Zusammenfassung
In diesem Kapitel sollen eine Reihe monogener Erkrankungen besprochen werden, bei denen genetische Ursachen ein definiertes klinisches Krankheitsbild und bestimmte pathologische Veränderungen oder Reaktionsmuster verursachen. Die molekulare Aufklärung vieler Genodermatosen hat zu ihrer Reklassifizierung geführt, die in Ihren Ansätzen aber noch der traditionellen, an klinischen Entitäten orientierten Einteilung folgt. Entscheidend für die gezielte Diagnose von Genodermatosen sind die Familienanmnese, das klinischen Bild, die Histologie, manchmal auch Immunhistochemie, Laborchemische Untersuchungen, seltener die Elektronenmikrokopie. In bestimmten Fällen kann auf genetische Untersuchungen nicht verzichtet werden. Genodermatosen müssen genau abgeklärt werden, um das Risko assoziierter Erkrankungen an inneren Organen bei syndromischen Formen einschätzen und eine genetische Beratung einleiten zu können. Hilfestellung bieten spezielle Netzwerke (www.netzwerk-ichthyose.de und www.netzwerk-eb.de).
Similar content being viewed by others
Weiterführende Literatur
Weiterführende Literatur zu Ichthyosen
Aten E, Brasz LC, Bornholdt D et al (2010) Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2. Hum Mutat 31:1125–1133
Avshalumova L, Fabrikant J, Koriakos A (2014) Overview of skin diseases linked to connexin gene mutations. Int J Dermatol 53:192–205
Braverman N, Lin P, Moebius FF et al (1999) Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase cause X-linked dominant Conradi-Hünermann syndrome. Nat Genet 22:291–294
Chavanas S, Bodemer C, Rochat A et al (2000) Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 25:141–142
Choate KA, Lu Y, Zhou J et al (2010) Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 330:94–97
Davies MG, Marks R, Dykes PJ (1977) Epidermal abnormalities in Refsum’s disease. Br J Dermatol 97:401–406
Dale BA, Holbrook KA, Fleckman P et al (1990) Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules. J Invest Dermatol 94:6–18
De Laurenzi V, Rogers GR, Hamrock DJ et al (1996) Sjögren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nat Genet 12:52–57
Elias PM, Williams ML, Crumrine D (2010) Ichthyoses, clinical, biochemical, pathogenic and diagnostic assessment. In: Itin P (Hrsg) Current problems in dermatology, Bd 39. Karger, Basel
Easton JA, Donnelly S, Kamps MA et al (2012a) Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations. J Invest Dermatol 132:2184–2191
Fischer J, Lefèvre C, Morava E et al (2007) The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nat Genet 39:28–30
Happle R, Koch H, Lenz W (1980) The CHILD syndrome. Congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Eur J Pediatr 134:27–33
Has C, Bruckner-Tuderman L, Müller D (2000) The Conradi-Hünermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism. Hum Mol Genet 9:1951–1955
Huber M, Rettler I, Bernasconi K et al (1995) Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267:525–528
Joh GY, Traupe H, Metze D et al (1997) A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosiform erythroderma. J Invest Dermatol 108:357–361
König A, Happle R, Bornholdt D et al (2000) Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet 90:339–346
Kolde G, Happle R, Traupe H (1985) Autosomal-dominant lamellar ichthyosis: ultrastructural characteristics of a new type of congenital ichthyosis. Arch Dermatol Res 278:1–5
Krug M, Oji V, Traupe H et al (2009a) Ichthyoses – part 1: differential diagnosis of vulgar ichthyoses and therapeutic options. J Dtsch Dermatol Ges 7:511–519
Krug M, Oji V, Traupe H et al (2009b) Ichthyoses-part 2: congenital ichthyoses. J Dtsch Dermatol Ges 7:577–588
Kütting B, Traupe H (1995) Der erworbene Ichthyosis-ähnliche Hautzustand. Hautarzt 46:836–840
