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Trichothiodystrophy 1, photosensitive(TTD1)

MedGen UID:
355730
Concept ID:
C1866504
Disease or Syndrome
Synonyms: PIBIDS syndrome; TAY SYNDROME; TRICHOTHIODYSTROPHY WITH CONGENITAL ICHTHYOSIS; TTD1
 
Gene (location): ERCC2 (19q13.32)
 
Monarch Initiative: MONDO:0011125
OMIM®: 601675
Orphanet: ORPHA670

Definition

Trichothiodystrophy is also associated with recurrent infections, particularly respiratory infections, which can be life-threatening. People with trichothiodystrophy may have abnormal red blood cells, including red blood cells that are smaller than normal. They may also have elevated levels of a type of hemoglobin called A2, which is a protein found in red blood cells. Other features of trichothiodystrophy can include dry, scaly skin (ichthyosis); abnormalities of the fingernails and toenails; clouding of the lens in both eyes from birth (congenital cataracts); poor coordination; and skeletal abnormalities including degeneration of both hips at an early age.

About half of all people with trichothiodystrophy have a photosensitive form of the disorder, which causes them to be extremely sensitive to ultraviolet (UV) rays from sunlight. They develop a severe sunburn after spending just a few minutes in the sun. However, for reasons that are unclear, they do not develop other sun-related problems such as excessive freckling of the skin or an increased risk of skin cancer. Many people with trichothiodystrophy report that they do not sweat.

Intellectual disability and delayed development are common in people with trichothiodystrophy, although most affected individuals are highly social with an outgoing and engaging personality. Some people with trichothiodystrophy have brain abnormalities that can be seen with imaging tests. A common neurological feature of this disorder is impaired myelin production (dysmyelination). Myelin is a fatty substance that insulates nerve cells and promotes the rapid transmission of nerve impulses.

Mothers of children with trichothiodystrophy may experience problems during pregnancy including pregnancy-induced high blood pressure (preeclampsia) and a related condition called HELLP syndrome that can damage the liver. Babies with trichothiodystrophy are at increased risk of premature birth, low birth weight, and slow growth. Most children with trichothiodystrophy have short stature compared to others their age. 

The signs and symptoms of trichothiodystrophy vary widely. Mild cases may involve only the hair. More severe cases also cause delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.

In people with trichothiodystrophy, tests show that the hair is lacking sulfur-containing proteins that normally gives hair its strength. A cross section of a cut hair shows alternating light and dark banding that has been described as a "tiger tail."

Trichothiodystrophy, commonly called TTD, is a rare inherited condition that affects many parts of the body. The hallmark of this condition is hair that is sparse and easily broken.  [from MedlinePlus Genetics]

