What is monilethrix

Monilethrix is a rare inherited disorder that affects hair growth and is characterized by sparse, dry, and/or brittle hair that often breaks before reaching more than a few inches in length. Monilethrix most characteristic feature is that individual strands of hair have a beaded appearance like the beads of a necklace. The name monilethrix comes from the Latin word for necklace (monile) and the Greek word for hair (thrix). Noticeable when viewed under a microscope, the beaded appearance is due to periodic narrowing of the hair shaft. Another common symptom may be the appearance of elevated spots (papules) surrounding the hair follicles that may be covered with gray or brown crusts or scales (perifollicular hyperkeratosis). People with monilethrix also have sparse hair growth (hypotrichosis) and short, brittle hair that breaks easily.

Expression of monilethrix is variable; in mild cases, dystrophic hair may be confined to the occiput but more severely affected individuals have near total hair loss. In some cases, the hair loss persists throughout life; in others, regrowth of apparently normal hair may occur in adolescence or, temporarily, in pregnancy. Healy et al. ¹ reviewed the phenomenon of beading in this disorder. It had been shown that the periodicity is not diurnal and that it is not synchronous in independent follicles. In mild cases, close inspection is needed to confirm the presence of a few typical beaded hairs. Follicular keratosis and, in some families ², nail defects are associated. Electron microscopic studies of affected hair shafts showed defects in the microfibrillar structure of the cortex of the hair shaft and amorphous clumps of cysteine-rich material in both nodal and internodal regions. Hence, the genes for the structural proteins of the hair shaft were considered candidates for causative defects in monilethrix. The major structural proteins of hair are the relatively cysteine-rich ‘hard’ keratins, also found in nail.

Affected individuals usually have normal hair at birth, but the hair abnormalities develop within the first few months of life. In mild cases of monilethrix, only hair on the back of the head (occiput) or nape of the neck is affected, the hair may lack luster and there may be patchy areas of hair loss (alopecia). In more severe cases, hair over the whole scalp can be affected, as well as pubic hair, underarm hair, eyebrows, eyelashes, or hair on the arms and legs.

Occasionally, the skin and nails are involved in monilethrix. Some affected individuals have a skin condition called keratosis pilaris, which causes small bumps on the skin, especially on the scalp, neck, and arms. Affected individuals may also have abnormal fingernails or toenails.

In most cases, monilethrix is inherited as an autosomal dominant trait with variable penetrance.

Monilethrix affects males and females in equal numbers. The exact number of people affected by this disorder is not known ³. Monilethrix may be apparent at birth or by the age of two years. In some cases, the symptoms may improve at puberty or during pregnancy; in other cases, the symptoms may remain the same throughout life.

What parts of the body does monilethrix affect?

Monilethrix occurs mainly on the scalp, predominantly on the occiput and nape and occasionally on other scalp areas. Scalp involvement can be widespread or localized. Occasionally, the eyelashes, eyebrows, pubic, axillary, and limb hair are involved ⁴.

Figure 1. Monilethrix hair under microscope

Footnote: Optical microscopy of a monilethrix hair strand- hair looking like rosary beads, with nodes and constrictions

[Source ⁵ ]

Monilethrix causes

The cause of monilethrix remains unclear. To date, whether monilethrix is a disorder of the function or structure of the hair has not been determined. Some genetic studies suggest that monilethrix is likely caused by a mutation (change in a gene) in keratin (a type of protein found in the hair). At least four genes have been found to cause monilethrix. Mutations in the KRT81 gene, the KRT83 gene, the KRT86 gene, or the DSG4 gene account for most cases of monilethrix. These genes provide instructions for making proteins that give structure and strength to strands of hair.

Hair growth occurs in the hair follicle, a specialized structure in the skin. As the cells of the hair follicle mature to take on specialized functions (differentiate), they produce particular proteins and form the different compartments of the hair follicle and the hair shaft. As the cells in the hair follicle divide, the hair shaft is pushed upward and extends beyond the skin.

The KRT81, KRT83, and KRT86 genes provide instructions for making proteins known as keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of cells that make up the hair, skin, and nails. The KRT81 gene provides instructions for making the type II hair keratin K81 protein (K81); the KRT83 gene provides instruction for making the type II hair keratin K83 protein (K83); and the KRT86 gene provides instructions for making the type II hair keratin K86 protein (K86). The K81, K83, and K86 proteins are found in cells of the inner compartment of the hair shaft known as the cortex. These proteins give hair its strength and elasticity.

