Trichothiodystrophy Q84.2

Davies 1968; Allen 1971; Tay 1971; Price 1980 (naming).

Group autosomal recessive inherited condition with defect in the DNA excision repair system and the essential features of brittle, easily broken, sulfur-deficient hair in a complex combination of variable neuro-ectodermal changes.

Several acronyms are used to describe the clinical manifestations of TTD (see classification below).

Subgroup A: simple trichthiodystrophy.

Subgroup B: Sabinas syndrome (OMIM 211390- named after the Mexican city of Sabinas: short brittle hair, brittle nails, simple trichhiodystrophy, mental developmental disorders)

Subgroup C: Pollitt syndrome (OMIM 275550- named after Pollitt, the first describer: symptoms as in B + folliculitis, kareis, slowed bone development).

Subgroup D: BIDS syndrome (OMIM 234050- brittel hair and nails, developmental delay, short stature, short brittle hair, brittle nails, developmental delay, short stature.

Subgroup E: IBIDS syndrome (OMIM 242170 - brittel hair and nails, developmental delay, short stature, short brittle hair, brittle nails, scaly erythema, progeria, microencephaly, ataxia, lenticular opacities, calcified foci in the brain.

Subgroup E: PIBIDS syndrome (OMIM 278730 - brittel hair and nails, developmental delay, short stature, short brittle hair, brittle nails, scaly erythema, progeria, microencephaly, ataxia, lenticular opacities, calcified foci in the brain + photosensitivity.

TTD can be clinically divided into several types.

To date, several genes have been associated with the pathogenesis of TTD:

• XPB gene
• XPD (mutated in photosensitive TTD) and
• TTDN1 (mutated in non-photosensitive TTD).
• ERCC2 gene (excision repair cross-complementing rodent repair deficiency, complementation group 2). This mutation leads to defects in the DNA excision repair system (Lund EB et al. 2019).

It results in decreased sulfur content of the hair.

Scanning electron microscopy reveals an absence of cuticle. Longitudinal fractures of the hair shaft are evident.

The significance of the sulfur deficiency for the neurological disorders is not clear. There are relationships to xeroderma pigmentosum.

XPB and XPD are genes that also play a role in xeroderma pigmentosum, but unlike xeroderma pigmentosum, TTD is not associated with an increased risk of skin cancer. Clinically, TTD presents with different manifestations, including cutaneous, neurological, and growth abnormalities.

Short brittle hair, trichorrhexis nodosa. Occasionally nail atrophy, koilonychia; congenital ichthyosis, increased photosensitivity, mental retardation, various congenital neuroectodermal disorders, short stature, cataract. The hair shows polarization optically with a succession of dark and light bands (zebra pattern) a typical feature. Increased photosensitivity is not found in all variants of the syndrome. When present, it is associated with disorders of DNA repair (sometimes with xeroderma pigmentosum-likeskin changes).

Patients almost always die early. The average life span is about 10 years.

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