What are the other Names for this Condition? (Also known as/Synonyms)

• Amish Brittle Hair Syndrome
• Brittle Hair-Intellectual Impairment-Decreased Fertility-Short Stature Syndrome
• Tay Syndrome

What is Trichothiodystrophy? (Definition/Background Information)

• Trichothiodystrophy (TTD) is described as a rare group of inherited disorders that are characterized by abnormalities in the skin, hair, nail, and physical and mental health growth. The manifestation of signs and symptoms may be apparent following the birth of the child. TTD is grouped into the photosensitive and non-photosensitive subtypes
• The cause of Trichothiodystrophy is due to genetic mutations that are passed down through families in an autosomal recessive manner. TTD may result in rough-scaly skin, photosensitivity, short brittle hair, cataracts, apart from growth delays and cognitive impairment
• Trichothiodystrophy can neither be prevented nor cured, but may be adequately managed through topical agents, sun protection measures, use of visual aids, nutritional and growth support, and occupational therapy. The outcomes depend on the severity of the disorder, which may vary from one individual to another

Who gets Trichothiodystrophy? (Age and Sex Distribution)

• Trichothiodystrophy is a very rare inherited disorder, with only about 100 cases reported worldwide in the scientific literature
• It is a congenital disorder, and the onset of symptoms may occur at birth or in infancy
• Both genders may be affected by this disorder
• Individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Trichothiodystrophy? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Trichothiodystrophy (TTD).

• A positive family history may be an important risk factor, since TTD can be inherited in some cases
• Children born to consanguineous parents may bear a higher risk of this disorder 

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Trichothiodystrophy? (Etiology)

Trichothiodystrophy may be caused by mutation(s) in the ERCC2, ERCC3, or GTF2H5 genes. In some cases, the condition is inherited in an autosomal recessive manner.

• The proteins coded for by these genes are members of the transcription factor IIH complex, crucial to DNA repair and initiation of protein synthesis
• Therefore, mutation(s) in these genes hampers both DNA repair and protein synthesis causing photosensitivity (among other symptoms) in the affected individuals
• In addition to the three genes mentioned-above, mutation(s) in the MPLKIP gene may also cause the non-photosensitive form of Trichothiodystrophy

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Trichothiodystrophy?

The signs and symptoms of Trichothiodystrophy may vary among affected individuals in type and severity. Whereas some of those affected may only exhibit mild symptoms limited to abnormalities in the hair, others may experience additional and severe symptoms.

The signs and symptoms of Trichothiodystrophy may include:

• Sensitivity to sunlight
• Sparsely distributed hair; brittle hair
• Rough and dry skin (scaly appearance)
• Abnormal nails
• Growth retardation 
• Intellectual deficiency
• Cataracts at birth
• Skeletal abnormalities

How is Trichothiodystrophy Diagnosed?

Trichothiodystrophy is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms, including eye exams and skeletal structure evaluation
• Laboratory tests, as needed
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Scanning electron microscopy to check for the presence of defects in the hair cuticles
• Biopsy studies, if necessary
• Molecular genetic testing to check for, or confirm the causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Trichothiodystrophy?

The complications of Trichothiodystrophy may include:

• Emotional stress due to cosmetic concerns
• Severe sunburns
• Delayed growth
• Decreased fertility
• Impaired vision due to congenital cataracts
• Severe intellectual deficiency
• Recurrent infections that may include life-threatening respiratory infections

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Trichothiodystrophy Treated?

Currently, there is no cure for Trichothiodystrophy since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment measures may include:

• Topical applications and emollients for dry rough skin
• For skin protection: Use of sunscreens with high SPF (sun protection factor), UV-protected sunglasses, and suitable protective clothing including wide-brimmed hats
• Visual aids to help low or poor vision and surgical removal of cataracts, as needed
• Nutritional support including growth hormone therapy
• Physical and occupational therapy

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

How can Trichothiodystrophy be Prevented?

Trichothiodystrophy may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

In some cases, the condition may be familial, meaning they occur within families. In expecting parents with a familial history:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Trichothiodystrophy? (Outcomes/Resolutions)

The prognosis of Trichothiodystrophy is dependent upon the severity of the signs and symptoms and associated complications, if any noted.

• Providing adequate treatment and support to children with mild/moderate conditions can ensure optimal outcomes
• However, individuals with severe signs and symptoms have been reported to succumb to the condition in childhood

Additional and Relevant Useful Information for Trichothiodystrophy:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/