Metze D (2012) Disorders of Keratinization In: Calonje E, Brenn T, Lazar A (Hrsg) McKee’s pathology of the skin: with clinical correlations, Bd 1, Kap. 3. Elsevier Saunders, Philadelphia, S 46–98
Morice-Picard F, Cario-André M, Rezvani H et al (2009) New clinico-genetic classification of trichothiodystrophy. Am J Med Genet A 149A:2020–2030
Oeffner F, Fischer G, Happle R et al (2009) IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response. Am J Hum Genet 84:459–467
Oji V, Eckl KM, Aufenvenne K et al (2010a) Loss of corneodesmosin leads to severe skin barrier defect, pruritus, and atopy: unraveling the peeling skin disease. Am J Hum Genet 87:274–281
Oji V, Tadini G, Akiyama M et al (2010b) Revised nomenclature and classification of inherited ichthyoses: results of the first ichthyosis consensus conference in Sorèze 2009. J Am Acad Dermatol 63:607–641
Oji V, Metze D, Traupe H (2014) Mendelian disorders of cornification and acquired forms. In: Rook A, Wilkinson DS, Ebling FJG (Hrsg) Textbook of dermatology. Blackwell Science, Oxford, Kap 34 (im Druck)
Paige DG, Emilion GG, Bouloux PM et al (1994) A clinical and genetic study of X-linked recessive ichthyosis and contiguous gene defects. Br J Dermatol 131:622–629
Raghunath M, Hennies HC, Velten F et al (1998) A novel in situ method for the detection of deficient transglutaminase activity in the skin. Arch Dermatol Res 290:621–627
Richard G (2004) Molecular genetics of the ichthyoses. Am J Med Genet C Semin Med Genet 131C:32–44
Rothnagel JA, Dominey AM, Dempsey LD et al (1992) Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science 257:1128–1130
Rothnagel JA, Traupe H, Wojcik S et al (1994) Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens. Nat Genet 7:485–490
Sprecher E, Ishida-Yamamoto A, Becker OM et al (2001) Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix. J Invest Dermatol 116:511–519
Traupe H (1989) The ichthyoses. A guide to clinical diagosis, genetic counseling, and therapy. Springer, Berlin, S 103–138
Traupe H, Kolde G, Hamm H et al (1986) Ichthyosis bullosa of Siemens: a unique type of epidermolytic hyperkeratosis. J Am Acad Dermatol 14:1000–1005
van Geel M, van Steensel MA, Küster W et al (2002) HID and KID syndromes are associated with the same connexin 26 mutation. Br J Dermatol 146:938–942
van Steensel MA, Oranje AP, van der Schroeff JG et al (2009) The missense mutation G12D in connexin30.3 can cause both erythrokeratodermia variabilis of Mendes da Costa and progressive symmetric erythrokeratodermia of Gottron. Am J Med Genet A 149A:657–661
Weiterführende Literatur zu hereditären Palmoplantarkeratosen
Armstrong DK, McKenna KE, Purkis PE et al (1999) Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma. Hum Mol Genet 8:143–148
Bergman R, Hershkovitz D, Fuchs D et al (2010) Disadhesion of epidermal keratinocytes: a histologic clue to palmoplantar keratodermas caused by DSG1 mutations. J Am Acad Dermatol 62:107–113
Blaydon DC, Etheridge SL, Risk JM et al (2012) RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet 90:340–346
Braun-Falco M (2009) Hereditäre Palmoplantarhyperkeratosen. J Dtsch Dermatol Ges 7:971–985
Feinstein A, Friedman J, Schewach-Millet M (1998) Pachyonychia congenita. J Am Acad Dermatol 19:705–711
Fischer J, Bouadjar B, Heilig R et al (2001) Mutations in the gene encoding SLURP-1 in Mal de Meleda. Hum Mol Genet 10:875–880
Giehl KA, Eckstein GN, Pasternack SM (2012) Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am J Hum Genet 91:754–759
Guerriero C, Albanesi C, Girolomoni G (2000) Huriez syndrome: case report with a detailed analysis of skin dendritic cells. Br J Dermatol 143:1091–1096
Hamm H, Traupe H, Bröcker EB (1996) The scleroatrophic syndrome of Huriez: a cancer-prone genodermatosis. Br J Dermatol 134:512–518
