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Trichothiodystrophy (TTD) is an
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
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 The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...
and
neuroectoderm Neuroectoderm (or neural ectoderm or neural tube epithelium) consists of cells derived from ectoderm. Formation of the neuroectoderm is first step in the development of the nervous system. The neuroectoderm receives bone morphogenetic protein-inhi ...
. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have
photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...
, which divides the classification into syndromes with or without
photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...
; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.


Presentation

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. 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 An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . There is a photosensitive syndrome, PBIDS. BIDS is associated with the gene
MPLKIP M-phase-specific PLK1-interacting protein (TTD non-photosensitive 1 protein) is a protein that in humans is encoded by the MPLKIP gene (previously known as C7orf11). Patients with an inherited defect in both alleles of the gene suffer from trichot ...
(TTDN1). IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is the
Tay 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 lit ...
or sulfur-deficient brittle hair syndrome, first described by Tay in 1971. (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 Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby ...
. It is an
autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...
recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
disease. In some cases, it can be diagnosed prenatally. IBIDS syndrome is nonphotosensitive.


Cause

The photosensitive form is referred to as PIBIDS, and is associated with
ERCC2 __NOTOC__ ERCC2, or XPD is a protein involved in transcription-coupled nucleotide excision repair. The XPD (ERCC2) gene encodes for a 2.3-kb mRNA containing 22 exons and 21 introns. The XPD protein contains 760 amino acids and is a polypeptide wi ...
and
ERCC3 XPB (xeroderma pigmentosum type B) is an ATP-dependent DNA helicase in humans that is a part of the TFIIH transcription factor complex. Structure The 3D-structure of the archaeal homolog of XPB has been solved by X-ray crystallography by Dr. J ...
.


Photosensitive forms

All photosensitive TTD syndromes have defects in the
nucleotide excision repair Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleo ...
(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. These type of defects can result in other rare autosomal recessive diseases like
xeroderma pigmentosum Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun ...
and
Cockayne syndrome Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight ( photo ...
.


DNA repair

Currently, mutations in four genes are recognized as causing the TTD phenotype, namely ''TTDN1'', '' XPB'', ''
XPD ''XPD'' is a spy novel by Len Deighton, published in 1981, and set in 1979, roughly contemporaneous with the time it was written. It concerns a plan by a group of former SS officers to seize power in West Germany, in which they intend to publi ...
'' and '' TTDA''. 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 (see
DNA damage theory of aging The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DN ...
).


Diagnosis


Treatment


See also

*
Skin lesion A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
*
List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...


References


External links


NIH document on Tay syndrome
{{Progeroid syndromes Genodermatoses Autosomal recessive disorders Congenital disorders Rare diseases Syndromes DNA replication and repair-deficiency disorders Progeroid syndromes