- Keith Choate, MD, PhD
Keith Choate, MD, PhD
- Associate Professor of Dermatology, Genetics, and Pathology
- Yale University School of Medicine
The keratinopathic ichthyoses (KPI) are a group of rare cornification disorders caused by mutations in one of the keratin genes, resulting in abnormalities of the keratin intermediate filaments, a component of the keratinocyte cell cytoskeleton. KPI encompass a spectrum of clinical phenotypes of varying severity. Disorders in the KPI group include epidermolytic ichthyosis, superficial epidermolytic ichthyosis, annular epidermolytic ichthyosis, ichthyosis Curth-Macklin, and ichthyosis with confetti .
This topic will review the pathogenesis, clinical manifestations, diagnosis, and management of KPI. A general overview of the ichthyoses is presented separately. Recessive X-linked ichthyosis, Netherton syndrome, Sjögren-Larsson syndrome, and peeling skin syndrome are also discussed separately.
●(See "Recessive X-linked ichthyosis".)
●(See "Netherton syndrome".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol 2010; 63:607.
- Dreyfus I, Chouquet C, Ezzedine K, et al. Prevalence of inherited ichthyosis in France: a study using capture-recapture method. Orphanet J Rare Dis 2014; 9:1.
- Tsubota A, Akiyama M, Sakai K, et al. Keratin 1 gene mutation detected in epidermal nevus with epidermolytic hyperkeratosis. J Invest Dermatol 2007; 127:1371.
- Reddy BS, Thadeus J, Kumar SK, et al. Generalized epidermolytic hyperkeratosis in a child born to a parent with systematized epidermolytic linear epidermal nevus. Int J Dermatol 1997; 36:198.
- Akhyani M, Kiavash K, Kamyab K. Bullous ichthyosiform erythroderma in a child born to a parent with systematized linear epidermolytic hyperkeratosis. Int J Dermatol 2009; 48:215.
- Chassaing N, Kanitakis J, Sportich S, et al. Generalized epidermolytic hyperkeratosis in two unrelated children from parents with localized linear form, and prenatal diagnosis. J Invest Dermatol 2006; 126:2715.
- Kono M, Suga Y, Akashi T, et al. A Child with Epidermolytic Ichthyosis from a Parent with Epidermolytic Nevus: Risk Evaluation of Transmission from Mosaic to Germline. J Invest Dermatol 2017; 137:2024.
- Haines RL, Lane EB. Keratins and disease at a glance. J Cell Sci 2012; 125:3923.
- Zhou XM, Idler WW, Steven AC, et al. The complete sequence of the human intermediate filament chain keratin 10. Subdomainal divisions and model for folding of end domain sequences. J Biol Chem 1988; 263:15584.
- Cervantes T, Pham C, Browning JC. Superficial epidermolytic ichthyosis: a report of two families. Pediatr Dermatol 2013; 30:469.
- Steinert PM. Analysis of the mechanism of assembly of mouse keratin 1/keratin 10 intermediate filaments in vitro suggests that intermediate filaments are built from multiple oligomeric units rather than a unique tetrameric building block. J Struct Biol 1991; 107:175.
- Steinert PM, Mack JW, Korge BP, et al. Glycine loops in proteins: their occurrence in certain intermediate filament chains, loricrins and single-stranded RNA binding proteins. Int J Biol Macromol 1991; 13:130.
- Santos M, Paramio JM, Bravo A, et al. The expression of keratin k10 in the basal layer of the epidermis inhibits cell proliferation and prevents skin tumorigenesis. J Biol Chem 2002; 277:19122.
- DiGiovanna JJ, Bale SJ. Clinical heterogeneity in epidermolytic hyperkeratosis. Arch Dermatol 1994; 130:1026.
- Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol 2008; 129:705.
- Kubo Y, Urano Y, Matsuda R, et al. Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1. Arch Dermatol 2011; 147:999.
- Nayak S, Acharjya B, Mohanty P. Ichthyosis hystrix. Indian Dermatol Online J 2013; 4:47.
- Wang WH, Zhang L, Li LF, Sun TT. Ichthyosis hystrix Lambert type and Curth-Macklin type are a single entity with affected (KRT1 mutation) or unaffected (KRT10 mutation) palms and soles? Eur J Dermatol 2016; 26:493.
- Choate KA, Lu Y, Zhou J, et al. Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti. J Clin Invest 2015; 125:1703.
- Choate KA, Lu Y, Zhou J, et al. Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 2010; 330:94.
- Choate KA, Lu Y, Zhou J, et al. Ichthyosis with confetti shows widespread somatic reversion via mitotic recombination at two distinct loci. J Invest Dermatol 2011; 131:S64.
- Choate KA, Milstone LM. Phenotypic expansion in ichthyosis with confetti. JAMA Dermatol 2015; 151:15.
- Lim YH, Qiu J, Saraceni C, et al. Genetic Reversion via Mitotic Recombination in Ichthyosis with Confetti due to a KRT10 Polyalanine Frameshift Mutation. J Invest Dermatol 2016; 136:1725.
- Sahn EE, Weimer CE Jr, Garen PD. Annular epidermolytic ichthyosis: a unique phenotype. J Am Acad Dermatol 1992; 27:348.
- Joh GY, Traupe H, Metze D, et al. A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosiform erythroderma. J Invest Dermatol 1997; 108:357.
- Sybert VP, Francis JS, Corden LD, et al. Cyclic ichthyosis with epidermolytic hyperkeratosis: A phenotype conferred by mutations in the 2B domain of keratin K1. Am J Hum Genet 1999; 64:732.
- Ross R, DiGiovanna JJ, Capaldi L, et al. Histopathologic characterization of epidermolytic hyperkeratosis: a systematic review of histology from the National Registry for Ichthyosis and Related Skin Disorders. J Am Acad Dermatol 2008; 59:86.
- Mirza H, Kumar A, Craiglow BG, et al. Mutations Affecting Keratin 10 Surface-Exposed Residues Highlight the Structural Basis of Phenotypic Variation in Epidermolytic Ichthyosis. J Invest Dermatol 2015; 135:3041.
- Hirano SA, Harvey VM. From progressive symmetric erythrokeratoderma to erythrokeratoderma variabilis progressiva. J Am Acad Dermatol 2011; 64:e81.
- Boyden LM, Craiglow BG, Zhou J, et al. Dominant De Novo Mutations in GJA1 Cause Erythrokeratodermia Variabilis et Progressiva, without Features of Oculodentodigital Dysplasia. J Invest Dermatol 2015; 135:1540.
- Richard G, Smith LE, Bailey RA, et al. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat Genet 1998; 20:366.
- Macari F, Landau M, Cousin P, et al. Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis. Am J Hum Genet 2000; 67:1296.
- Boyden LM, Kam CY, Hernández-Martín A, et al. Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome. Hum Mol Genet 2016; 25:348.
- Avril M, Riley C. Management of Epidermolytic Ichthyosis in the Newborn. Neonatal Netw 2016; 35:19.
- CLINICAL PHENOTYPES
- Epidermolytic ichthyosis
- Minor variants
- - Superficial epidermolytic ichthyosis
- - Ichthyosis hystrix Curth-Macklin and ichthyosis Lambert type
- - Ichthyosis with confetti
- - Annular epidermolytic ichthyosis
- DIFFERENTIAL DIAGNOSIS
- General measures
- Topical and systemic retinoids
- SUMMARY AND RECOMMENDATIONS