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Trichothiodystrophy 2, photosensitive(TTD2)

MedGen UID:
905904
Concept ID:
C4225344
Disease or Syndrome
Synonym: TTD2
 
Gene (location): ERCC3 (2q14.3)
 
Monarch Initiative: MONDO:0014615
OMIM®: 616390

Definition

Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder. Patients with TTD have not been reported to have a predisposition to cancer (summary by Faghri et al., 2008). For a discussion of genetic heterogeneity of TTD, see 601675. [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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.   https://medlineplus.gov/genetics/condition/trichothiodystrophy

Clinical features

From HPO
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).
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.
Agenesis of maxillary lateral incisor
MedGen UID:
342374
Concept ID:
C1849950
Finding
Agenesis of one or more maxillary lateral incisor, comprising the maxillary lateral primary incisor and maxillary lateral secondary incisor.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
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.
Coarse hair
MedGen UID:
124454
Concept ID:
C0277959
Finding
Hair shafts are rough in texture.
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.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTrichothiodystrophy 2, photosensitive

Professional guidelines

PubMed

Alapetite C, Benoit A, Moustacchi E, Sarasin A
J Invest Dermatol 1997 Feb;108(2):154-9. doi: 10.1111/1523-1747.ep12332692. PMID: 9008227

Recent clinical studies

Etiology

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
Theil AF, Botta E, Raams A, Smith DEC, Mendes MI, Caligiuri G, Giachetti S, Bione S, Carriero R, Liberi G, Zardoni L, Swagemakers SMA, Salomons GS, Sarasin A, Lehmann A, van der Spek PJ, Ogi T, Hoeijmakers JHJ, Vermeulen W, Orioli D
Am J Hum Genet 2019 Aug 1;105(2):434-440. doi: 10.1016/j.ajhg.2019.06.017. PMID: 31374204Free PMC Article
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Stefanini M, Giliani S, Nardo T, Marinoni S, Nazzaro V, Rizzo R, Trevisan G
Mutat Res 1992 Mar;273(2):119-25. doi: 10.1016/0921-8777(92)90073-c. PMID: 1372095

Diagnosis

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
Jen M, Nallasamy S
Clin Dermatol 2016 Mar-Apr;34(2):242-75. Epub 2015 Dec 2 doi: 10.1016/j.clindermatol.2015.11.008. PMID: 26903188
Hosseini M, Ezzedine K, Taieb A, Rezvani HR
J Invest Dermatol 2015 Feb;135(2):341-351. Epub 2014 Oct 9 doi: 10.1038/jid.2014.365. PMID: 25296907
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
Stefanini M, Giliani S, Nardo T, Marinoni S, Nazzaro V, Rizzo R, Trevisan G
Mutat Res 1992 Mar;273(2):119-25. doi: 10.1016/0921-8777(92)90073-c. PMID: 1372095

Therapy

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
Hosseini M, Ezzedine K, Taieb A, Rezvani HR
J Invest Dermatol 2015 Feb;135(2):341-351. Epub 2014 Oct 9 doi: 10.1038/jid.2014.365. PMID: 25296907
Falik-Zaccai TC, Keren Z, Slor H
Pediatr Endocrinol Rev 2009 Dec;7(2):37-42. PMID: 20118892
Jaspers NG
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Takayama K, Salazar EP, Broughton BC, Lehmann AR, Sarasin A, Thompson LH, Weber CA
Am J Hum Genet 1996 Feb;58(2):263-70. PMID: 8571952Free PMC Article

Prognosis

Moriwaki S, Saruwatari H, Kanzaki T, Kanekura T, Minoshima S
J Dermatol 2014 Aug;41(8):705-8. Epub 2014 Jul 2 doi: 10.1111/1346-8138.12549. PMID: 24986372
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
Kleijer WJ, Laugel V, Berneburg M, Nardo T, Fawcett H, Gratchev A, Jaspers NG, Sarasin A, Stefanini M, Lehmann AR
DNA Repair (Amst) 2008 May 3;7(5):744-50. Epub 2008 Mar 10 doi: 10.1016/j.dnarep.2008.01.014. PMID: 18329345
Alapetite C, Benoit A, Moustacchi E, Sarasin A
J Invest Dermatol 1997 Feb;108(2):154-9. doi: 10.1111/1523-1747.ep12332692. PMID: 9008227
Arlett CF, Harcourt SA, Cole J, Green MH, Anstey AV
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Clinical prediction guides

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
Maguina M, Kang PB, Tsai AC, Pacak CA
Muscle Nerve 2023 Feb;67(2):101-110. Epub 2022 Oct 3 doi: 10.1002/mus.27721. PMID: 36190439Free PMC Article
Theil AF, Mandemaker IK, van den Akker E, Swagemakers SMA, Raams A, Wüst T, Marteijn JA, Giltay JC, Colombijn RM, Moog U, Kotzaeridou U, Ghazvini M, von Lindern M, Hoeijmakers JHJ, Jaspers NGJ, van der Spek PJ, Vermeulen W
Hum Mol Genet 2017 Dec 1;26(23):4689-4698. doi: 10.1093/hmg/ddx351. PMID: 28973399Free PMC Article
Suhasini AN, Brosh RM Jr
Mutat Res 2013 Apr-Jun;752(2):138-152. Epub 2012 Dec 28 doi: 10.1016/j.mrrev.2012.12.004. PMID: 23276657Free PMC Article
Stefanini M, Giliani S, Nardo T, Marinoni S, Nazzaro V, Rizzo R, Trevisan G
Mutat Res 1992 Mar;273(2):119-25. doi: 10.1016/0921-8777(92)90073-c. PMID: 1372095

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