| Synonyms: | Amish brittle hair syndrome, BIDS syndrome, brittle hair–intellectual impairment–decreased fertility–short stature syndrome |
Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into tricho – "hair", thio – "sulphur", and dystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.[1]
Features of TTD can include photosensitivity, ichthyosis, brittle hair and nails, intellectual impairment, decreased fertility and short stature. A more subtle feature associated with this syndrome is a "tiger tail" banding pattern in hair shafts, seen in microscopy under polarized light.[2] The acronyms PIBIDS, IBIDS, BIDS and PBIDS give the initials of the words involved. BIDS syndrome, also called Amish brittle hair brain syndrome and hair-brain syndrome, is an autosomal recessive[3] inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature.[4] There is a photosensitive syndrome, PBIDS.[5]
BIDS is associated with the gene MPLKIP (TTDN1).[6] IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is the Tay syndrome or sulfur-deficient brittle hair syndrome, first described by Tay in 1971.[7] (Chong Hai Tay was the Singaporean doctor who was the first doctor in South East Asia to have a disease named after him.) Tay syndrome should not be confused with the Tay–Sachs disease.[8] [9] It is an autosomal recessive[10] congenital disease.[11] In some cases, it can be diagnosed prenatally.[12] IBIDS syndrome is nonphotosensitive.
The photosensitive form is referred to as PIBIDS, and is associated with ERCC2/XPD and ERCC3.
All photosensitive TTD syndromes have defects in the nucleotide excision repair (NER) pathway, which is a vital DNA repair system that removes many kinds of DNA lesions. This defect is not present in the nonphotosensitive TTD's.[13] These type of defects can result in other rare autosomal recessive diseases like xeroderma pigmentosum and Cockayne syndrome.[14]
Currently, mutations in four genes are recognized as causing the TTD phenotype, namely TTDN1, ERCC3/XPB, ERCC2/XPD and TTDA.[15] Individuals with defects in XPB, XPD and TTDA are photosensitive, whereas those with a defect in TTDN1 are not. The three genes, XPB, XPD and TTDA, encode protein components of the multi-subunit transcription/repair factor IIH (TFIIH). This complex factor is an important decision maker in NER that opens the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a variety of different DNA damages that alter normal base pairing, including both UV-induced damages and bulky chemical adducts. Features of premature aging often occur in individuals with mutational defects in genes specifying protein components of the NER pathway, including those with TTD[16] (see DNA damage theory of aging).