Trichothiodystrophy

Trichothiodystrophy is a group of rare, autosomal recessive disorders with brittle, sulphur deficient hair and abnormalities of the skin, nails, nervous system and other organs.

Its frequency is about 1 in a million births. It is divided into photosensitive forms (due to defects in DNA repair genes ERCC2, ERCC3 and GTF2H5) and non-photosensitive forms (MPLKIP, TTDN1, and others, which are less often found).

The abbreviations IBIDS and PIBIDS describe the combination of ichthyosis, brittle hair, intellectual impairment, decreased fertility and short stature, with photosensitivity in the second.

Pathophysiology.

Low content of cysteine rich matrix proteins (high sulphur keratin associated proteins) weakens the hair shaft. In photosensitive forms, the transcription and repair factor TFIIH is unstable, which impairs transcription more than DNA repair, so skin cancer risk is not raised, unlike in xeroderma pigmentosum.

• Brittle, sparse, short hair, with eyebrows and lashes affected, and fragile nails.
• Ichthyosis, collodion baby presentation, photosensitivity (in photosensitive forms), short stature, delayed development, intellectual disability, microcephaly, ataxia, cataracts, dental caries and recurrent infections.
• Pregnancy complications for the mother and low birth weight in the baby are described.

Red flags.

• Neonatal sepsis or recurrent severe infection.
• Cataract in infancy, hearing loss or developmental regression.

• Polarising light microscopy of hair shows a "tiger tail" banding pattern (alternating light and dark bands), which is diagnostic. Hair shaft has trichoschisis (transverse fractures) and low sulphur and cysteine content on amino acid analysis.
• Gene testing (ERCC2, ERCC3, GTF2H5, MPLKIP, TTDN1). DNA repair testing in photosensitive forms.
• Investigations by organ: ophthalmology, audiology, brain MRI, growth, bone age, and immunology if there are infections.

Differential diagnosis.

• Netherton syndrome (trichorrhexis invaginata) and other ichthyoses.
• Xeroderma pigmentosum and Cockayne syndrome (photosensitive repair disorders).
• Monilethrix, pili torti and Menkes disease.

• Multidisciplinary care: dermatology, paediatrics, neurology, ophthalmology, audiology, dentistry and genetics.
• Skin: emollients and keratolytics (urea 10%) for ichthyosis, gentle hair care, and sun protection (SPF 30 or more and clothing) in photosensitive forms.
• Infections need prompt treatment, and growth and nutrition need support. Cataract surgery and hearing aids when needed.
• Genetic counselling (25% recurrence risk) and prenatal diagnosis where the variants are known.
• No treatment cures the disease. Prognosis varies, with early death from infection in severe forms, and a normal life span in mild forms.

Monitoring. Growth, development, eyes and hearing every 6 to 12 months.

Referral and escalation. Genetics and paediatric dermatology; emergency review for fever in infants.