Trichothiodystrophy (TTD) is anautosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down intotricho – "hair",thio – "sulphur", anddystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of theectoderm andneuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy havephotosensitivity, which divides the classification into syndromes with or withoutphotosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.[2]
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.[3] 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,[4] is anautosomalrecessive[5] inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature.[6]: 501 There is a photosensitive syndrome, PBIDS.[7]
BIDS is associated with the geneMPLKIP (TTDN1).[8] IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is theTay syndrome or sulfur-deficient brittle hair syndrome, first described by Tay in 1971.[9] (Chong Hai Tay was the Singaporean doctor who was the first doctor in South East Asia to have a disease named after him.[10]) Tay syndrome should not be confused with theTay–Sachs disease.[6]: 485 [11][12][13] It is anautosomalrecessive[14]congenital disease.[6]: 501 [15] In some cases, it can be diagnosed prenatally.[16] IBIDS syndrome is nonphotosensitive.
All photosensitive TTD syndromes have defects in thenucleotide 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.[18] These types of defects can result in other rare autosomal recessive diseases likexeroderma pigmentosum andCockayne syndrome.[19]
Currently, mutations in four genes are recognized as causing the TTD phenotype, namelyTTDN1,ERCC3/XPB,ERCC2/XPD andTTDA.[20] Individuals with defects inXPB,XPD andTTDA are photosensitive, whereas those with a defect inTTDN1 are not. The three genes,XPB,XPD andTTDA, encode protein components of the multi-subunittranscription/repair factor IIH (TFIIH). This complex factor is an important decision maker inNER that opens theDNA 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[21] (seeDNA damage theory of aging).
The non-photosensitive forms are caused byAARS1,CARS1,TTDN1,RNF113A,TARS1 andMARS1 genes.[22] The function ofAARS1,CARS1 andTARS1 gene are to charge tRNAs with amino acid.[23] According to one study, theTTDN1 gene plays role in mitosis.[24] Some study suggests that theRNF113A gene is a part ofspliceosome and it can terminate CXCR4 pathway throughCXCR4 Ubiquitination.[25][26][27]
The diagnosis of TTD can by made by showing low sulfur content by biochemical assay of hair shafts, also, it can by following findings:[29]
Trichoschisis (broken or split hairs)
Alternating light and dark bands called 'tiger-tail pattern' are found in the hair shaft, which can be detected by polarised light microscopy or trichoscopy.
A severely damaged or absent hair cuticle can be seen by electron microscopy scanning.
This disease doesn't have a cure, although it can be managed symptomatically.[30] Patients with Photosensetive forms should be provided with sun protection.[30][31]
^Lambert WC, Gagna CE, Lambert MW (2010). "Trichothiodystrophy: Photosensitive, TTD-P, TTD, Tay Syndrome".Diseases of DNA Repair. Advances in Experimental Medicine and Biology. Vol. 685. pp. 106–10.doi:10.1007/978-1-4419-6448-9_10.ISBN978-1-4419-6447-2.PMID20687499.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Liang, Christine; Kraemer, Kenneth H.; Morris, Andrea; Schiffmann, Raphael; Price, Vera H.; Menefee, Emory; DiGiovanna, John J. (February 2005). "Characterization of tiger tail banding and hair shaft abnormalities in trichothiodystrophy".Journal of the American Academy of Dermatology.52 (2):224–232.doi:10.1016/j.jaad.2004.09.013.PMID15692466.
^abcFreedberg, et al. (2003).Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill.ISBN0-07-138076-0.
^Hashimo S, and Egly JM. Trichothiodystrophy view from the molecular basis of DNA repair transcription factor TF11H.www.oxfordjournals.org/content/18/R2/R224
^Tay CH (1971). "Ichthyosiform erythroderma, hair shaft abnormalities, and mental and growth retardation. A new recessive disorder".Arch Dermatol.104 (1):4–13.doi:10.1001/archderm.104.1.4.PMID5120162.
^Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).Dermatology: 2-Volume Set. St. Louis: Mosby.ISBN978-1-4160-2999-1.
^Hashimoto S, and Egly JM, www.oxfordjournals.org/content/18/R2/R224
^Stefanini M, B. E.; Botta, E.; Lanzafame, M.; Orioli, D. (January 2010). "Trichothiodystrophy: from basic mechanisms to clinical implications".DNA Repair.9 (1):2–10.doi:10.1016/j.dnarep.2009.10.005.PMID19931493.
^Kleijer WJ, van der Sterre ML, Garritsen VH, Raams A, Jaspers NG (Dec 2007). "Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk".Prenat. Diagn.27 (12):1133–1137.doi:10.1002/pd.1849.PMID17880036.S2CID23534246.
^Peserico, A.; Battistella, P. A.; Bertoli, P. (1 January 1992). "MRI of a very rare hereditary ectodermal dysplasia: PIBI(D)S".Neuroradiology.34 (4):316–317.doi:10.1007/BF00588190.PMID1528442.S2CID31063628.
