Trichothiodystrophy - Photosensitivity and More

Introduction

Trichothiodystrophy (TTD) is characterized by multiple system involvement and a broad spectrum of abnormalities. It is a rare inherited disorder (autosomal recessive) in which the affected individuals have sulfur-deficient sparse hairs, physical and mental retardation, and recurrent infections. Nearly half of the patients with trichothiodystrophy (TTD) have photosensitivity and extreme sensitivity to ultraviolet (UV) rays. Affected individuals with trichothiodystrophy (TTD) show various signs and symptoms. Mild cases of trichothiodystrophy (TTD) involve the hair, and in severe cases, there will be an intellectual disability, delayed development, and recurrent infections.

What Is Trichothiodystrophy?

Trichothiodystrophy (TTD) is an inherited disorder with a broad spectrum of abnormalities. The affected individuals show a common feature of short, sulfur-deficient, brittle, and dry hair with a microscopic tiger tail pattern. The signs and symptoms associated with trichothiodystrophy (TTD) may differ for different patients. Pregnancy complications are common in affected women and result in low birth weight and pre-term delivery. Infants with trichothiodystrophy may have a shiny covering on the skin that peels off within a week. During childhood, there will be an intellectual disability, developmental delay, scaly skin, short stature, dry skin, bone abnormalities, poor weight gain, recurrent infections, and eye abnormalities (congenital cataracts). Some patients with trichothiodystrophy may have immune system defects leading to recurrent infections like gastroenteritis and pneumonia. Due to multiple complications and infections, patients with trichothiodystrophy (TTD) have an increased risk of death before ten years of age. Based on the presence or absence of photosensitivity, trichothiodystrophy can be photosensitive and non-photosensitive trichothiodystrophy.

What Are the Causes of Trichothiodystrophy?

• Photosensitive Trichothioddystrophy - A genetic mutation is the most common cause of trichothiodystrophy (TTD). Photosensitive trichothiodystrophy occurs due to mutations involving the ERCC2, GTF2H5, or ERCC3 genes. These genes produce a group of proteins, the general transcription factor IIH complex (TFIIH). This protein complex is involved in DNA damage repair caused by ultraviolet radiation from the sun. They are also a part of the steps involved in protein production. Mutations in the ERCC3, ERCC2, and GTF2H5 genes reduce the production of general transcription factor IIH complex (TFIIH) within the cells and disrupt transcription and DNA repair. Thus, the ability to repair DNA damage is reduced, resulting in the sensitivity of body tissues to radiation from the sun (ultraviolet rays).

• Non-photosensitive Tricothiodystrophy - Mutations in the MPLKIP gene cause non-photosensitive trichothiodystrophy. These gene mutations cause trichothiodystrophy in 20 percent of the cases.

What Are the Symptoms of Trichothiodystrophy?

• Neurological Effects - Most affected individuals with trichothiodystrophy (TTD) show delayed developmental milestones. Small-sized head (microcephaly) is common in children and adults with trichothiodystrophy (TTD). Some children may have abnormal levels of myelin in the brain cells and central nervous system. Other symptoms include hearing loss, tremors, reduced muscle coordination, and seizures.

• Ocular Effects - Patients with trichothiodystrophy may have multiple ocular (eye) abnormalities. Some patients have ocular defects at birth; others develop later in childhood. The most common ocular defects in trichothiodystrophy (TTD) are nystagmus (uncontrolled eye movements that affect depth perception and vision) and congenital cataracts. Other ocular abnormalities are small eyeballs, small corneas, dry eyes, and decreased vision.

• Dental and Skeletal Defects - Tricothiodystrophy patients may have skeletal defects like osteosclerosis in the pelvis, skull, and spine. Some patients show thinner peripheral bones of the feet, hands, and lower arms. Dental findings in trichothiodystrophy are thin tooth enamel and recurrent caries. Affected children need special dental care during tooth fillings and extractions.

• Newborn Symptoms - Trichothiodystrophy infants usually have a low birth weight and skin defects. Other symptoms like feeding difficulties, gastrointestinal reflux, chronic itching, dry and thickened skin, and eczema are also seen in trichothiodystrophy infants.

• Pregnancy Symptoms - Maternal complications such as premature labor, pre-eclampsia, placental abnormalities, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) are seen in nearly 81 percent of trichothiodystrophy pregnancies.

• Growth Effects - Trichothiodystrophy children have delayed growth, short stature, and poor weight gain.

• Immune Effects - Individuals with trichothiodystrophy develop recurrent respiratory and gastrointestinal tract infections. Affected children may have reduced neutrophils, immunoglobulin G, and iron levels, resulting in a reduced immune response.

How Can We Diagnose Trichothiodystrophy?

Diagnosis of trichothiodystrophy includes detailed medical history, physical examination, and assessment of specific clinical features. It includes assessment of hair defects, small chin, short stature, developmental delay, ichthyosis, and teeth anomalies. Magnetic resonance imaging (MRI) of the brain can be done to determine abnormal myelination patterns. Other tests like blood count, immune function tests, and iron levels can also be done to diagnose trichothiodystrophy. Trichithiodystrphy (TTD) can be specifically diagnosed using polarized light microscopic examination of hair shafts. It shows a specific tiger tail pattern due to reduced hair sulfur. Other than this, genetic testing can also be done to diagnose trichothiodystrophy (TTD).

What Are the Treatment Options for Trichothiodystrophy?

Treatment options for trichothiodystrophy include a multidisciplinary approach and medical management for multiple symptoms. It includes the following.

• Trichothiodystrophy patients with photosensitivity must be protected from sun exposure.

• Developmental delays in children are identified at an early stage, and special education services must be provided in the schools.

• Physical therapy can be done to overcome poor muscle coordination, joint stiffness, and muscle tightening.

• Dry skin and other skin problems can be managed with softening agents and products with alpha-hydroxy acids.

• Prophylactic antibiotics and immunoglobulins can be used in trichothiodystrophy patients to prevent recurrent infections.

• Genetic counseling is given to families of children with trichothiodystrophy.

Conclusion

Trichothiodystrophy (TTD) is a rare inherited multisystem disorder due to genetic mutations involving ERCC2, GTF2H5, and MPLKIP. The most common clinical symptoms of trichothiodystrophy are sulfur-deficient sparse hairs, physical and mental retardation, photosensitivity, and recurrent infections. In trichothiodystrophy, the sulfur-deficient short, brittle hairs show specific tiger tail patterns when viewed under a polarized light microscope. Management of trichothiodystrophy patients involves multiple strategies to manage different clinical symptoms.