Trichothiodystrophy (syn. Tay syndrome) is a recessive hereditary disease (the faulty gene is carried by both parents) characterised by sulphur-deficient brittle hair.
It was first described by Dr. Tay Chong Hai in 1971.

The hair deformity may exist with or without other symptoms which may include:
• skin resembling fish scales (ichthyosiform erythroderma).
• light sensitivity (photosensitivity) in 75%+ of reported cases.
• abnormalities of finger-nails and toe-nails onchodystrophy.
• premature aging (progeria-like).
• low level weight gain.

The hair-shaft is brittle - it fractures and severs on emergence from its host follicle. The overall appearance being of short, sparse hair.
Eyebrows and eyelashes may be inculcated. There is currently no treatment for TrichoThioDystrophy.

Examination of the hair reveals that its cross sectional shape is oval. There are also irregularities in its diameter and pigmentation. Its cuticle may present with abnormalities or may be absent.

Where TTD is confirmed, hair samples tested will usually indicate a reduction of approximately 50% of normal levels of sulphur and cysteine.

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by Tolani Ojebuovboh

Trichothiodystrophy (TTD) also called Amish brittle hair syndrome is a rare autosomal recessive inherited disorder that affects many parts of the body. The Greek compound word trichothiodystrophy is derived from 3 other words: ‘tricho’ (hair), ‘thio’ (sulphur) and ‘dystrophy’ (wasting away). It is characterised by brittle, sparse and easily broken hairs, caused by a deficiency in sulphur, required for the strength of hair. Sulphur is an essential component of proteins and biologic compounds. Mild cases may involve only the hair while more severe cases involve damage to the structure of hair, intellectual disability, recurrent infections, delayed development and some patients might even die at early childhood.


It is such an extremely rare disease with only an estimated incidence of about 1 in 1 million newborns in the US and Europe. Only about 100 affected individuals have been reported worldwide.



In 1971, Tay described the distinct characteristics of TTD. The term trichothiodystrophy was introduced by Price et al in 1980, he noted some symptoms of the condition such as sulphur deficient brittle hair.



Signs that a woman might be pregnant with a child that has TTD include:

o         preeclampsia, high blood pressure and excess protein in the urine after 20 weeks of pregnancy

o         HELLP syndrome, a life threatening liver disorder thought to be a type of severe preeclampsia

o         premature birth


The symptoms of TTD include:

o         low birth weight and poor weight gain

o         slow growth

o         short stature compared with other kids in the same age range

o        delayed development

o   brain abnormalities

o   intellectual disabilities

o   ichthyosis (a congenital skin condition that causes the epidermis to become dry and rough like fish scales)

o   congenital cataracts clouding the lens in both eyes from birth, leading to a decrease in vision

o   recurrent infections especially those of the respiratory system

o   poor coordination

o   abnormalities of the toe and finger nails

o   skeletal abnormalities

o   premature aging of facial features, osteoporosis (a disease that thins and weakens the bones to the point that they become fragile and break easily) and hearing loss

o   abnormal brittle, fragile and sparse hairs

o   dental abnormalities

o   sensitivity to ultraviolet rays from the sun in patients with the photosensitive type


TTD can be sub classified into 4 syndromes: BIDS, PBIDS, IBIDS and PIBIDS.

      i.               BIDS Syndrome

BIDS syndrome is an acronym for brittle hair-ichthyosis-decreased fertility-short stature syndrome. It is also called Amish brittle hair syndrome and hair brain syndrome. It is an autosomal recessive inherited disease characterised by brittle hair, ichthyosis, decreased fertility and short stature. Patients with BIDS syndrome are not photosensitive.


     ii.              PBIDS Syndrome

PBIDS syndrome is an acronym for photosensitivity-brittle hair-ichthyosis-decreased fertility-short stature syndrome. The letters of the acronym PBIDS represent its characteristics. It is basically a photosensitive form of BIDS syndrome.


   iii.           IBIDS Syndrome

IBIDS syndrome is an acronym for intellectual impairment-brittle hair-ichthyosis-decreased fertility-short stature syndrome. It is also called Tay syndrome because it was first described by D-Tay in 1971 and sulphur-deficient brittle hair syndrome. It is an autosomal recessive congenital disease, characterised by intellectual impairment, brittle hair, ichthyosis, decreased fertility, short stature and non photosensitivity.

   iv.               PIBIDS syndrome is the photosensitive form of IBIDS syndrome.


