nonphotosensitive trichothiodystrophy

Nonphotosensitive Trichothiodystrophy (TTD): A Rare Inherited Condition

Nonphotosensitive trichothiodystrophy, commonly referred to as TTD, is a rare inherited condition that affects various parts of the body. This autosomal recessive disorder is characterized by brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern under polarizing microscopy, known as "tiger tail banding" [3][5].

Clinical Features

Individuals with nonphotosensitive trichothiodystrophy may exhibit a wide range of clinical features, including:

• Brittle, sulfur-deficient hair
• Sparse hair growth
• Cutaneous abnormalities (e.g., scaly skin)
• Neurological issues (e.g., failure to thrive, microcephaly, neuromotor developmental delay)
• Growth deficiencies

Genetic Causes

While the genetic cause of nonphotosensitive trichothiodystrophy is unknown in some cases [1], research suggests that mutations in genes involved in RNA repair and protein production may contribute to this condition [4]. In contrast to photosensitive TTD, which is often caused by mutations in DNA repair genes such as ERCC2 (XPD) or MPLKIP (TTDN1), nonphotosensitive TTD has been linked to mutations in other genes, including MPLKIP (TTDN1) [7].

Phenotypic Spectrum

The phenotypic spectrum of nonphotosensitive trichothiodystrophy is diverse and can vary significantly among affected individuals. Some cases may present with more severe symptoms, such as failure to thrive, microcephaly, and neuromotor developmental delay, while others may exhibit milder features [11][13].

References

[1] Faghri et al., 2008 [3] Pascolini et al., 2020 [4] Botta et al., 2021 [5] Mendelsohn et al., 2020 [7] Giulia Pascolini, Corresponding Author.

Nonphotosensitive Trichothiodystrophy Signs and Symptoms

Nonphotosensitive trichothiodystrophy (TTD) is a rare genetic disorder characterized by a range of symptoms. While the severity and presentation can vary widely, some common signs and symptoms include:

• Brittle hair: One of the hallmark features of TTD is brittle, fragile hair that breaks easily.
• Scaly skin:

Based on the provided context, diagnostic tests for nonphotosensitive trichothiodystrophy (TTD) include:

• Biochemical analysis of hair shafts to demonstrate low sulfur content [4]
• Deletion/duplication analysis [5]
• Microsatellite instability testing (MSI) [5]
• Mutation scanning of select exons [5]

Additionally, the following tests may be used to support a diagnosis of nonphotosensitive TTD:

• Polarizing microscopy of hair shafts to observe tiger-tail-pattern hair or other characteristic banding patterns [6][7][8]
• Clinical evaluation for symptoms such as brittle hair, mental and growth retardation, typical facies, and ichthyosis [8]

It's worth noting that the diagnosis of nonphotosensitive TTD is often made based on a combination of these tests, rather than a single test. A primary care provider or genetic specialist may be able to help determine the best course of testing for an individual case.

References:

[4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8

Treatment Options for Nonphotosensitive Trichothiodystrophy

Nonphotosensitive trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by neuroectodermal symptoms, including sulfur-deficient brittle hair, dystrophic nails, ichthyosiform erythroderma, growth retardation, intellectual impairment, and recurrent infections. While there is no cure for TTD, various treatment options are available to manage its clinical manifestations.

Symptomatic Treatment

Treatment for nonphotosensitive TTD is primarily symptomatic and focused on managing the disease's complications. Patients may require regular follow-ups with a multidisciplinary team involving dermatologists, pediatricians, ophthalmologists, and other specialists (1). The goal of treatment is to precociously detect any neurological, skin, growth delay, malformation, and/or immune deficiency.

Management of Clinical Manifestations

Given the absence of a cure for TTD, management focuses on treating individual symptoms. For example:

• Brittle hair: Treatment may involve topical creams or ointments to moisturize and protect the hair (2).
• Skin manifestations: Patients with ichthyosiform erythroderma may benefit from topical treatments, such as emollients and keratolytics (3).
• Growth retardation: Hormone replacement therapy may be necessary to address growth delays (4).

Emerging Therapies

Recent studies have explored the use of dupilumab, a monoclonal antibody targeting IL-4Rα, in treating TTD. A case report published in 2021 described successful treatment of a patient with nonphotosensitive TTD using dupilumab (5). This emerging therapy may offer new hope for patients with this condition.

References

• [1] Knowledge on rare diseases and orphan drugs ... Trichothiodystrophy
• [2] Treatment Options. Treatment options are summarized in Table I.
• [3] Successful treatment of trichothiodystrophy with dupilumab Clin Exp Dermatol. 2021 Oct;46(7):1381-1383. doi: 10.1111/ced.14642.
• [4] Trichothiodystrophy Syndromes / drug therapy*
• [5] Xiaolong, Z, Khan, S, Tamura, D, Patronas, N, Zein, W, Brooks, B. “Brittle hair, developmental delay ...