Keratin deficiency, or more accurately, defects in keratin production or function due to genetic mutations, leads to a variety of skin and appendage disorders. These diseases primarily affect tissues rich in keratin, such as the skin, hair, and nails.
Keratin-Related Diseases
Mutations in keratin genes, particularly those encoding keratins expressed in the epidermis, can disrupt the structural integrity of epithelial cells, leading to fragility and abnormal tissue function. Here are some examples:
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Epidermolysis Bullosa Simplex (EBS): This is perhaps the most well-known group of diseases associated with keratin mutations. EBS is characterized by skin blistering that occurs with minor trauma. Mutations in KRT5 and KRT14, which encode keratin 5 and keratin 14 respectively, are the most common causes of EBS.
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Keratinopathic Ichthyosis (KPI): This group of ichthyoses (skin scaling disorders) is caused by mutations in keratin genes. They lead to abnormal keratinization and scaling of the skin.
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Pachyonychia Congenita (PC): This ectodermal dysplasia affects the nails, skin, hair, and oral mucosa. It's characterized by thickened nails (onychogryphosis), painful palmoplantar keratoderma, and oral leukokeratosis. PC is often caused by mutations in keratin genes KRT6A, KRT6B, KRT6C, KRT16, and KRT17.
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Monilethrix: This rare genetic hair disorder results in beaded hair due to structural defects in the hair shaft. Mutations in KRT81, KRT83, and KRT86, encoding hair keratins, cause Monilethrix.
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Steatocystoma Multiplex: This condition is characterized by the development of multiple, small cysts in the skin containing sebum. Mutations in KRT17 are often implicated.
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Ichthyosis Bullosa of Siemens (IBS): A type of epidermolytic ichthyosis characterized by blistering and scaling of the skin. IBS is typically caused by mutations in KRT2e.
Summary Table
| Disease | Key Features | Common Keratin Mutations |
|---|---|---|
| Epidermolysis Bullosa Simplex | Skin blistering with minor trauma | KRT5, KRT14 |
| Keratinopathic Ichthyosis | Skin scaling disorders | Various KRT genes |
| Pachyonychia Congenita | Thickened nails, palmoplantar keratoderma, oral leukokeratosis | KRT6A, KRT6B, KRT16, KRT17, KRT6C |
| Monilethrix | Beaded hair | KRT81, KRT83, KRT86 |
| Steatocystoma Multiplex | Multiple skin cysts containing sebum | KRT17 |
| Ichthyosis Bullosa of Siemens | Blistering and scaling of the skin | KRT2e |
It's important to note that the specific phenotype (observable characteristics) and severity of these diseases can vary depending on the specific keratin gene affected and the nature of the mutation. Genetic testing is often used to confirm the diagnosis and identify the specific mutation.
