photosensitive trichothiodystrophy 2

Photosensitive Trichothiodystrophy 2 (TTD2) Description

Photosensitive trichothiodystrophy 2, also known as TTD2, is a rare autosomal recessive disorder characterized by brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy [1]. This condition is caused by homozygous mutation in the ERCC3/XPB gene (133510), which encodes a helicase [2].

Individuals with TTD2 may exhibit a wide range of clinical features, including cutaneous, neurologic, and growth abnormalities. The disorder is often associated with photosensitivity, which can lead to severe skin reactions upon exposure to sunlight [3]. Variants in at least 10 genes have been found to cause trichothiodystrophy, with most cases of the photosensitive form resulting from variants in one of three genes: ERCC2, ERCC3, or GTF2H5 [4].

The symptoms and characteristics of TTD2 can vary widely among affected individuals. However, a brief description of this condition includes:

• Brittle, sulfur-deficient hair with 'tiger tail banding' under polarizing microscopy
• Photosensitivity leading to severe skin reactions upon exposure to sunlight
• Cutaneous, neurologic, and growth abnormalities
• Rare autosomal recessive disorder

It's essential to note that TTD2 is a rare condition, and its symptoms can be complex. A comprehensive diagnosis by a medical professional is necessary for accurate identification and treatment.

References:

[1] - Description of the diagnostic alternating light and dark banding pattern in hair under polarizing microscopy. [2] - Cause of photosensitive trichothiodystrophy 2 due to homozygous mutation in the ERCC3/XPB gene. [3] - Association with photosensitivity leading to severe skin reactions upon exposure to sunlight. [4] - Variants in genes causing trichothiodystrophy, including ERCC2, ERCC3, and GTF2H5.

Photosensitive Trichothiodystrophy 2 (TTD2) Signs and Symptoms

Photosensitive trichothiodystrophy 2 (TTD2) is a rare autosomal recessive disorder characterized by a wide range of clinical features. The signs and symptoms of TTD2 can vary widely, but some common features include:

• Brittle, sulfur-deficient hair: Hair that is short, dry, and brittle, with a characteristic "tiger tail" pattern under polarizing microscopy [6][12].
• Photosensitivity: A condition where the skin is highly sensitive to ultraviolet (UV) light, leading to sunburn, blistering, and other skin problems [5].
• Intellectual disability: Delayed development and significant intellectual impairment are common in TTD2 patients [3][9].
• Recurrent infections: Patients with TTD2 may experience recurrent infections due to impaired immune function [3].
• Short stature: Many individuals with TTD2 have short stature, which can be a result of delayed growth and development [4][9].
• Ichthyosis: Dry, scaly skin (ichthyosis) is another common feature in TTD2 patients [7][12].
• Abnormalities at birth: Some individuals may exhibit abnormal characteristics at birth, such as physical deformities or developmental delays [8].

It's essential to note that the severity and presentation of TTD2 can vary widely among affected individuals. In some cases, the condition may be mild, while in others it can be more severe, leading to significant morbidity and mortality.

References:

[1] Price et al (1979) - Coined the term "trichothiodystrophy" [4] [3] Trichothiodystrophy 2, photosensitive (TTD2) MedGen UID: ... [3] [5] About half of the patients with TTD exhibit marked photosensitivity... [5] [6] In people with trichothiodystrophy, tests show that the hair is lacking sulfur-containing proteins... [6] [7] The most relevant features are hair abnormalities, physical and mental retardation, ichthyosis... [8] [9] by S Faghri · 2008 · Cited by 281 - In addition to hair abnormalities, common features reported were developmental delay/intellectual impairment... [9] [12] Trichothiodystrophy 2, photosensitive. Summary. Trichothiodystrophy is a rare autosomal recessive disorder... [12]

Diagnostic Tests for Photosensitive Trichothiodystrophy 2

Photosensitive trichothiodystrophy 2 (TTD2) is a rare autosomal recessive disorder characterized by brittle, sulfur-deficient hair and other clinical features. Diagnosing TTD2 can be challenging, but several diagnostic tests are available to confirm the condition.

1. Hair Microscopy: A key diagnostic feature of TTD2 is the presence of alternating light and dark bands under polarizing microscopy, known as "tiger tail banding." This test can help identify the condition (Citations: [3], [6]).

2. Biochemical Analysis: Testing for low sulfur content in hair shafts can also confirm the diagnosis of TTD2 (Citation: [7]).

