nonphotosensitive trichothiodystrophy 7

Nonphotosensitive trichothiodystrophy-7 (TTD7) is a rare autosomal recessive disorder characterized by cysteine- and threonine-deficient hair that displays a diagnostic alternating light and dark 'tiger-tail' banding pattern under polarization microscopy [1, 3, 5, 10]. This condition is also associated with ichthyosis [1, 3, 10].

The hallmark of TTD7 is the presence of brittle and sulfur-deficient hair that exhibits a unique "tiger tail" pattern under polarized light microscopy. This distinctive feature is a key diagnostic criterion for this condition.

In addition to the characteristic hair abnormalities, individuals with TTD7 may also experience other symptoms, although these are not always present [4, 11]. The oral region has been involved in some cases, with features such as a high-arched palate and a wide mouth being observed [11].

TTD7 is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to express the condition [13]. The genetic basis of TTD7 is not yet fully understood, but it is believed to involve mutations in genes related to nucleotide excision repair (NER) [12].

Overall, nonphotosensitive trichothiodystrophy-7 is a rare and complex disorder that affects multiple aspects of an individual's health.

Nonphotosensitive Trichothiodystrophy (TTD) - Signs and Symptoms

Nonphotosensitive trichothiodystrophy is a rare genetic disorder characterized by a range of symptoms. The signs and symptoms of TTD can vary widely, but some common features include:

• Brittle hair: One of the hallmark features of TTD is brittle hair that breaks easily.
• Mental retardation: Many people with TTD experience intellectual impairment or delayed development.
• Growth retardation: Some individuals with TTD may experience growth delays or failure to thrive.
• Typical facies: People with TTD often have a distinctive facial appearance, although the exact features can vary.
• Ichthyosis: A condition characterized by scaly skin is also common in people with TTD.

In some cases, nonphotosensitive trichothiodystrophy may be associated with additional symptoms such as:

• Brittle nails
• Scaly skin
• Microcephaly (small head size)
• Neuromotor developmental delay

It's worth noting that the severity and range of symptoms can vary widely among individuals with TTD, even within the same family.

Diagnostic Tests for Nonphotosensitive Trichothiodystrophy

Nonphotosensitive trichothiodystrophy, also known as TTD6, is a rare genetic disorder characterized by short, brittle hair and other systemic features. Diagnostic tests are essential to confirm the condition and rule out other possible causes of symptoms.

• Exome-based NextGen sequencing with CNV analysis: This is the favored testing approach for nonphotosensitive trichothiodystrophy (TTD6) [7]. Exome sequencing allows for the simultaneous analysis of all protein-coding genes in a person's genome, making it an effective tool for identifying genetic mutations associated with TTD6.
• Genetic testing: Specific gene mutations, such as those in the GTF2E2 gene, can be identified through genetic testing [9]. This can help confirm the diagnosis and provide information on the underlying cause of symptoms.

Other Diagnostic Tests

While not specific to nonphotosensitive trichothiodystrophy, other diagnostic tests may also be performed to assess overall health and identify potential complications. These may include:

• Baseline evaluation: A comprehensive assessment that includes measurement of growth, developmental assessment, dental evaluation, dermatologic, ophthalmologic, and audiologic evaluations, as well as brain imaging studies [8].
• Cellular tests: Although not available for nonphotosensitive TTD, cellular tests may be used to assess the presence of inactivating mutations in other genes associated with photosensitive forms of trichothiodystrophy.

References

[7] Context 7: Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. [8] Context 8: Baseline evaluation includes measurement of growth, developmental assessment, dental evaluation, dermatologic, ophthalmologic and audiologic evaluations, brain ... [9] Context 9: No cellular tests are available for the non-photosensitive form of TTD. The presence of inactivating mutations in the TTDN1, RNF113A and GTF2E2 genes may ...

Treatment Options for Nonphotosensitive Trichothiodystrophy

Nonphotosensitive trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by brittle hair and intellectual impairment. While there is no cure for TTD, treatment options are available to manage clinical manifestations, symptoms, and complications.

• Multidisciplinary Team Approach: Patients with nonphotosensitive TTD should receive regular follow-ups from a multidisciplinary team involving dermatologists, pediatricians, ophthalmologists, and other specialists to precociously detect any neurological, skin, growth delay, malformation, and/or immune deficiency.
• Symptomatic Treatment: Management of TTD requires symptomatic treatment, which may include:
  • Skin care: Patients with ichthyosiform erythroderma may benefit from topical treatments such as moisturizers and emollients to manage dry skin.
  • Hair care: Brittle hair can be managed with gentle hair care products and avoiding harsh chemicals.
  • Neurological support: Intellectual impairment and developmental delay may require specialized educational and therapeutic interventions.

Recent Advances in Treatment

A recent study reported successful treatment of a TTD case using dupilumab, a monoclonal antibody targeting IL-4Rα [8]. The patient, a 7-year-old boy, exhibited significant improvement in skin symptoms. However, it is essential to note that this treatment option may not be suitable for all patients with nonphotosensitive TTD.

References

• [1] There is currently no cure for TTD. Management of TTD requires participation of many specialists such as dermatologists, pediatricians, ophthalmologists, ...
• [4] Knowledge on rare diseases and orphan drugs ... Trichothiodystrophy. Suggest an update ... There is no specific treatment. Patients should receive regular follow-ups in order to precociously detect any neurological, skin, growth delay, malformation, and/or immune deficiency.
• [8] Successful treatment of trichothiodystrophy with dupilumab Clin Exp Dermatol. 2021 Oct;46(7):1381-1383. doi: 10.1111/ced.14642. ... Trichothiodystrophy Syndromes / drug therapy* Substances Antibodies, Monoclonal, Humanized Interleukin-4 Receptor alpha Subunit

Non-Photosensitive Trichothiodystrophy (TTD) Differential Diagnosis

Trichothiodystrophy (TTD), a rare autosomal recessive disorder, has several differential diagnoses, including:

• Cockayne syndrome: A genetic disorder characterized by photosensitivity, premature aging, and neurological dysfunction.
• Congenital alopecias: A group of conditions characterized by hair loss present at birth.

Key Features of Non-Photosensitive TTD

The main diagnostic criteria for non-photosensitive TTD include:

• Brittle hair: Short, dry, and sulfur-deficient hair with a characteristic "tiger tail" pattern under polarizing microscopy.
• Mental and growth retardation: Delayed physical and mental development.
• Typical facies: A distinctive facial appearance.
• Ichthyosis: Dry, scaly skin.

Other Features

Additional features of non-photosensitive TTD may include:

• Abnormalities of the fingernails and toenails
• Clouding of the lens in both eyes

These characteristics are essential for differential diagnosis and can help distinguish non-photosensitive TTD from other conditions. [6][7][8]

Genetic Basis

Variants in at least seven genes have been reported to cause non-photosensitive forms of trichothiodystrophy, including the MPLKIP gene. [9]