Itin PH, Fistarol SK (2005) Palmoplantar keratodermas. Clin Dermatol 23:15–22
Kabashima K, Sakabe J, Yamada Y et al (2008) „Nagashima-type“ keratosis as a novel entity in the palmoplantar keratoderma category. Arch Dermatol 144:375–379
Kimonis V, DiGiovanna JJ, Yang JM et al (1994) A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma. J Invest Dermatol 103:764–769
Korge BP, Ishida-Yamamoto A, Pünter C et al (1997) Loricrin mutation in Vohwinkel’s keratoderma is unique to the variant with ichthyosis. J Invest Dermatol 109:604–610
Küster W, Becker A (1992) Indication for the identity of palmoplantar keratoderma type Unna-Thost with type Vörner. Thost’s family revisited 110 years later. Acta Derm Venereol 72:120–122
Küster W, Zehender D, Mensing H et al (1995) Keratosis palmoplantaris diffusa Vörner – Klinische, formalgenetische und molekularbiologische Untersuchungen bei 22 Familien. Hautarzt 46:705–710
Lucker GP, van de Kerkhof PC, Steijlen PM (1994) The hereditary palmoplantar keratoses: an updated review and classification. Br J Dermatol 131:1–14
Maestrini E, Monaco AP, McGrath JA (1996) A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel’s syndrome. Nat Genet 13:70–77
Maestrini E, Korge BP, Ocana-Sierra J et al (1999) A missense mutation in connexin 26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel’s syndrome) in three unrelated families. Hum Mol Genet 8:1237–1243
McLean WH, Hansen CD, Eliason MJ (2011) The phenotypic and molecular genetic features of pachyonychia congenita. J Invest Dermatol 131:1015–1017
Metze D (2012) Disorders of Keratinization In: Calonje E, Brenn T, Lazar A (Hrsg) McKee’s pathology of the Skin: with clinical correlations, Bd 1, Kap 3. Elsevier Saunders. Philadelphia, S 46–98
Norgett EE, Hatsell SJ, Carvajal-Huerta L et al (2000) Recessive mutation in desmoplakin disrupts desmoplakin–intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 9:2761–2766
Oji V, Metze D, Traupe H (2014) Mendelian disorders of cornification and acquired forms. In: Rook A, Wilkinson DS, Ebling FJG (Hrsg) Textbook of dermatology. Blackwell Science, Kap 34. Oxford (im Druck)
Rongioletti F, Betti R, Crosti C et al (1994) Marginal papular acrokeratodermas: a unified nosography for focal acral hyperkeratosis, acrokeratoelastoidosis and related disorders. Dermatology 188:28–31
Roth W, Penneys NS, Fawcett N (1978) Hereditary painful callosities. Arch Dermatol 114:591–592
Smith FJ, Corden LD, Rugg EL et al (1997) Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex. J Invest Dermatol 108:220–223
Weiterführende Literatur zu Morbus Darier
Burge-SM WJD (1992) Darier-white disease: a review of the clinical features in 163 patients. J Am Acad Dermatol 27:40–50
Bergman R, Sezin T, Indelman M et al (2012) Acrokeratosis verruciformis of Hopf showing P602L mutation in ATP2A2 and overlapping histopathological features with Darier disease. Am J Dermatopathol 34:597–601
Derrick EK, Darley CR, Burge S (1995) Comedonal Darier. Br J Dermatol 132:453–455
DiMaio DJM, Cohen PR (1998) Incidental focal acantholytic dyskeratosis. J Am Acad Dermatol 38:243–237
Itin PH, Büchner SA, Happle R (2000) Segmental manifestation of Darier disease. What is the genetic background in type 1 and type 2 mosaic phenotypes? Dermatology 200:254–257
Leverkus M, Rose C, Bröcker EB, Hamm H (1999) Intertriginöse akantholytische Dyskeratose. Hautarzt 50:733–738
Panja RK (1972) Acrokeratosis verruziformis Hopf-a clinical entitity? Br J Dermatol 96:643–651
Regazzini R, Zambruno G, DeFilippi C, Rosso R, Donadini A (1996) Isolated acral Darier's disease with hemorrhagic lesions in a kindred. Br J Dermatol 153:489–490
Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, Smith M, Munro CS, O'Donovan M, Craddock N, Kucherlapati R, Rees JL, Owen M, Lathrop GM, Monaco AP, Strachan T, Hovnanian A (1999) Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 21:271–277
