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uncombable hair syndrome

Uncombable hair syndrome

Uncombable hair syndrome also known as unmanageable hair syndrome, “spun glass hair syndrome,” “pili trianguli et canaliculi,” or “cheveux incoiffables” is a rare anomaly of the hair shaft that occurs in children and improves with age 1. Patients with uncombable hair syndrome have unruly, dry, frizzy hair (spun-glass hair) that cannot be combed flat 2. Uncombable hair syndrome develops in childhood, often between infancy and age 3, but can appear as late as age 12 3. Affected children have light-colored hair, described as blond or silvery with a glistening sheen. The hair does not grow downward but out from the scalp in multiple directions. Despite its appearance, the hair is not fragile or brittle, and it grows at a normal or slightly slower rate. Only scalp hair is affected in uncombable hair syndrome.

For unknown reasons, uncombable hair syndrome usually improves over time. By adolescence individuals with uncombable hair syndrome have hair that lies flat and has normal or nearly normal texture.

The prevalence of uncombable hair syndrome is unknown; at least 100 cases have been described in the scientific literature. There are likely more people who are undiagnosed because adults who seem unaffected may have had uncombable hair syndrome in childhood.

Most uncombable hair syndrome cases are isolated, but in some cases it has been described in association with other diseases, such as ectodermal dysplasias, Bork syndrome and Angel-shaped phalangoepiphyseal dysplasia. Uncombable hair syndrome has been found to be caused by mutations in the genes PADI3, TGM3, and TCHH. These three genes code for proteins that are involved in hair shaft formation 4. Uncombable hair syndrome appears to be inherited in an autosomal recessive fashion; however, cases inherited in an autosomal dominant manner may also exist, as there are other genes involved in hair formation 1. Uncombable hair syndrome often spontaneously regresses in late childhood 5. Some published studies suggest that biotin may improve the condition 6.

Uncombable hair syndrome causes

Uncombable hair syndrome is caused by mutations in the PADI3, TGM3, or TCHH gene. These genes provide instructions for making proteins that help give structure to the hair strand (shaft).

The proteins produced from the PADI3 and TGM3 genes modify the protein produced from the TCHH gene, known as trichohyalin. The modified trichohyalin can attach (bind) to other trichohyalin proteins and to molecules called keratin intermediate filaments to create organized cross-links. These links form dense networks that provide structure to the hair shaft and give it a cylindrical shape.

PADI3, TGM3, or TCHH gene mutations likely lead to the production of proteins with little or no activity. As a result, the shape of the hair shaft is altered. Instead of having a cylindrical shape, it has a triangular, heart-like, or flat cross-section. Sometimes all of these irregular shapes can occur along the length of a single strand of hair. Because of the angular shape of the hair shaft, the hair will not lie flat. In children with uncombable hair syndrome, 50 to 100 percent of their strands of hair have an irregular shape. Additionally, the abnormal hair reflects light differently than normal hair, accounting for its glistening sheen.

Some people with uncombable hair syndrome do not have an identified mutation in one of these three genes. The cause of the condition in these individuals is unknown.

Uncombable hair syndrome inheritance pattern

When uncombable hair syndrome is caused by mutations in the PADI3, TGM3, or TCHH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

In other cases, uncombable hair syndrome appears to be inherited in an autosomal dominant pattern with reduced penetrance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation. Reduced penetrance means that not all people with a mutation in the responsible gene will have the condition. For this reason, conditions with reduced penetrance may appear to “skip a generation” or may appear to occur for the first time (or only once) in a family. In these cases an affected person usually inherits the mutation from one affected parent, although the associated gene is unknown.

In still other cases of uncombable hair syndrome, the inheritance pattern is unknown.

People with specific questions about genetic risks or genetic testing for themselves or family members should speak with a genetics professional.