Clinical features

From HPO
Squamous cell carcinoma
MedGen UID:
2874
Concept ID:
C0007137
Neoplastic Process
The presence of squamous cell carcinoma of the skin.
Skin basal cell carcinoma
MedGen UID:
1648304
Concept ID:
C4721806
Neoplastic Process
The presence of a basal cell carcinoma of the skin.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Intestinal obstruction
MedGen UID:
43933
Concept ID:
C0021843
Disease or Syndrome
Blockage or impairment of the normal flow of the contents of the intestine towards the anal canal.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Malabsorption
MedGen UID:
811453
Concept ID:
C3714745
Finding
Impaired ability to absorb one or more nutrients from the intestine.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Absence of subcutaneous fat
MedGen UID:
69138
Concept ID:
C0241267
Finding
Lack of subcutaneous adipose tissue.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.
Keratoconjunctivitis sicca
MedGen UID:
9620
Concept ID:
C0022575
Disease or Syndrome
Dryness of the eye related to deficiency of the tear film components (aqueous, mucin, or lipid), lid surface abnormalities, or epithelial abnormalities. Keratoconjunctivitis sicca often results in a scratchy or sandy sensation (foreign body sensation) in the eyes, and may also be associated with itching, inability to produce tears, photosensitivity, redness, pain, and difficulty in moving the eyelids.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Triangular mouth
MedGen UID:
336578
Concept ID:
C1849341
Finding
The presence of a triangular form of the mouth.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Freckling
MedGen UID:
5272
Concept ID:
C0016689
Finding
The presence of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Finding
Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.
Congenital nonbullous ichthyosiform erythroderma
MedGen UID:
38180
Concept ID:
C0079154
Disease or Syndrome
The term collodion baby applies to newborns who appear to have an extra layer of skin (known as a collodion membrane) that has a collodion-like quality. It is a descriptive term, not a specific diagnosis or disorder (as such, it is a syndrome). Affected babies are born in a collodion membrane, a shiny waxy outer layer to the skin. This is shed 10-14 days after birth, revealing the main symptom of the disease, extensive scaling of the skin caused by hyperkeratosis. With increasing age, the scaling tends to be concentrated around joints in areas such as the groin, the armpits, the inside of the elbow and the neck. The scales often tile the skin and may resemble fish scales.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Trichorrhexis nodosa
MedGen UID:
82668
Concept ID:
C0263485
Disease or Syndrome
Trichorrhexis nodosa is the formation of nodes along the hair shaft through which breakage readily occurs. It is thus a focal defect in the hair fiber that is characterized by thickening or weak points (nodes) that cause the hair to break off easily. The result is defective, abnormally fragile hair.
Brittle hair
MedGen UID:
120480
Concept ID:
C0263490
Disease or Syndrome
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Pili torti
MedGen UID:
82670
Concept ID:
C0263491
Finding
Pili (from Latin pilus, hair) torti (from Latin tortus, twisted) refers to short and brittle hairs that appear flattened and twisted when viewed through a microscope.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Fine hair
MedGen UID:
98401
Concept ID:
C0423867
Finding
Hair that is fine or thin to the touch.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Trichoschisis
MedGen UID:
698036
Concept ID:
C1274711
Disease or Syndrome
Transverse fractures through the hair shafts (trichoschisis). Trichoschisis is characterized by a sharp transverse fracture of the hair shaft.
Fragile nails
MedGen UID:
341661
Concept ID:
C1856963
Finding
Nails that easily break.
Tiger tail banding
MedGen UID:
892884
Concept ID:
C4073178
Finding
An abnormal appearance of hair under polarizing microscopy (using crossed polarizers), whereby hair shafts show striking alternating bright and dark bands, often referred to as tiger tail banding.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Microcornea
MedGen UID:
78610
Concept ID:
C0266544
Congenital Abnormality
A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTrichothiodystrophy 1, photosensitive

Professional guidelines

PubMed

Scott EM, Chandra S, Li J, Robinette ED, Brown MF, Wenger OK
J Clin Immunol 2020 Feb;40(2):321-328. Epub 2020 Jan 6 doi: 10.1007/s10875-019-00739-9. PMID: 31903518
Phillips TG, Slomiany WP, Allison R
Am Fam Physician 2017 Sep 15;96(6):371-378. PMID: 28925637
Rasheed M, Shahzad S, Zaeem A, Afzal I, Gul A, Khalid S
Arch Dermatol Res 2017 Dec;309(10):773-785. Epub 2017 Sep 14 doi: 10.1007/s00403-017-1780-x. PMID: 28913623

Recent clinical studies

Etiology

Ferri D, Orioli D, Botta E
Clin Genet 2020 Jan;97(1):12-24. Epub 2019 Apr 22 doi: 10.1111/cge.13545. PMID: 30919937
Abdel-Naser MB, Zouboulis CC
Rev Endocr Metab Disord 2016 Sep;17(3):353-365. doi: 10.1007/s11154-016-9368-x. PMID: 27342409
Alves R, Grimalt R
Curr Probl Dermatol 2015;47:55-66. Epub 2015 Feb 20 doi: 10.1159/000369405. PMID: 26370644
Theil AF, Hoeijmakers JH, Vermeulen W
Exp Cell Res 2014 Nov 15;329(1):61-8. Epub 2014 Jul 10 doi: 10.1016/j.yexcr.2014.07.008. PMID: 25016283
Norgauer J, Idzko M, Panther E, Hellstern O, Herouy Y
Eur J Dermatol 2003 Jan-Feb;13(1):4-9. PMID: 12609773

Diagnosis

Garon L, Kokta V, Coulombe J
JAMA Dermatol 2023 Aug 1;159(8):877. doi: 10.1001/jamadermatol.2023.0913. PMID: 37342013
Ferri D, Orioli D, Botta E
Clin Genet 2020 Jan;97(1):12-24. Epub 2019 Apr 22 doi: 10.1111/cge.13545. PMID: 30919937
Phillips TG, Slomiany WP, Allison R
Am Fam Physician 2017 Sep 15;96(6):371-378. PMID: 28925637
Lindsey SF, Tosti A
Curr Probl Dermatol 2015;47:139-49. Epub 2015 Feb 20 doi: 10.1159/000369414. PMID: 26370652
Norgauer J, Idzko M, Panther E, Hellstern O, Herouy Y
Eur J Dermatol 2003 Jan-Feb;13(1):4-9. PMID: 12609773