Telfer NR, Burge SM, Ryan TJ (1990) Vesiculo-bullous Darier's disease. Br J Dermatol 122:831–834
Weiterführende Literatur zu Porokeratosis
Chernosky ME (1986) Porokeratosis. Arch Dermatol 122:896–870
Ito M, Fujiwara H, Maruyama T et al (1991) Morphogenesis of the cornoid lamella: histochemical, immunohistochemical, and ultrastructural study of porokeratosis. J Cutan Pathol 18:247–256
Kanzaki T, Miwa N, Kobayashi T et al (1992) Eruptive pruritic papular porokeratosis. J Dermatol 19:109–112
Kossard S, Freeman S (1990) Reticular erythema with ostial porokeratosis. J Am Acad Dermatol 22:913–916
Kutzner H, Rütten A, Hügel H (1996) Peppered pattern of cornoid lamellation: a clue to porokeratosis. Dermatopathol Pract Conceptual 2:55–56
Lucker GP, Happle R, Steijlen PM (1995) An unusual case of porokeratosis involving the natal cleft: porokeratosis ptychotropica? Br J Dermatol 132:150–151
Magee JW, McCalmont TH, LeBoit PE (1994) Overexpression of p53 tumor suppressor protein in porokeratosis. Arch Dermatol 130:187–190
Nelson C, Cowper S, Morgan M (1999) p53, mdm-2, and p21 waf-1 in the porokeratoses. Am J Dermatopathol 21:420–425
Rongioletti F, Rebora A (2002) Disseminated porokeratosis with fatal metastatic squamous cell carcinoma: an additional case of „malignant disseminated porokeratosis“. Am J Dermatopathol 24:144–148
Wade TR, Ackerman AB (1980) Cornoid lamellation. A histologic reaction pattern. Am J Dermatopathol 2:5–15
Walsh SN, Hurt MA, Santa Cruz DJ (2007) Porokeratoma. Am J Surg Pathol 31:1897–1901
Weiterführende Literatur zum epidermalen Nävus
Altman J, Mehregan AH (1971) Inflammatory linear verrucous epidermal nevus. Arch Dermatol 104:385–389
Easton JA, Donnelly S, Kamps MA et al (2012b) Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations. J Invest Dermatol 132:2184–2191
Goddard DS, Rogers M, Frieden IJ et al (2009) Widespread porokeratotic adnexal ostial nevus: clinical features and proposal of a new name unifying porokeratotic eccrine ostial and dermal duct nevus and porokeratotic eccrine and hair follicle nevus. J Am Acad Dermatol 61:1060–10694
Happle R, Rogers M (2002) Epidermal neavi. Adv Dermatol 8:175–202
Hofer T (2006) Does inflammatory linear verrucous epidermal nevus represent a segmental type 1/type 2 mosaic of psoriasis? Dermatology 212:103–107
Weiterführende Literatur zu Akanthosis nigricans
Schwarz RA (1994) Acanthosis nigricans. J Am Acad Dermatol 31:1–19
Weiterführende Literatur zu Papillomatosis confluens et reticularis Gougerot Carteaud
Kretzschmar L, Metze D, Vehring KH et al (1996) Papillomatosis confluens et reticularis. Hautarzt 47:209–213
Lee SH, Choi EH, Lee WS, Kang D et al (1991) Confluent and reticulated papillomatosis: a clinical, histopathological and electron microscopicy study. J Dermatol 18:725–730
Thoms KM, Thoms S, Bertsch HP, Emmert S (2006) Zwei Brüder mit bräunlichen, netzartigen Hyperpigmentierungen. JDDG 4:582–585
Weiterführende Literatur zu multiple minute digitate hyperkeratoses, minute aggregate keratoses und waxy keratoses of childhood
Balus L, Donati P, Amantea A, Breathnach AS (1988) Multiple minute digitate hyperkeratosis. J Am Acad Dermatol 18:431–426
Coleman R, Malone M, Handfield-Jones S (1994) Waxy keratoses of childhood. Clin Exp Dermatol 9:173–176
Nedwich JA, Sullivan JJ (1987) Disseminated spiked hyperkeratosis. Int J Dermatol 26:358–361
Paul C, Fermand J-P, Flageul B et al (1995) Hyperkeratotic spicules and monoclonal gammopathy. J Am Acad Dermatol 33:346–351
Weiterführende Literatur zur granulären Parakeratose
Chang MW, Kaufmann JM, Sj O et al (2004) Infantile granular parakeratosis: recognition of two patterns. J Am Acad Dermatol 50:S93–S96