TTD is inherited in an autosomal recessive pattern, both copies of the gene in each cell have mutations and both parents carry one copy of the mutated gene but do not show any signs or symptoms of the condition. The parents are just carriers of the abnormal gene in which they pass on to their children. In some forms of TTD the genetic cause is unknown. The XPB or ERCC3, XPD or ERCC2, GTF2H5 and MPLKIP or TTDN1 genes have been identified for their role in the development of TTD.

DNA or deoxyribonucleic acid is a complex molecule that encodes the genetic instructions used in the development and functioning of an organism, it contains all the information necessary to build and maintain an organism. DNA can be modified or damaged from endogenous sources such as reactive oxidative species (chemically reactive molecules containing oxygen) and exogenous sources such as ultraviolet (UV) ionizing radiation (UV light with radiation composed of particles that carry enough kinetic energy to liberate an electron from an atom or molecule, converting it to an ion) which will increase reactive oxidative specie levels dramatically damaging cell structures. This causes defects in successive DNA replication and errors in genetic information within the DNA. If damaged DNA is not repaired it can lead to a range of disorders with neurological abnormalities (abnormalities relating to the nervous system), developmental defects, photosensitivity, accelerated age process and cancer. NER (nucleotide excision repair) is the most important DNA repair system or pathway in the cells that detects and removes specific types of DNA lesions especially those induced by drugs used to fight against tumours and UV radiation, to maintain the integrity of the genetic information contained within the DNA. Defects in NER have been associated with some rare autosomal recessive diseases like TTD, Cockayn syndrome (CS) and xerodermal pigmentosum (XP). Cockayn syndrome is a genetic disease that results from an inability to repair damage to DNA. Xerodermal pigmentosum is an inherited condition characterized by an extreme sensitivity to ultraviolet rays from the sun.


The products of 11 genes participate in NER and their mutations have been associated with TTD, XP and CS. Three genes (XPB, XPD and GTF2H5) out of the 11 are involved in the basal transcription repair factor TFIIH. The proteins produced from genes XPB, XPD and GTF2H5 work together as part of a group of proteins called general transcription factor IIH (TFIIH) complex. These genes encode subunits of the transcription factor IIH (TFIIH) complex which initiates the NER when DNA is damaged and plays an active role in gene transcription, the first step in protein production. Gene transcription is needed for normal development of a child and studies have shown this may be responsible for other forms of TTD.


PIBIDS and PBIDS syndrome have defects in the NER systems. Mutations in the subunits of DNA TFIIH disturb regulatory activity and or the ability to act as catalyst (a substance that causes a chemical reaction to happen more quickly) of the 2 XPB, XPD helicase (an enzyme that unwinds double strand DNA to single DNA strands) or ATpases (a class of enzymes that is used to speed up the chemical process of decomposing adenosine triphosphate, a substance that provides energy for many metabolic processes, to form adenosine diphosphate, a lower energy form of adenosine triphosphate). This results in a defective DNA repair and transcription system and disturbs the architecture of the TFIIH complex and its ability to transactivate certain nuclear receptor responsive genes. The photosensitive form of TTD, results from mutations in any of XPB, XPD and GTF2H5 genes which reduces the amount of the complex in cells therefore impairing DNA repair and gene transcription. An inability of the body to repair DNA causes patients with TTD to get sunburns easily when exposed to UV light.


The NER defect is not present in non photosensitive TTD. In less than 20% of cases of non-photosensitive TTD, mutations in MPLKIP gene have been reported to be the cause. Unfortunately, very little is known of the MPLKIP gene, the protein it produces, its function or how its mutations cause the various characteristics of TTD.


Clinical Features

Babies with TTD are born with shiny transparent skin known as collodion baby. The clinical features of TTD are photosensitivity, ichthyosis, brittle hair, decreased fertility, intellectual impairment and short stature.

a.       Photosensitivity

The defects in NER pathway which results in inefficient removal of DNA lesions caused by UV damage make a majority of TTD patients photosensitive. Patients show strong sensitivity to ultraviolet A and B light. Patients must not stay in the sun or stand the risk of sunburn. Despite the link between photosensitivity and reduced capacity of DNA repairs, no association with cancer and pigmentory abnormalities have been identified. Patients do not develop other sun related problems like freckling of the skin, skin cancer or even sweat. It has been reported that the severity of photosensitivity declines with age.


b.       Ichthyosis

Ichthyosis characterised by dry crackled skin covered with thin adherent scales (Fig. 2) is often experienced by patients with TTD.


