Title: Trichothiodystrophy Word Count: 304 Summary: Trichothiodystrophy or TTD, as it is concisely mentioned, is a heterogeneous group of autosomal recessive disorders, characterized by abnormally sulfur deficient brittle hair and accompanied by ichthyosis Keywords: Health Article Body: Trichothiodystrophy or TTD, as it is concisely mentioned, is a heterogeneous group of autosomal recessive disorders, characterized by abnormally sulfur deficient brittle hair and accompanied by ichthyosis and other manifestations. In TTD patients, the hair appear dry, short and sparse, and the ones already existing splits longitudinally in to small fibers, the viscoelastic parameters of hair being compromised compared to controls. Inside the range of TTD syndrome are numerous interrelated neuroectodermal disorders. The Trichothiodystrophy syndromes are invariably characterized by the defective synthesis of high-sulfur matrix proteins. Half of the patients show abnormalities in nucleotide excision repair (NER) of ultraviolet damaged DNA. In fact, three categories are recognized on the basis of cellular responses to UV damage and the affected gene. Most patients show 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 are found to be damaged. Beyond deficiency in the NER pathway, basal transcription is altered leading to decreased transcription of specific genes. TTD patients generally have an unusual facial appearance, marked by protruding ears and receding chin, and retarded overall growth. The growth retardation, neurological abnormalities and brittle hair and nails are attributed to the depressed RNA synthesis in TTD patients. Light microscopy on TTD patients reveals trichosis of hair and an irregular hair surface and diameter. But a nodal appearance and decreased cuticular layer with twisting may be misleading and may closely mimic trichorrhexis nodosa. Also, when the patient’s hair is viewed under polarized light, it shows alternate light and dark bands giving a strand a ‘tiger-tail’ appearance. But it has been noticed recently that such ‘tiger-tail’ patterns are also found in healthy infants. Hence the amino acid analysis quantitating sulfur levels remains a reliable test for TTD.