Mehregan DA, Thomas JE, Mehregan DR (1998) Intertriginous granular parakeratosis. J Am Acad Dermatol 29:495–496
Metze D, Rütten A (1999) Granular parakeratosis – a unique acquired disorder of keratinization. J Cutan Pathol 26:339–352
Northcutt AD, Nelson DM, Tschen JA (1991) Axillary granular parakeratosis. J Am Acad Dermatol 24:541–544
Resnik K, DiLeonardo M (2003) Follicular granular parakeratosis. Am J Dermatopathol 25:428–429
Resnik K, Kantor GR, DiLeonardo M (2004) Dermatophyte-related granular parakeratosis. Am J Dermatopathol 26:70–71
Scheinfeld NS, Mones J (2005) Granular parkeratosis: pathologic and clinical correlation of 18 cases of granular parakeratosis. J Am Acad Dermatol 52:863–867
Weiterführende Literatur zu Morbus Dowling-Degos
Hanneken S, Rütten A, Eigelshoven S et al (2011) Galli-Galli disease: clinical and histopathological investigation using a case series of 18 patients. Hautarzt 62:842–851
Müller CS, Tremezaygues L, Pföhler C et al (2012) The spectrum of reticulate pigment disorders of the skin revisited. Eur J Dermatol 22:596–604
Rebora A, Crovato F (1984) The spectrum of Dowling-Degos disease. Br J Dermatol 110:627–630
Schiller M, Kütting B, Metze D (1999) Umschriebene retikuläre Hyperpigmentierungen – ein weites klinisches Spektrum. Hautarzt 50:580–585
Weiterführende Literatur zu Mobus Flegel
Metze D, Lübke D, Luger T (2000) Hyperkeratosis lenticularis perstans (M. Flegel) – Eine komplexe Differenzierungsstörung der Epidermis mit therapeutischem Ansprechen auf ein synthetisches Vitamin-D3 Derivat. Hautarzt 51:31–35
Zimmermann R (2001) 40 Jahre Morbus Flegel (Hyperkeratosis lenticularis perstans). Hautarzt 52:231–235
Weiterführende Literatur zur familiären dyskeratotischen Komedonen
Carneiro SJC, Dickson JE, Knox JM (1972) Familial dyskeratotic comedones. Arch Derm 105:249–251
Ständer S, Rütten A, Metze D (2001) Familiäre dyskeratotische Komedonen – eine seltene Entität. Hautarzt 52:533–536
Weiterführende Literatur zu umschriebener palmoplantarer Hypokeratosis
Perez A, Rutten A, Gold R et al (2002) Circumscribed palmar or plantar hypokeratosis: a distinctive epidermal malformation of the palms or soles. J Am Acad Dermatol 47:21–27
Weiterführende Literatur zu kongenitalen Poikilodermien
Drachtman RA, Alter BP (1992) Dyskeratosis congenita: clinical and genetic heterogeneity. Am J Ped Hematol/Oncol 14:297–304
Pickenäcker A, Hildebrand A, Schmid M et al (1998) Poikilodermie mit warzigen Hyperkeratosen. Hautarzt 49:586–590
Wang LL, Levy ML, Lewis RA et al (2001) Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 102:11–17
Weiterführende Literatur zu ektodermalen Dysplasien
Katz SI, Penneys NS (1971) Sebaceous gland papules in anhidrotic ectodermal dysplasia. Arch Dermatol 103:507–509
Lamartine J, Essenfelder GM, Kibar Z et al (2000) Mutations in GJB6 cause hidrotic epidermal dysplasia. Nat Genet 26:142–144
Lambert WC, Bilinski DL (1983) Diagnostic pitfalls in anhidrotic ectodermal dysplasia: indications for palmar skin biopsy. Cutis 31:182–187
Reddy BSN, Chandra S, Jha PK, Singh G (1978) Anhidrotic ectodermal dysplasia. Int J Dermatol 17:129–141
Solomon LM, Fretzin D, Pruzansky S (1970) Pilosebaceous dysplasia in the oral-facial-digital syndrome. Arch Dermatol 102:598–602
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Metze, D., Traupe, H. (2015). Hereditäre Verhornungsstörungen und epidermale Fehlbildungen. In: Cerroni, L., Garbe, C., Metze, D., Kutzner, H., Kerl, H. (eds) Histopathologie der Haut. Springer Reference Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44367-5_20-1
Download citation
DOI: https://doi.org/10.1007/978-3-662-44367-5_20-1
Received:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Online ISBN: 978-3-662-44367-5
eBook Packages: Springer Referenz Medizin