It has been reported in many cases of TTD, that follicular keratosis (a cutaneous condition characterized by a horny growth) may be a sign of ichthyosis (PFOND, 2012). 

c.     Brittle hair

Patients have abnormally brittle, sparse, dry and fragile hair (Fig. 2) caused by the decrease in the production of sulphur matrix proteins (a member of the family of keratins) reducing effective cyteine (a sulphur containing amino acids) content. A microscope might reveal a pattern of alternating light and dark bands on the hair shaft, trichoschisis and the absence of or a defective cuticle.


d.       Decreased fertility

    Spermatogenesis, the process of male gamete (a mature sexual reproductive cell as a sperm or egg) formation requires the production of sulphur containing proteins. Gonadial (a sex gland in which gametes are produced, an ovary and testis) defects and decreased fertility due to sulphur deficiency is a common feature. Absent breast tissue, oligomenorrhea (infrequent or very light menstruation) and delayed menarche (first menstrual period) have been reported in female patients with under developed genitalia. In male patients with PIBIDS, testicular failure has been reported.


e.       Intellectual impairment

Mental retardation with low IQ, delayed physical maturation, defects in the development of the nervous system, lethargy (a lowered level of consciousness, with drowsiness, listlessness and apathy), irritability and unusual social behaviours, have been reported in patients with TTD. In severe cases, patients may have very poor mental and motor performance. However, despite these intellectual impairments, they are social, friendly, outgoing and engaging.


f.        Short stature

In patients with TTD, growth retardation and abnormal body proportions in the form of dwarfism, microcephalia (an abnormal smallness of the head), delayed puberty and skeletal malformations such as an unusual bird like facial appearance, are common features.


TTD can be diagnosed by physical examination of the hair, light microscopy and amino acid analysis.

Physical examination of a patient’s hair shows brittle, fragile, sparse and short hairs, the end product of hairs becoming exposed to the environment. Most patients also have sparse eyebrows and eyelashes (Fig. 1).

Light microscopy test of hair shafts reveal trichoschisis (broken or split hairs), and irregular and flattened hair shafts like trichorrhexis nodosa. Polarizing microscopy shows alternating light and dark bands, a tiger tail pattern.

An amino acid analysis is a tool for determining protein quantities and getting information on relative amino acid composition and free amino acids. An amino acid analysis that quantifies sulphur inversely correlates with the percentage of hairs showing abnormalities. It is the most dependable diagnostic test for TTD. It will show a decreased high sulphur matrix protein. High sulphur matrix protein is a member of the family of keratins, it is one of the rigid matrix proteins in which microfibrils of hair (a keratin protein) are embedded.  Reduced hair robustness is caused by the increased proportion of unstable disulfide conformers. Disulfide bonds are single covalent bonds (a bond formed by the sharing of one or more electrons especially pairs of electrons between atoms) between the sulphur atoms to two amino acids called cysteine. These disulfide bonds make up the cortex of the hair and its shape determines hair texture. Patients with xerodermal pigmentosum (XP) and Cockayn syndrome (CS) do not have sulphur deficient brittle hair phenotypes (a set of observable characteristics of an individual resulting from the interaction of its genotype with the environment).


Unfortunately, there is no cure for TTD. Prevention from sun induced skin damage especially for patients with photosensitive TTD is important. Dietary cytosine supplementation is sometimes recommended. Cytosine is a single-ringed, crystalline organic base that codes genetic information in the polynucleotide chain of DNA or RNA. Ribonucleic acid of RNA is used to translate instructions from DNA to make proteins in the body.



1.     Blume-Peytavi, U., Tosti, A., Whiting, D.A & Trub R.M. (2008). Hair growth and disorders, Germany: Graphics LLC.

2    Journal of Medical Genetics (2014). Trichothiodystrophy, photosensitive. Retrieved from:

3.       Trichothiodystrophy (May 2010). Retrieved from:    

      Trichothiodystrophy (Oct. 2014). Retrieve from:

5.      Trichothiodystrophy syndrome (Aug. 2012). Retrieved from:

      Trichothiodystrophy Syndromes (n.d). Retrieved from:


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