Uncombable hair syndrome

From WikiMD's Wellnesspedia

Uncombable hair syndrome is a rare structural anomaly of the hair with a variable degree of effect. It was first reported in the early 20th century.[1] It typically becomes apparent between the ages of 3 months and 12 years.[2]

Presentation[edit | edit source]

The shaft of normal hair (left) and hair in uncombable hair syndrome (right).

The hair is normal in quantity and is usually silvery-blond or straw-colored. It is disorderly, it stands out from the scalp, and cannot be combed flat. It can be controlled by braiding methods. The underlying structural anomaly is longitudinal grooving of the hair shaft, which appears triangular in cross section. This is caused by mutations in one of three possible genes, PADI3, TGM, or TCHH3. The characteristic hair shaft anomaly can be demonstrated in asymptomatic family members by scanning electron microscopy. To be noticeable, 50% of hairs must be affected by the structural abnormality. Improvement often occurs in later childhood.[3][4] An autosomal dominant mode of inheritance has been suggested though an autosomal recessive pattern with varying degrees of penetrance has also been noted.[1][3] The stiffness of the uncombable hair has been reasoned to be due to the triangular form of the hair shaft in cross section. It has been suggested that the condition may result from premature keratinization of the inner root sheath.[3]

Uncombable Hair Syndrome 1[edit | edit source]

Uncombable Hair Syndrome 1 is caused by a defect in the trichohyalin gene(TCHH) and found in hair follicles where hair grows and in some parts of hair strands.[5] The trichohyalin gene is produced and changed by alternative proteins, so it will attach to alternative trichoyalin proteins and to molecules referred to as albuminoid intermediate filaments to form organized cross-links. These linked-type dense networks provides the hair shaft its cylindrical form.[5] The TCHH mutation that has been known, results in a stop signal within the directions accustomed build trichohyalin, which leads to a short supermolecule with reduced activity. Due to the reduced activity the cross-sectional portion of the shaft becomes flat.[5] This in turn, leads to frizzly hair which will not lie flat, resulting in uncombed hair.[5] The chromosomal location for this TCHH gene is located on chromosome 1.[5] It is still being decided whether TCHH is autosomal dominant, or autosomal recessive.[6] In an experiment, they identified the causative mutations of UHS in 3 genes; PADI3, TGM3, and TCHH in 11 children. These children carried homozygous/heterozygous mutations in those 3 genes, which resulted in autosomal recessive inheritance. Because it was identified as autosomal recessive inheritance, scanning electron microscopy was performed in order to rule out autosomal dominance since this type of gene can also be autosomal dominant to a certain extent.[6]

Uncombable Hair Syndrome 2[edit | edit source]

Uncombable Hair Syndrome 2 is caused by a defect in the Transglutaminase 3 gene. This gene helps provide directions for creating a catalyst known as Transglutaminase 3. This gene is found in bound skin cells known as keratinocytes and corneocytes, furthermore as in varied structures that frame scalp hair, the root, and the strand of the hair.[7] It helps the macromolecules bind to every alternative protein.[7] It helps put the cross-links between the proteins to be at equilibrium. Therefore, the cross-links helps provide strength and structure cells to the skin and hair cells.[7] The chromosomal location of Transglutaminase 3 is located on chromosome 20.[7] An experiment was done where Transglutaminase 3 reduced in esophageal cancer.[8] They used western blot analysis and by the polymerase-chain reaction.[9] With the 58 pairs of tissues that were sampled, it was confirmed that Transglutaminase 3 is closely related to growth proliferation and migration. However, the overexpression of this gene induces cell proliferation, migration, invasion, and promotes programmed cell death. This came to show that Transglutaminse 3 will be a candidate growth and could function as a helpful biomarker and therapeutic target to esophageal cancer treatment.[8]

Uncombable Hair Syndrome 3[edit | edit source]

