Non-syndromic Epidermal Differentiation Disorders
DISEASE CARD
| Disease group | non-syndromic Epidermal differentiation disorders (nEDD) |
|---|---|
| Subgroups |
nonsyndromic EDD (nEDD) syndromic EDD (sEDD) palmoplantar EDD (pEDD) |
| Estimated prevalence | 1:200 |
Definition
Nonsyndromic EDDs (nEDDs) are defined as disorders that primarily affect large areas of skin and adnexal structures without alterations in extracutaneous tissues resulting from the underlying genetic change.
© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists
| Functional group | Functional subgroup | New name | Previous name | MIM # | Protein affected |
|---|---|---|---|---|---|
| Structural proteins | Filaggrin-associated disorder | FLG-nEDD | Ichthyosis vulgaris | 146700 | Filaggrin |
| Keratin-associated disorders | KRT1-nEDD-epidermolytic | Epidermolytic ichthyosis, bullous congenital ichthyosiform erythroderma, epidermolytic hyperkeratosis | 113800 | Keratin 1 | |
| KRT1-nEDD-nonepidermolytic | Epidermolytic ichthyosis | 113800 | Keratin 1 | ||
| KRT1-nEDD-spiny | Ichthyosis hystrix, Curth-Macklin type | 146590 | Keratin 1 | ||
| KRT10-nEDD-annular | Annular epidermolytic ichthyosis | 620148 | Keratin 1 | ||
| KRT10-nEDD-epidermolytic | Epidermolytic ichthyosis, bullous congenital ichthyosiform erythroderma, epidermolytic hyperkeratosis | 620150 | Keratin 10 | ||
| KRT10-nEDD-nonepidermolytic | Epidermolytic ichthyosis | 620150 | Keratin 10 | ||
| KRT10-nEDD-spiny | Ichthyosis hystrix, Lambert type | 146600 | Keratin 10 | ||
| KRT10-nEDD-annular | Annular epidermolytic ichthyosis | 607602 620150 | Keratin 10 | ||
| KRT2-nEDD | Superficial epidermolytic ichthyosis | 146800 | Keratin 2 | ||
| KRT1-nEDD-mosaic | Epidermolytic nevus | 113800 | Keratin 1 | ||
| KRT2-nEDD-mosaic | 146800 | Keratin 2 | |||
| KRT10-nEDD-mosaic | 620150 | Keratin 10 | |||
| KRT16-nEDD-mosaic | 148067 | Keratin 16 | |||
| KRT83-nEDD | Erythrokeratodermia variabilis et progressiva | 617756 | Keratin 83 | ||
| KRT1-nEDD-revertant mosaic | Ichthyosis with confett | 113800 | Keratin 1 | ||
| KRT10-nEDD-revertant mosaic | 609165 | Keratin 10 | |||
| Adhesion protein-associated disorders | PERP-nEDD-AR | Erythrokeratodermia variabilis et progressiva | 619209 | Desmosomal component, p53/p63 tetraspan plasma membrane protein (PERP) | |
| CDSN-nEDD | Peeling skin syndrome | 270300 | Corneodesmosome component, Corneodesmosin | ||
| FLG2-nEDD | 618084 | Filaggrin 2 | |||
| Cell envelope precursor protein-associated disorder | CSTA-nEDD | 607936 | Cornified cell envelope component, Cystatin A | ||
| Lipid synthesis and transport | Cholesterol metabolism enzyme-associated disorders | SULT2B1-nEDD | Lamellar ichthyosis, CIE, ARCI | 617571 | Sulfotransferase family 2B member 1 (SULT2B1) |
| Mevalonate pathway enzyme-associated disorders | MVD-nEDD | Porokeratosis, disseminated (superficial) actinic porokeratosis, linear porokeratosis, porokeratosis of Mibelli | 614714 | Mevalonate pyrophosphate decarboxylase (MVD) | |
| MVK-nEDD | 175900 | Mevalonate kinase (MVK) | |||
| PMVK-nEDD | 175800 | Phosphomevalonate kinase (PMVK) | |||
| FDPS-nEDD | 134629 | Farnesyl diphosphate synthase (FDPS) | |||
| SLC17A9-nEDD | 616063 | Solute carrier family 17 member 9 (SLC17A9) | |||
| FDFT1-nEDD | 184420 | Farnesyldiphosphate farnesyltransferase 1 (FDFT1) | |||
| Ceramide synthesis and transport disorders | ALOX12B-nEDD | Lamellar ichthyosis, CIE, ARCI | 242100 | 12R-lipoxygenase (12R-LOX) | |
