L12 TRICHOTHIODYSTROPHY: WHERE HAVE WE GONE?
Itin PH
Departments of Dermatology University of Basel and Kantonsspital Aarau, Switzerland

Trichothiodystrophy (TTD) is a heterogeneous group of autosomal recessive disorders with distinctive features of short, brittle hair and abnormally low-sulfur content. The hair of patients with TTD is dry and sparse and the hair shafts break easily with trauma. Fractures of the hair shaft develop, and the viscoelastic parameters of hair are compromised compared to controls. Within the spectrum of the trichothiodystrophy syndromes are numerous interrelated neuroectodermal disorders. The trichothiodystrophy syndromes show defective synthesis of high-sulfur matrix proteins. Abnormalities in nucleotide excision repair (NER) of ultraviolet damaged DNA exist in about half of the patients. Three complementation groups have been characterized among photosensitive patients with trichothiodystrophy. Most patients have mutations on the two alleles of the XPD gene. In UV-sensitive TTD patients the TFIIH transcription factor containing XPB and XPD helicase activities necessary for both transcription initiation and DNA repair is damaged. Beyond deficiency in the NER pathway, basal transcription is altered leading to decreased transcription of specific genes. Depressed RNA synthesis is probably responsible for some clinical features, such as growth retardation, neurological abnormalities and brittle hair and nails. Light microscopy reveals clean transverse fractures through the hair shafts (trichoschisis), and there is an irregular hair surface and diameter. In addition, a decreased cuticular layer with twisting and a nodal appearance may mimic trichorrhexis nodosa. Polarizing microscopy with crossed polarizers shows the typical appearance of alternating light and dark bands, giving a "zigzag" or "tiger-tail" pattern. Within the last few years, it has been shown that "tiger-tail" pattern on polarized hair microscopic examination also may be found in healthy infants, and therefore amino acid analysis quantitating sulfur levels remains the definitive test for TTD. It has been documented alternating dark and white zones within the hair shaft of a young patient who scratched his scalp intensely. The condition appears sufficiently different by polarizing light microscopy, and this sulfur-deficient hair alteration is referred to as "pseudo tiger-tailing". Sperling and DiGiovanna noticed that fibers within the hair shafts of patients with trichothiodystrophy undulate up and down, a feature that is easily observed because of melanin granules embedded in each fiber. The undulations corresponded exactly to the banding seen with polarization. Therefore, the tiger tail phenomenon seen in trichothiodystrophy was interpreted to be caused by a regular undulation of hair fibers within the shafts.