer and other health issues necessitates ongoing medical supervision.