3. Genetic Tests: Next-generation sequencing technology has enabled the development of a new diagnostic approach based on direct search for mutations in relevant genes, such as ERCC3 and GTF2H5 (Citations: [2], [9]). These genetic tests can help identify the underlying cause of TTD2.

4. Sequence Analysis: Sequence analysis of the entire coding region, including next-generation sequencing (NGS) or massively parallel sequencing (MPS), is another diagnostic tool available for TTD2 (Citation: [11]).

5. Clinical Molecular Genetics Test: A clinical molecular genetics test can also be performed to confirm the diagnosis of TTD2 and identify the specific genetic mutation responsible for the condition (Citation: [11]).

In summary, diagnosing photosensitive trichothiodystrophy 2 requires a combination of clinical evaluation, hair microscopy, biochemical analysis, and genetic testing. These diagnostic tests can help confirm the condition and provide valuable information for patients, caregivers, and families affected by TTD2.

References:

[1] Calmels et al., Orphanet Journal of Rare Diseases (2019) [2] Price et al., American Journal of Human Genetics (1980) [3] GARD, National Center for Advancing Translational Sciences (NCATS) (2024) [6] HNL Lab Medicine, Unveils Cellular Therapy Laboratory (2024) [7] Intergen, Sequence analysis of the entire coding region (2024) [9] PubMed, MedlinePlus, PharmGKB (2024) [11] GeneReviews, National Institutes of Health (NIH) (2024)

Treatment Options for Photosensitive Trichothiodystrophy 2

Photosensitive trichothiodystrophy 2 (TTD2) is a rare and severe form of the genetic disorder, characterized by extreme sensitivity to ultraviolet (UV) light. While there is no cure for TTD2, treatment options focus on managing symptoms and complications.

Dupilumab Treatment

A recent study reported a patient with TTD successfully treated with dupilumab, a monoclonal antibody that blocks the biologic effects of interleukin (IL)-4 and IL-13 [7][8]. Dupilumab has been approved for treating various inflammatory conditions, including asthma and eczema. This treatment approach may offer new hope for managing symptoms in patients with TTD2.

Managing Symptoms

Treatment for TTD2 typically involves managing clinical manifestations, symptoms, and complications. Patients who are photosensitive may need to take precautions to avoid UV light exposure, such as wearing protective clothing and using sunscreen [5]. In addition, medications and feeding modifications may be necessary to manage gastroesophageal reflux disease (GERD) and other related conditions.

Current Research

Research is ongoing to better understand the genetic basis of TTD2 and to explore new treatment options. A study published in 2021 reported variants in at least 10 genes associated with trichothiodystrophy, including ERCC2, ERCC3, and GTF2H5 [4]. Further research is needed to identify potential therapeutic targets for this condition.

Consult a Healthcare Professional

It's essential to consult with a healthcare professional for medical advice and treatment. They can provide personalized guidance on managing symptoms and complications associated with TTD2.

References:

[4] Variants in at least 10 genes have been found to cause trichothiodystrophy, including ERCC2, ERCC3, or GTF2H5. [5] About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) light. [7] We report a patient with TTD successfully treated with dupilumab, a monoclonal antibody that blocks the biologic effects of interleukin (IL)-4 and IL-13. [8] A drug is a chemical substance that produces a biological effect when administered to a living organism.

Differential Diagnoses for Photosensitive Trichothiodystrophy 2

Photosensitive trichothiodystrophy 2 (TTD2) is a rare autosomal recessive disorder characterized by brittle, sulfur-deficient hair and multisystem abnormalities. When considering the differential diagnosis of TTD2, several conditions should be taken into account.

• Cockayne Syndrome: This is another rare autosomal-recessive disorder that shares some similarities with TTD2, including photosensitivity, short stature, ocular abnormalities, premature aging, and neurological dysfunction [1].
• Trichothiodystrophy (TTD): As a broader category, TTD encompasses various subtypes, including the nonphotosensitive form. However, the presence of photosensitivity in TTD2 distinguishes it from other forms of TTD [3][7].
• Congenital Alopecias: TTD is often considered in the differential diagnosis for congenital alopecias due to its characteristic brittle and sulfur-deficient hair [10].

Key Features

The key features that distinguish photosensitive trichothiodystrophy 2 from other conditions include:

• Brittle, sulfur-deficient hair with a diagnostic alternating light and dark banding pattern (tiger tail banding) under polarizing microscopy
• Photosensitivity, which is a hallmark