Trichothiodystrophy

What is trichothiodystrophy?

Trichothiodystrophy is a rare, multisystem, autosomal recessive disorder characterized by sulfur deficiency, short, brittle hair. Other clinical features may include photosensitivity, ichthyosis, intellectual disability, hematological abnormalities, decreased fertility, and short stature [1].

The name trichothiodystrophy was coined by Price et al in 1979, and is derived from the Greek: tricho (hair), tio (sulfur), dys (defective), trophy (feeding).

Trichothiodystrophy is classified into photosensitive and non-photosensitive subtypes [2].

Who gets trichothiodystrophy?

The estimate incidence of trichothiodystrophy is one per million live births. Men and women are equally affected. Trichothiodystrophy has been described in several ethnic groups throughout the world, although it occurs more commonly among populations where consanguinity it is common [1,3].

What Causes Trichothiodystrophy?

Trichothiodystrophy is caused by defects DNA repair and transcription and is inherited in a autosomal recessive pattern, which means that both parents must have the mutated gene that causes trichothiodystrophy for the child to inherit.

• Photosensitive trichothiodystrophy generally results from mutations in DNA repair genes ERCC2 (XPD), ERCC3 (XPD) or GTF2H (p8/ /TTDA), with the first (ERCC2 / XPD) gene mutation being more common
• Some cases of non-photosensitive trichothiodystrophy have been associated with mutations in MPLKIP (TTDN1), a gene of unknown function [2–4].

What are the clinical features of trichothiodystrophy?

Trichothiodystrophy is characterized by short, brittle, sulfur-deficient hair, which is sparse and breaks easily. Other clinical features are highly variable in expression. Approximately 50% of patients have associated photosensitivity, although this does not confer an increased risk of skin in the future. Cancer (unlike patients with xeroderma pigmentosa).

Additional cutaneous features may include xerosis, ichthyosis and collodion membrane at birth. It may also be associated with onychodystrophy (fragile nail) [1–3].

Other associated non-dermatologic abnormalities may include:

• Complications related to pregnancy, which occur in about 30% of cases (intrauterine growth retardation, pre-eclampsia and eclampsia, preterm delivery [<37 weeks gestation] and low birth weight)
• Intellectual impairment / developmental delay (85% of cases)
• Short stature (73% of cases)
• Ocular abnormalities including congenital waterfalls, strabismus and nystagmus (approximately 50% of cases)
• Rheumatological abnormalities (joints contractures and dislocations, axial osteosclerosis and distal osteopenia)
• Hematological abnormalities (anemia, neutropeniaand characteristics of β-thalassemia trait)
• Recurrent infections, particularly respiratory, that develop in the first year of life [1,5].

The clinic phenotype Trichothiodystrophy ranges from mild disease with hair abnormalities to severe disease with recurrent infections and severe developmental defects. Various acronyms have been created to describe the different clinical features. phenotypes viewed

• PIBIDS: P (photosensitivity), I (ichthyosis), B (brittle hair), I (intellectual deterioration with low IQ), D (decreased fertility) and S (short stature).
• In non-photosensitive trichothiodystrophy, IBIDS and BIDS represent the initials of the same words. [3].

What are the complications of trichothiodystrophy?

Complications of trichothiodystrophy are primarily related to a high risk of serious and life-threatening infections. [5].

How is trichothiodystrophy diagnosed?

Trichothiodystrophy can be diagnosed by demonstrating a low sulfur content on biochemical analysis of hair shafts, in addition to one of the following findings:

• Trichoschisis (broken or split hairs)
• Alternating light and dark bands or “tiger's tail” bands on the hair shaft, found by polarized light microscopy or trichoscopy
• A severely damaged or missing hair cuticle when scanning electron microscope [3].

Which is the differential diagnosis for trichothiodystrophy?

Differential diagnoses of trichothiodystrophy may include:

Cockayne syndrome

Cockayne syndrome is a rare autosomal recessive DNA repair disorder characterized by photosensitivity, a distinctive facial appearance, short stature, eye abnormalities, premature aging, and neurological dysfunction.

Xeroderma pigmentosum

Xeroderma pigmentosum is a rare autosomal recessive DNA repair condition, characterized by the early development of pigmentary changes, an increased risk of Ultraviolet radiationinduced skin and mucous membrane cancer, severe photosensitivity (50%), and in some individuals, progressive neurodegeneration (30%).

Menkes disease

Menkes disease (also known as Menkes curly hair syndrome) is a congenital disease linked to the X chromosome genetic disorder in which copper deficiency causes peculiar "twisted" (very kinky) hair, neurodegeneration, and connective tissue abnormalities.

Netherton syndrome

Netherton syndrome is a rare autosomal recessive cornification condition characterized by a triad of inflammatory and scaly skin lesions, a characteristic hair shaft abnormality marked as trichorrhexis invaginata ("bamboo hair") and an increased incidence of allergic diseases such as food allergy, urticariaand atopic dermatitis [2,3].

What is the treatment for trichothiodystrophy?

Trichothiodystrophy patients generally have complex health care needs and benefit from a multidisciplinary approach, with input from pediatrics, genetics, ophthalmology, neurology, obstetrics, orthopedics, infectious diseases, dermatologyand radiology. Appropriate genetic counseling should be offered to affected patients and their families.

Since there is no cure for trichothiodystrophy, treatment relies primarily on managing the clinical manifestations, symptoms, and complications. Patients who are photosensitive should be counseled on sun protection. Infections must be treated early and aggressively. [1].

What is the result of trichothiodystrophy?

Since there is no cure for trichothiodystrophy, the forecast it is typically poor for children with serious illness and the average age of death is reported as 3 years. During the neonatal and childhood period, there are substantial morbidity and mortality, with pneumonia and other infections (particularly septicemia) being the main causes of death [1].