The DSG4 gene provides instructions for making a protein called desmoglein 4 (DSG4). This protein is found in specialized structures called desmosomes that are located in the membrane surrounding certain cells. These structures help attach cells to one another and play a role in communication between cells. The DSG4 protein is found in particular regions of the hair follicle, including the hair shaft cortex. Desmosomes in these regions provide strength to the hair and are thought to play a role in communicating the signals for cells to differentiate to form the hair shaft.

In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the KRT81, KRT83, KRT86, or DSG4 genes are related to the abnormality in the cortex or the beaded appearance of the hair.

Some people with monilethrix do not have a mutation in one of these genes. These individuals may have a genetic change in another gene, or the cause of the condition may be unknown.

Monilethrix inheritance pattern

Monilethrix can be inherited in an autosomal dominant or autosomal recessive manner ⁶. When monilethrix is caused by a mutation in one of the hair cortex keratin genes KRT81, KRT83, or KRT86, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

When monilethrix is caused by mutations in the DSG4 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. The clinical picture of autosomal recessive monilethrix is more severe than the dominant form, with more extensive alopecia of the scalp, body, and limbs, and a papular rash involving the extremities and periumbilical region ⁷.

In rare cases, monilethrix results from a new mutation in the gene and is not inherited.

Winter et al. ⁸ reported a 3-generation French family with autosomal dominant inheritance of monilethrix. The proband showed diffuse hypotrichosis and onychodystrophy from 2 months of age. Microscopic examination of the hair showed typically beaded or short dystrophic hair. She also had keratosis pilaris. At age 11 years, she still had hypotrichosis with partial regrowth. Her affected father had moderate hypotrichosis with less beaded hair. Most affected family members had hypotrichosis following shedding of initial hair, and then developed individually varying hair growth. Genetic analysis identified a heterozygous mutation in the KRT86 gene.

Van Steensel et al. ⁹ reported a Dutch brother and sister (patients 3 and 4) and a Belgian boy (patient 5) who had monilethrix and mutations in the KRT81 gene. The 27-year-old brother had fragile hair and alopecia, and complained of ‘rough skin’ on his upper arms and legs since childhood. Dermoscopic examination showed obvious beading of hair shafts, which was confirmed by light microscopy. He had follicular hyperkeratosis of the neck, upper arms, elbows, and upper thighs. His younger sister had a milder phenotype involving occipital balding with beading of her remaining hair, as well as slight follicular hyperkeratosis on the elbows. Their parents reportedly had normal hair but were not available for examination, and their maternal grandmother was said to have had quite short hair. The 2-year-old Belgian boy, whose mother and her twin sister were also affected, had occipital alopecia with short and brittle remaining hair, and he also exhibited follicular hyperkeratosis. Dermoscopic examination of the boy and his mother revealed beading consistent with the diagnosis of monilethrix.

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:

• The National Society of Genetic Counselors (https://www.findageneticcounselor.com/) offers a searchable directory of genetic counselors in the United States and Canada. You can search by location, name, area of practice/specialization, and/or ZIP Code.
• The American Board of Genetic Counseling (https://www.abgc.net/about-genetic-counseling/find-a-certified-counselor/) provides a searchable directory of certified genetic counselors worldwide. You can search by practice area, name, organization, or location.
• The Canadian Association of Genetic Counselors (https://www.cagc-accg.ca/index.php?page=225) has a searchable directory of genetic counselors in Canada. You can search by name, distance from an address, province, or services.
• The American College of Medical Genetics and Genomics (http://www.acmg.net/ACMG/Genetic_Services_Directory_Search.aspx) has a searchable database of medical genetics clinic services in the United States.

Monilethrix symptoms

In most cases of monilethrix, the hair is normal at birth; it may then be slowly replaced by abnormal hair during the first few months to two years of life. In some rare cases, the hair may be abnormal at birth (congenital). The hair may be sparse, dry, lusterless, and/or brittle. In addition, the hair is unusually short and breaks off before growing longer than a few inches.