| ALOXE3-nEDD | 606545 | Epidermal type lipoxygenase 3 (eLOX3) | |||
| CYP4F22-nEDD | 604777 | Cytochrome P450, family 4, subfamily F, polypeptide 22 (CYP4F22) | |||
| LIPN-nEDD | 613943 | Lipase family member N (LIPN) | |||
| CERS3-nEDD | 615023 | Ceramide synthase 3 | |||
| PNPLA1-nEDD | 615024 | Patatin-like phospholipase domain-containing 1 (PNPLA1) | |||
| SDR9C7-nEDD | Lamellar ichthyosis, ARCI | 617574 | Short chain dehydrogenase/reductase family 9C member 7 (SDR9C7) | ||
| NKPD1-nEDD | Autosomal dominant lamellar ichthyosis | NTPase KAP family P-loop domain-containing protein 1 (NKPD1) | |||
| KDSR-nEDD | Erythrokeratodermia variabilis et progressiva, PERIOPTER (periorificial and ptychotropic erythrokeratoderma) syndrome | 617526 | 3-Ketodihydrosphingosine reductase (KDSR) | ||
| ABCA12-nEDD | Harlequin ichthyosis, ARCI, CIE, erythrokeratodermia variabilis et progressiva | 607800 | ATP-binding cassette transporter family A member 12 (ABCA12) | ||
| NIPAL4-nEDD | Lamellar ichthyosis, CIE, ARCI | 612281 | Magnesium transporter NIPA4 isoform 1 (NIPAL4) | ||
| SLC27A4-nEDD | Ichthyosis prematurity syndrome | 608649 | Solute carrier family 27 member 4 (Fatty acid transporter protein) | ||
| Enzyme protease and Others | Serine protease inhibitor-associated disorder | SERPINB8-nEDD | Peeling skin syndrome | 617115 | Serpin family B member 8 (SERPINB8) |
| Cell envelope forming enzyme-associated disorders | TGM1-nEDD | Lamellar ichthyosis, CIE, ARCI, self[1]healing collodion baby, bathing suit ichthyosis | 242300 | Transglutaminase 1 | |
| Other enzyme-associated disorders | CASP14-nEDD | Lamellar ichthyosis, ARCI | 617320 | Caspase-14 | |
| ASPRV1-nEDD | Autosomal dominant lamellar ichthyosis | 146750 | Retroviral-like aspartic protease 1 (ASPRV1) | ||
| KLK11-nEDD | Autosomal dominant cornification disorder | 620507 | Kallikrein-11 | ||
| Channels | Connexin-associated disorder | GJB3-nEDD | Erythrokeratodermia variabilis et progressiva | 133200 | Gap junction protein, Connexin 31 |
| GJB4-nEDD | 617524 | Gap junction protein, Connexin 30.3 | |||
| GJA1-nEDD | 617525 | Gap junction protein, Connexin 43 | |||
| Other channel protein-associated disorders | ATP2C1-nEDD | Hailey-Hailey disease, chronic benign familial pemphigus | 169600 | Secretary pathway Ca2+ ATPase 1 (SPCA1) | |
| ATP2A2-nEDD | Darier-White disease, keratosis follicularis | 124200 | Sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2 | ||
| TRPM4-nEDD | Erythrokeratodermia variabilis et progressiva | 618531 | Transient receptor potential cation channel subfamily M member 4 (TRPM4) | ||
| MiIscellaneous | CARD14-nEDD | CARD14-associated papulosquamous eruption, pityriasis rubra pilaris type V | 173200 | Caspase recruitment domain-containing protein 14 (CARD14) | |
| POMP-nEDD | Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome) | 601952 | Protease maturation protein (POMP) |
Akiyama M, Choate K, Hernandez-Martin A, Aldwin-Easton M, Bodemer C, Gostyński A, Hovnanian A, Ishida-Yamamoto A, Malovitski K, O'Toole EA, Paller AS, Schmuth M, Schwartz J, Sprecher E, Teng JMC, Granier Tournier C, Mazereeuw-Hautier J, Tadini G, Fischer J. Nonsyndromic epidermal differentiation disorders: New classification and nomenclature based on disease-associated genes leading to targeted therapy. Br J Dermatol. 2025 May 1:ljaf154. doi: 10.1093/bjd/ljaf154.