Uncombable Hair Syndrome 3 is caused by a defect in the peptidylarginine deiminase 3 gene(PADI3) and located on chromosome 1. The PADI3 gene provides instructions for creating an enzyme called peptidylargine deiminase 3. PADI3 is found within the skin's extreme external surface, inside cells called karinocytes.[10] The protein also contributes to hair follicles that are specialized structures within the skin where the development happens. In these hair follicles, the PADI3 gene adjusts proteins that are included in giving structure to the hair strand.[10] The PADI3 gene also involves a process called deimination. This process modifies the protein's intuitive with other proteins[10] An experiment was performed in where the PADI3 is found in central centrifugal cicatricial alopecia which is mostly found in African women that suggests an autosomal dominant trait to occur. With this experiment, they performed a process called immunoblotting and immunofluorescence. With immunoblotting it appeared that the transfected cells had a marginally lower expression of the mutant compared to the wildtype.[11] With immunofluorescence it resulted in an irregular intracellular location of the protein.[12] Therefore, with these two analysis, it helped conclude that there was a reduction in enzymatic action that encodes a protein to hair shaft arrangement, which relates to central centrifugal cicatricial alopecia(CCCA).[11]

Diagnosis[edit | edit source]

Differential diagnosis[edit | edit source]

Other syndromes with hair abnormalities may also show features of uncombable hair syndrome such as Rapp–Hodgkin ectodermal dysplasia syndrome, loose anagen syndrome, EEC syndrome (ectodermal dysplasia, ectrodactyly and cleft lip/palate) and familial tricho-odonto-onychial ectodermal dysplasia with syndactyly. However, unlike these conditions, uncombable hair syndrome alone is not associated with physical, neurologic, or mental abnormalities.[1]

According to the U.S. National Institute of Health, the condition tends to develop in childhood (age 3-12) and resolve by adolescence.[2]

History[edit | edit source]

A possible case of uncombable hair syndrome was reported in 1912 by A.F. Le Double and F. Houssay.[13] The syndrome was described in 1973 by A. Dupré, P. Rochiccioli and J.L. Bonafé, who named it "cheveux incoiffables".[13] Later that year it was independently described as "spun-glass hair" by J.D. Stroud and A.H. Mehregan.[13] The famous term was coined in the early eighties.

See also[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2
  2. 2.0 2.1 "Girl With Uncombable Hair Syndrome Rocks Her Rare Condition With Style". Parents. Retrieved 2019-11-12.
  3. 3.0 3.1 3.2 "Uncombable hair syndrome". Orphanet. Retrieved 1 September 2012.
  4. Trüeb, Ralph (September 2003). "Uncombable hair syndrome" (PDF). Orphanet Encyclopedia. Retrieved 1 September 2012.
  5. 5.0 5.1 5.2 5.3 5.4 Reference, Genetics Home. "TCHH gene". Genetics Home Reference. Retrieved 2020-04-29.
  6. 6.0 6.1
  7. 7.0 7.1 7.2 7.3 Reference, Genetics Home. "TGM3 gene". Genetics Home Reference. Retrieved 2020-04-29.
  8. 8.0 8.1
  9. "OMIM Entry - * 600238 - TRANSGLUTAMINASE 3; TGM3". omim.org. Retrieved 2020-04-29.
  10. 10.0 10.1 10.2 Reference, Genetics Home. "PADI3 gene". Genetics Home Reference. Retrieved 2020-04-29.
  11. 11.0 11.1 "OMIM Entry - * 606755 - PEPTIDYLARGININE DEIMINASE, TYPE III; PADI3". omim.org. Retrieved 2020-04-29.
  12. 13.0 13.1 13.2

External links[edit | edit source]

Classification
External resources


Wiki.png

Navigation: Wellness - Encyclopedia - Health topics - Disease Index‏‎ - Drugs - World Directory - Gray's Anatomy - Keto diet - Recipes

Search WikiMD


Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro) available.
Advertise on WikiMD

WikiMD is not a substitute for professional medical advice. See full disclaimer.

Credits:Most images are courtesy of Wikimedia commons, and templates Wikipedia, licensed under CC BY SA or similar.


Contributors: Prab R. Tumpati, MD