Scalp hair is most frequently affected by monilethrix. The entire scalp or small areas of the scalp may be involved. In some cases, the eyelashes, eyebrows, pubic hair, and/or other body hair may also be affected. In addition, the patchy loss of hair (alopecia) is a common characteristic of this disorder. Progressive hair loss may lead to scattered bald patches or baldness.

In most cases of monilethrix, a skin condition known as perifollicular hyperkeratosis may develop. The condition is characterized by firm dark lesions (papules) covered with gray-brown scales and crusts that appear on the skin, especially the scalp.

The severity and progression of symptoms may vary greatly from case to case. In some cases, individuals with monilethrix may experience remission of the disorder for no apparent reason (spontaneously), most often during puberty or pregnancy. In other cases, the condition may remain the same throughout life or the symptoms may become progressively worse.

Monilethrix diagnosis

The diagnosis of monilethrix may be confirmed by a thorough clinical evaluation and microscopic examination of the hair. When viewed under a microscope, the hair resembles a string of evenly-spaced beads at which the hair easily breaks.

Monilethrix treatment

Unfortunately, the is no cure for monilethrix and no specific treatment exists for monilethrix. Spontaneous resolution following puberty has occurred in some cases, but the condition rarely disappears completely. In affected females, the condition improves during pregnancy. Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

While there is no recognized definitive treatment for monilethrix, oral acitretin and topical 2% minoxidil have shown good clinical and cosmetic results with continued use ¹⁰. The systemic administration of vitamins, retinoids, griseofulvin, oral contraceptives, steroids, radiation therapy, external desquamative ointments, and steroid preparations have not show impressive results ⁴.

Avoiding trauma is perhaps the most effective method of managing monilethrix. This is because from birth, the hair of individuals with monilethrix tends to have an increased susceptibility to weathering and cosmetic damage (e.g., sunlight exposure, dyeing, bleaching, perming, curling). This susceptibility to damage can prevent hair from growing to its maximum length ⁴.

Monilethrix prognosis

Monilethrix is a lifelong disease. Symptoms spontaneously regress during puberty and pregnancy, but monilethrix never disappears completely ⁷.

References

1. Healy, E., Holmes, S. C., Belgaid, C. E., Stephenson, A. M., McLean, W. H. I., Rees, J. L., Munro, C. S. A gene for monilethrix is closely linked to the type II keratin gene cluster at 12q13. Hum. Molec. Genet. 4: 2399-2402, 1995.
2. Heydt, G. E. Zur Kenntnis des Monilethrix-Syndroms. Arch. Klin. Exp. Derm. 217: 15-29, 1963.
3. Monilethrix. https://ghr.nlm.nih.gov/condition/monilethrix
4. Monilethrix. https://emedicine.medscape.com/article/1118500-overview
5. Oliveira, Elisa Fontenelle de, & Araripe, Ana Luiza Cotta de Alencar. (2015). Monilethrix: a typical case report with microscopic and dermatoscopic findings. Anais Brasileiros de Dermatologia, 90(1), 126-127. https://dx.doi.org/10.1590/abd1806-4841.20153357
6. Monilethrix. Online Mendelian Inheritance in Man (OMIM). https://omim.org/entry/158000
7. Zlotogorski, A., Marek, D., Horev, L., Abu, A., Ben-Amitai, D., Gerad, L., Ingber, A., Frydman, M., Reznik-Wolf, H., Vardy, D. A., Pras, E. An autosomal recessive form of monilethrix is caused by mutations in DSG4: clinical overlap with localized autosomal recessive hypotrichosis. J. Invest. Derm. 126: 1292-1296, 2006.
8. Winter, H., Vabres, P., Larregue, M., Rogers, M. A., Schweizer, J. A novel missense mutation, A118E, in the helix initiation motif of the type II hair cortex keratin hHb6, causing monilethrix. Hum. Hered. 50: 322-324, 2000.
9. van Steensel, M., Vreeburg, M., Urbina, M. T., Lopez, P., Morice-Picard, F., van Geel, M. Novel KRT83 and KRT86 mutations associated with monilethrix. (Letter) Exp. Derm. 24: 222-224, 2015.
10. Rossi, A., Iorio, A., Scali, E., Fortuna, M. C., Mari, E., Palese, E., Carlesimo, M. (2011). Monilethrix Treated with Minoxidil. International Journal of Immunopathology and Pharmacology, 239–242. https://doi.org/10.1177/039463201102400129