Therapy

Yew YW, Giordano CN, Spivak G, Lim HW
J Am Acad Dermatol 2016 Nov;75(5):873-882. doi: 10.1016/j.jaad.2016.03.044. PMID: 27745642
Lindsey SF, Tosti A
Curr Probl Dermatol 2015;47:139-49. Epub 2015 Feb 20 doi: 10.1159/000369414. PMID: 26370652
Alves R, Grimalt R
Curr Probl Dermatol 2015;47:55-66. Epub 2015 Feb 20 doi: 10.1159/000369405. PMID: 26370644
Shah P, He YY
Photochem Photobiol 2015 Mar-Apr;91(2):254-64. Epub 2015 Jan 14 doi: 10.1111/php.12406. PMID: 25534312Free PMC Article
Kamenisch Y, Berneburg M
J Investig Dermatol Symp Proc 2009 Aug;14(1):8-14. doi: 10.1038/jidsymp.2009.6. PMID: 19675546

Prognosis

Scott EM, Chandra S, Li J, Robinette ED, Brown MF, Wenger OK
J Clin Immunol 2020 Feb;40(2):321-328. Epub 2020 Jan 6 doi: 10.1007/s10875-019-00739-9. PMID: 31903518
Mendelsohn BA, Beleford DT, Abu-El-Haija A, Alsaleh NS, Rahbeeni Z, Martin PM, Rego S, Huang A, Capodanno G, Shieh JT, Van Ziffle J, Risch N, Alkuraya FS, Slavotinek AM
Am J Med Genet A 2020 Mar;182(3):513-520. Epub 2019 Dec 27 doi: 10.1002/ajmg.a.61450. PMID: 31880405Free PMC Article
Leemans G, De Raeve L, Keymolen K
J Eur Acad Dermatol Venereol 2020 Apr;34(4):876-879. Epub 2020 Jan 6 doi: 10.1111/jdv.16134. PMID: 31803976
Brooks BP, Thompson AH, Clayton JA, Chan CC, Tamura D, Zein WM, Blain D, Hadsall C, Rowan J, Bowles KE, Khan SG, Ueda T, Boyle J, Oh KS, DiGiovanna JJ, Kraemer KH
Ophthalmology 2011 Dec;118(12):2335-42. Epub 2011 Sep 28 doi: 10.1016/j.ophtha.2011.05.036. PMID: 21959366Free PMC Article
Ellis NA
Curr Opin Genet Dev 1997 Jun;7(3):354-63. doi: 10.1016/s0959-437x(97)80149-9. PMID: 9229111

Clinical prediction guides

Theil AF, Pines A, Kalayci T, Heredia-Genestar JM, Raams A, Rietveld MH, Sridharan S, Tanis SE, Mulder KW, Büyükbabani N, Karaman B, Uyguner ZO, Kayserili H, Hoeijmakers JH, Lans H, Demmers JA, Pothof J, Altunoglu U, El Ghalbzouri A, Vermeulen W
EMBO Mol Med 2023 Nov 8;15(11):e17973. Epub 2023 Oct 6 doi: 10.15252/emmm.202317973. PMID: 37800682Free PMC Article
Pascolini G, Gaudioso F, Baldi M, Alario D, Dituri F, Novelli A, Baban A
J Hum Genet 2023 Jun;68(6):437-443. Epub 2023 Feb 22 doi: 10.1038/s10038-023-01134-4. PMID: 36810639
Zurita M, Murillo-Maldonado JM
Int J Mol Sci 2020 Jan 17;21(2) doi: 10.3390/ijms21020630. PMID: 31963603Free PMC Article
Rudnicka L, Olszewska M, Waśkiel A, Rakowska A
Dermatol Clin 2018 Oct;36(4):421-430. Epub 2018 Aug 16 doi: 10.1016/j.det.2018.05.009. PMID: 30201151
Alves R, Grimalt R
Curr Probl Dermatol 2015;47:55-66. Epub 2015 Feb 20 doi: 10.1159/000369405. PMID: 26370644

Recent systematic reviews

Faghri S, Tamura D, Kraemer KH, Digiovanna JJ
J Med Genet 2008 Oct;45(10):609-21. Epub 2008 Jun 25 doi: 10.1136/jmg.2008.058743. PMID: 18603627Free PMC Article

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