nonphotosensitive trichothiodystrophy 6

Nonphotosensitive trichothiodystrophy (TTD) is a rare genetic disorder that affects the hair, skin, and other parts of the body.

Characteristics of Nonphotosensitive Trichothiodystrophy 6:

• Hair: The hallmark of this condition is hair that is sparse, brittle, and easily broken. The hair may also display a diagnostic 'tiger-tail' banding pattern due to cysteine- and threonine-deficient hair.
• Inheritance: Nonphotosensitive trichothiodystrophy 6 (TTD6) is an autosomal recessive disorder, meaning that it is inherited in a recessive pattern. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Other Features:

• The condition may also be associated with other systemic features, although these are not always present.
• Some forms of nonphotosensitive trichothiodystrophy are caused by variants in genes that are involved in RNA repair and protein production.

References:

• [4] Trichothiodystrophy is a rare, multisystem, autosomal-recessive disorder characterised by sulphur-deficient, short, brittle hair.
• [7] Trichothiodystrophy 7, nonphotosensitive is an autosomal recessive disorder characterized by cysteine- and threonine-deficient hair with a 'tiger-tail' banding pattern.
• [8] Nonphotosensitive trichothiodystrophy-7 (TTD7) is an autosomal recessive disorder characterized by cysteine- and threonine-deficient hair.

Signs and Symptoms of Nonphotosensitive Trichothiodystrophy

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

• Brittle hair: One of the hallmark features of nonphotosensitive trichothiodystrophy is brittle hair that breaks easily.
• Scaly skin: Many people with this condition develop scaly skin, which can be itchy and uncomfortable.
• Failure to thrive: Children with nonphotosensitive trichothiodystrophy may experience failure to thrive, meaning they don't gain weight or grow at a normal rate.
• Microcephaly: Some individuals with this condition may have microcephaly, a condition where the head is smaller than average.
• Neuromotor developmental delay: Nonphotosensitive trichothiodystrophy can also cause delays in neuromotor development, which can affect coordination and balance.

These symptoms can vary widely from person to person, and some individuals may experience only mild symptoms while others may have more severe manifestations. [6][8][9]

References:

• [6] Nonphotosensitive trichothiodystrophy-8 (TTD8) is characterized by brittle hair and nails and scaly skin, accompanied by failure to thrive, microcephaly, and neuromotor developmental delay.
• [8] The main diagnostic criteria of TTD are brittle hair, mental and growth retardation, typical facies, and ichthyosis. The hair abnormalities are considered the hallmark feature of this condition.
• [9] Nonphotosensitive trichothiodystrophy-9 (TTD9) is characterized by brittle hair and nails and scaly skin, accompanied by failure to thrive, microcephaly, ...

Diagnostic Tests for Nonphotosensitive Trichothiodystrophy 6 (TTD6)

Nonphotosensitive trichothiodystrophy 6 (TTD6) is a rare genetic disorder characterized by short, brittle hair and other systemic features. While there are no specific cellular tests available for TTD6, several diagnostic approaches can help confirm the condition.

• Exome-based NextGen sequencing with CNV analysis: This is considered a cost-effective approach to diagnose TTD6, as it allows for reflexing to other exome-based tests if necessary (7).
• Baseline evaluation: A comprehensive baseline evaluation includes measurement of growth, developmental assessment, dental evaluation, dermatologic, ophthalmologic, and audiologic evaluations, brain imaging studies, and other assessments to rule out other conditions (8).

Genetic Testing

While there are no specific cellular tests available for TTD6, the presence of inactivating mutations in certain genes may be indicative of the condition. These include:

• TTDN1: Inactivating mutations in this gene have been associated with TTD6.
• RNF113A: Mutations in this gene may also contribute to the development of TTD6.
• GTF2E2: This gene is another potential candidate for TTD6, although no cellular tests are available for its nonphotosensitive form (10).

Other Diagnostic Considerations

It's essential to note that TTD6 can be challenging to diagnose due to its similarity to other conditions. A thorough medical history, physical examination, and laboratory testing may be necessary to rule out other potential causes of symptoms.

References:

• [7] Favored testing approach for exome-based NextGen sequencing with CNV analysis.
• [8] Baseline evaluation includes measurement of growth, developmental assessment, dental evaluation, dermatologic, ophthalmologic, and audiologic evaluations, brain imaging studies, and other assessments.
• [10] No cellular tests are available for the non-photosensitive form of TTD.

Differential Diagnosis of Nonphotosensitive Trichothiodystrophy

Nonphotosensitive trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by short, brittle hair and multisystem abnormalities. The differential diagnosis for nonphotosensitive TTD includes:

• Cockayne syndrome: A rare autosomal–recessive disorder of DNA repair that presents with photosensitivity, distinctive facial appearance, short stature, ocular abnormalities, premature aging, and neurological dysfunction [1].
• Other congenital alopecias: Nonphotosensitive TTD can be a differential diagnosis in cases of congenital alopecia, where the hair is short, dry, and brittle [4].

Key Features

The main diagnostic criteria for nonphotosensitive TTD include:

• Brittle hair
• Mental and growth retardation
• Typical facies (distinctive facial appearance)
• Ichthyosis (dry, scaly skin)

These features are considered the hallmark of nonphotosensitive TTD, and a diagnosis can be confirmed by molecular analysis [7].

Genetic Variants

Variants in at least seven genes have been reported to cause non-photosensitive forms of trichothiodystrophy, including variants in the MPLKIP gene [9]. These genetic variants are responsible for the multisystem abnormalities associated with nonphotosensitive TTD.

In conclusion, a differential diagnosis of nonphotosensitive trichothiodystrophy should consider Cockayne syndrome and other congenital alopecias. The key features of nonphotosensitive TTD include brittle hair, mental and growth retardation, typical facies, and ichthyosis, which can be confirmed by molecular analysis.

References:

[1] Context 1 [4] Context 2 [7] Context 7 [9] Context 9