Monilethrix is a condition that affects hair growth. Its 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. People with monilethrix also have sparse hair growth (hypotrichosis) and short, brittle hair that breaks easily.

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. 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.

Monilethrix is caused by mutations in one of several genes. 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.

Normal Function

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. Desmosomes help attach cells to one another and play a role in communication between cells. The DSG4 protein is found in cells in certain regions of hair follicles, including the inner compartment of the hair strand (shaft) known as the cortex. Hair growth occurs at the hair follicle when cells divide and the hair shaft is pushed upward and extends beyond the skin.

Desmosomes provide strength to the hair and are involved in signaling between neighboring cells within the hair shaft. The DSG4 protein may play a role in communicating the signals for cells to mature (differentiate) and form the hair shaft. In addition, the DSG4 protein is found in the upper layers of the skin where it provides strength and communicates signals for the skin cells to mature.

Health Conditions Related to Genetic Changes

Autosomal recessive hypotrichosis

At least 10 mutations in the DSG4 gene have been found to cause autosomal recessive hypotrichosis, a condition that results in sparse hair growth (hypotrichosis) on the scalp, and less frequently, other parts of the body. A particular mutation that deletes a piece of genetic material in the DSG4 gene (written as Ex5_8) is a common cause of the condition in individuals of Pakistani ancestry. This mutation impairs the protein's ability to help cells attach to one another. Other DSG4 gene mutations result in the production of abnormal DSG4 proteins that cannot communicate signals between cells within hair follicles or skin. As a result, hair follicles are structurally abnormal and often underdeveloped. Irregular hair follicles alter the structure and growth of hair shafts, leading to fragile hair that breaks easily. A lack of normal DSG4 protein function may weaken the skin and contribute to the skin problems sometimes seen in individuals with autosomal recessive hypotrichosis.

Monilethrix

Mutations in the DSG4 gene have been found in people with monilethrix, a hair condition characterized by strands of hair with a beaded appearance. The hair is also short, brittle and breaks easily. The mutations associated with this condition can affect any part of the DSG4 protein, but these changes typically alter the extracellular domain, which is the region of the protein outside the cell that interacts with other cells. In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the DSG4 gene are related to the abnormality in the cortex or the beaded appearance of the hair.

It is unknown why some individuals with DSG4 gene mutations develop monilethrix and others develop autosomal recessive hypotrichosis (described above). These conditions may represent different forms of the same disorder.

Other Names for This Gene

• cadherin family member 13
• CDGF13
• CDH family member 13
• CDHF13
• desmoglein-4
• DSG4_HUMAN
• LAH

Genomic Location

Normal Function

The KRT81 gene provides instructions for making the type II hair keratin K81 protein (K81). This protein belongs to a group of proteins known as keratins, which are tough, fibrous proteins that form the structural framework of cells that make up the hair, skin, and nails. Each keratin protein partners with another keratin protein to form molecules called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the tissues and protect them from being damaged by everyday physical stresses. The K81 protein is found in cells that make up the inner compartment of the hair shaft known as the cortex, and this protein helps give hair its strength and elasticity.

Health Conditions Related to Genetic Changes

Monilethrix

At least two mutations in the KRT81 gene have been identified in people with monilethrix, a hair condition characterized by strands of hair with a beaded appearance and short, brittle hair that breaks easily. Mutations associated with this condition change a single protein building block (amino acid) in the K81 protein. The amino acid changes usually occur in a region of the K81 protein thought to be important in intermediate filament formation. In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the KRT81 gene are related to the abnormality in the cortex or the beaded appearance of the hair.

Other Names for This Gene

• ghHb1
• hair keratin K2.9
• hard keratin, type II, 1
• Hb-1
• HB1
• hHAKB2-1
• hHb1
• keratin 81, type II
• keratin, hair, basic, 1
• keratin-81
• KRT81_HUMAN
• KRTHB1
• type II hair keratin Hb1

Genomic Location

Normal Function

The KRT83 gene provides instructions for making the type II hair keratin K83 protein (K83). This protein belongs to a group of proteins known as keratins, which are tough, fibrous proteins that form the structural framework of cells that make up the hair, skin, and nails. Each keratin protein partners with another keratin protein to form molecules called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the tissues and protect them from being damaged by everyday physical stresses. The K83 protein is found in cells that make up the inner compartment of the hair shaft known as the cortex, and this protein helps give hair its strength and elasticity.

Health Conditions Related to Genetic Changes

Monilethrix

Mutations in the KRT83 gene can cause monilethrix, a hair condition characterized by strands of hair with a beaded appearance and short, brittle hair that breaks easily. Mutations associated with this condition change a single protein building block (amino acid) in the K83 protein. The amino acid changes usually occur in a region of the K83 protein thought to be important in intermediate filament formation. In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the KRT83 gene are related to the abnormality in the cortex or the beaded appearance of the hair.

Erythrokeratodermia variabilis et progressiva

MedlinePlus Genetics provides information about Erythrokeratodermia variabilis et progressiva

Other Names for This Gene

• hair keratin K2.10
• hard keratin, type II, 3
• Hb-3
• HB3
• hHb3
• K83
• keratin 83, type II
• keratin, hair, basic, 3
• keratin-83
• KRT83_HUMAN
• KRTHB3
• type II hair keratin Hb3
• type-II keratin Kb23

Genomic Location

Normal Function

The KRT86 gene provides instructions for making the type II hair keratin K86 protein (K86). This protein belongs to a group of proteins known as keratins, which are tough, fibrous proteins that form the structural framework of cells that make up the hair, skin, and nails. Each keratin protein partners with another keratin protein to form molecules called intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the tissues and protect them from being damaged by everyday physical stresses. The K86 protein is found in cells that make up the inner compartment of the hair shaft known as the cortex, and this protein helps give hair its strength and elasticity.

Health Conditions Related to Genetic Changes

Monilethrix

Several mutations in the KRT86 gene can cause monilethrix, a hair condition characterized by strands of hair with a beaded appearance and short, brittle hair that breaks easily. Mutations associated with this condition change a single protein building block (amino acid) in the K86 protein. The amino acid changes usually occur in a region of the K86 protein thought to be important in intermediate filament formation. In people with monilethrix, the cortex of the affected hair shaft appears abnormal. However, it is unclear how mutations in the KRT86 gene are related to the abnormality in the cortex or the beaded appearance of the hair.

Other Names for This Gene

• hair keratin K2.11
• hard keratin, type II, 6
• HB6
• hHb6
• K86
• keratin 86, type II
• keratin K-86
• keratin protein HB6
• keratin-86
• KRT86_HUMAN
• KRTHB6
• MNX
• type II hair keratin Hb6

Genomic Location

Monilethrix can have multiple patterns of inheritance. When the condition is caused by a mutation in one of the keratin genes, 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. In rare cases, the condition results from a new mutation in the gene and is not inherited.

When the condition 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.