Resources for locating a genetics professional in your community are available online:

Uncombable hair syndrome symptoms

Uncombable hair syndrome is a rare disorder of the hair shaft of the scalp. Uncombable hair syndrome is usually characterized by silvery-blond or straw-colored hair that is disorderly; stands out from the scalp; and cannot be combed flat. Uncombable hair syndrome may first become apparent any time between the ages of 3 months and 12 years 5. Uncombable hair syndrome only affects the scalp hair. The quantity of hair remains normal, but the hair often grows slowly 7. Over time the hair becomes progressively silvery-blond or straw-colored; dry and disordered (standing out and growing in different directions); and unmanageable to comb flat 5. In some cases, constant efforts to groom the hair lead to breakage, but increased fragility is not a constant feature of the condition. In later childhood, there is usually a considerable amount of spontaneous improvement 8.

In cases where uncombable hair syndrome is part of a syndrome, there may be other signs and symptoms present; therefore, it is important to determine whether the uncombable hair syndrome is isolated or syndromic.

Uncombable hair syndrome diagnosis

A diagnosis of uncombable hair syndrome is made by observing the characteristic symptoms of the condition, as well observing the hair shaft under a special microscope 5. When the individual hair strands are viewed under a microscope, the hair is either triangular or kidney-shaped on cross section, and has a canal-like longitudinal groove along one or two faces 9. People with concerns about symptoms of uncombable hair syndrome are encouraged to speak with their dermatologist about being evaluated for this condition. The recent discovery of the genes associated with the condition may lead to genetic testing in the future.

Uncombable hair syndrome treatment

There is no definitive treatment for uncombable hair syndrome, but the condition usually improves or resolves on its own with the onset of puberty. Gentle hair care is generally recommended using conditioners and soft brushes, along with avoiding harsh hair treatments such as permanent waves (perms); chemical relaxants; or excessive brushing and blow drying. These strategies may improve the general manageability of the hair, although how well they work is subjective 8.

Another strategy that has been suggested to improve the appearance of the hair is the use of biotin supplements. One case report suggested significant improvement in hair strength and combability, with an increase in rate of growth after 4 months of supplementation 8.

Uncombable hair syndrome prognosis

Uncombable hair syndrome usually resolves on its own (spontaneously) by adolescence 8. Treatment is usually not necessary 10. In the cases, where uncombable hair syndrome is part of syndrome, the prognosis will depend on the specific syndrome and the signs and symptoms present in the person.

References
  1. Ü Basmanav FB, Cau L, Tafazzoli A, et al. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. Am J Hum Genet. 2016;99(6):1292–1304. doi:10.1016/j.ajhg.2016.10.004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142115
  2. Hicks J., Metry D.W., Barrish J., Levy M. Uncombable hair (cheveux incoiffables, pili trianguli et canaliculi) syndrome: brief review and role of scanning electron microscopy in diagnosis. Ultrastruct Pathol. 2001;25:99–103.
  3. Uncombable hair syndrome. https://ghr.nlm.nih.gov/condition/uncombable-hair-syndrome
  4. Basmanav, FBÜ & cols. Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. The American Journal of Human Genetics. 2016; 99(6):1292-1304. http://www.cell.com/ajhg/abstract/S0002-9297(16)30440-2
  5. Uncombable hair syndrome. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1410
  6. Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to Biotin. Pediatr Dermatol. 2007 May-Jun;24(3):E14-6. https://doi.org/10.1111/j.1525-1470.2007.00385.x
  7. Rieubland C, de Viragh PA & Addor MC. Uncombable hair syndrome: a clinical report. Eur J Med Genet. 2007 Jul-Aug; http://www.ncbi.nlm.nih.gov/pubmed/17526443
  8. Calderon P, Otberg N, Shapiro J. Uncombable hair syndrome. J Am Acad Dermatol. September, 2009; 61(3):512-515. https://www.ncbi.nlm.nih.gov/pubmed/19700017
  9. Jarell AD, Hall MA, Sperling LC. Uncombable hair syndrome. Pediatr Dermatol. 2007 Jul-Aug; 24(4):436-438. https://www.ncbi.nlm.nih.gov/pubmed/17845183
  10. Ralph Trüeb. Uncombable hair syndrome. Orphanet Encyclopedia. September 2003. https://www.orpha.net/data/patho/GB/uk-uncombable.pdf
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