Trichothiodystrophy (TTD)
Description
Trichothiodystrophy (TTD) is a rare genetic disorder that primarily affects the hair, skin, and nails. Individuals with TTD often have brittle hair that breaks easily, a characteristic known as ‘trichorrhexis invaginata.‘ This condition is also associated with other symptoms such as skin abnormalities, intellectual disabilities, and increased risk of certain cancers. TTD is caused by mutations in genes involved in DNA repair, leading to instability in the genetic code. While there is no cure for TTD, management strategies focus on addressing the specific symptoms and preventing complications. This blog provides a comprehensive overview of TTD, covering its signs and symptoms, causes, diagnosis, management, and the genes involved.
Genes Involved
Genes Involved in Trichothiodystrophy (TTD)
TTD is caused by mutations in genes involved in DNA repair. DNA repair is essential for maintaining the integrity of the genome, and defects in this process can lead to a range of genetic disorders. Some of the genes implicated in TTD include:
- ERCC2 (XPD): This gene is involved in the nucleotide excision repair (NER) pathway, which removes damaged DNA segments.
- ERCC3 (XPB): Another gene involved in the NER pathway, ERCC3 works with ERCC2 to remove damaged DNA.
- ERCC8 (CSA): This gene is part of the transcription-coupled repair (TCR) pathway, a specialized sub-pathway of NER. TCR removes lesions from actively transcribed genes.
- ERCC5 (CSB): Similar to ERCC8, this gene plays a role in TCR and is crucial for repairing DNA damage in actively transcribed genes.
- XPG: This gene is involved in the later stages of NER, where it cuts out the damaged DNA segment.
- TTD-A (TTDA): This gene, also known as the TTD-associated gene, is involved in the repair of double-strand DNA breaks, a more severe type of DNA damage.
Recognizing the Signs and Symptoms
Recognizing the Signs and Symptoms of Trichothiodystrophy (TTD)
The most distinctive feature of TTD is brittle hair, which is often described as ‘hair that breaks easily.‘ This characteristic, known as ‘trichorrhexis invaginata,‘ is often present from birth. Other common signs and symptoms include:
- Skin abnormalities: TTD can cause dry, scaly skin, increased sensitivity to sunlight, and a predisposition to skin cancer. Some individuals may also have ichthyosis, a condition that causes thick, scaly skin.
- Nail abnormalities: Brittle nails are a common feature of TTD. The nails may also be thin, ridged, or discolored.
- Intellectual disability: Some individuals with TTD have intellectual disability, ranging from mild to severe.
- Neurological problems: TTD can also cause neurological problems, including seizures, developmental delays, and movement disorders.
- Increased risk of cancer: People with TTD have an increased risk of certain types of cancer, particularly skin cancer.
Causes
Causes of Trichothiodystrophy (TTD)
TTD is caused by mutations in genes involved in DNA repair. These mutations prevent the body from effectively repairing damaged DNA, leading to the accumulation of DNA errors. This genetic instability can manifest in various ways, leading to the characteristic symptoms of TTD. The specific gene mutation and the severity of the mutation can influence the severity of symptoms.
Inheritance/recurrence risk
Inheritance and Recurrence Risk of Trichothiodystrophy (TTD)
TTD is usually inherited in an autosomal recessive manner. This means that a person needs to inherit two copies of the mutated gene, one from each parent, to develop the disorder. If both parents carry a mutated gene, there is a 25% chance that their child will inherit two copies and develop TTD. They have a 50% chance of inheriting one copy and being a carrier, and a 25% chance of not inheriting the mutated gene at all.
While TTD is often inherited, sporadic cases can occur when a new mutation arises in the gene responsible. This means that the individual may not have any family history of the condition.
