What causes epidermolytic ichthyosis (EI)?

Answer

Defects in genes for keratin 1 (KRT1) and 10 (KRT10) are the cause of epidermolytic ichthyosis.^{[1, 2, 3, 4, 5]}Usually, these mutations are missense substitutions into the highly conserved alpha-helical rod and the nonhelical H1 domains of the keratin proteins.^[6]

Palmoplantar keratoderma is usually associated with KRT1 mutations; however, in rare cases, palmoplantar keratoderma may be observed in patients with KRT10 mutations.^[7]Novel mutations in both genes continue to be reported.

Patients with generalized epidermolytic ichthyosis may be born to parents with epidermolytic epidermal nevi (mosaic epidermolytic ichthyosis).^{[8, 9]}Epidermal nevi with histologic changes of epidermolytic hyperkeratosis are caused by postzygotic mutations in keratin 1 or keratin 10. If the mutation also involves gonadal cells, which is thought to be more likely in patients with more extensive cutaneous involvement, affected individuals can have offspring with generalized epidermolytic ichthyosis.

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Media Gallery

Pathology of epidermolytic ichthyosis (hematoxylin and eosin stain).
Pathology of epidermolytic ichthyosis (hematoxylin and eosin stain).
The scale in epidermolytic ichthyosis is classically described as "corrugated". Patients often experience erosions as a result of skin fragility.
The scale in epidermolytic ichthyosis is classically described as "corrugated". Patients often experience erosions as a result of skin fragility.
Palms and soles may have varying degrees of hyperkeratosis.
Hyperkeratosis involving the abdomen.
Hyperkeratosis involving the knee.

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Author

Brittany G Craiglow, MD Assistant Professor of Dermatology and Pediatrics, Yale University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Marjan Garmyn, MD, PhD Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium

Disclosure: Nothing to disclose.

Tina S Chen Twu, MD Pediatric Dermatologist/Dermatologist, Sharp Rees-Stealy Medical Group, San Diego, CA

Tina S Chen Twu, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Brandie J Metz, MD Assistant Clinical Professor of Dermatology and Pediatrics, Chief of Pediatric Dermatology, University of California, Irvine, School of Medicine

Brandie J Metz, MD is a member of the following medical societies: American Academy of Dermatology, Society for Pediatric Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Jeffrey B Smith, MD Mohs Surgery, Kaiser Permanente, San Jose, CA

Jeffrey B Smith, MD is a member of the following medical societies: American Academy of Dermatology and American College of Mohs Surgery

Disclosure: Nothing to disclose.

Sidney B Smith, MD Medical Director, Dermatologist, Dermatology, Dermacare Laser and Skin Care Clinics of Tri-Cities

Sidney B Smith, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

What causes epidermolytic ichthyosis (EI)?

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