For the first time, we describe a case of type 2 segmental Darier disease with concomitant band-like areas of healthy skin. This clinical observation gives a further hint for the understanding of type 2 segmental manifestations in autosomal dominant diseases. We had observed a 17-year-old patient with Darier disease since the age of 13 years. On the frontal aspect of his body, the lesions were found to be diffusely and rather symmetrically disseminated. On the back, however, a band-like pattern of pronounced involvement with concomitant streaks of healthy skin, both following the lines of Blaschko, was noted. Type 2 segmental manifestation of autosomal dominant disorders can be explained by the assumption that the individual carries a germline mutation that gives rise to a diffuse, nonsegmental distribution of the disease. In addition, a postzygotic mutation occurring at an early developmental stage would result in loss of heterozygosity and give rise, in a segmental area, to a homozygous or hemizygous state of the mutation. This would explain the enhanced severity of the segmental lesions. Theoretically, an early event of mitotic recombination should give rise, simultaneously, to a clone of cells that are homozygous for the corresponding wild-type allele, and for this reason paired segmental areas of either excessive or absent involvement, in the form of twin spotting, should occur on the background of an ordinary, nonsegmental phenotype, as exemplified by Happle and König in a case of epidermolytic hyperkeratosis of Brocq. These authors stated that, in autosomal dominant skin disorders, segmental areas of healthy skin will usually be difficult to recognize. This may explain why such a twin spot phenomenon has so far not been encountered in Darier disease.

Keywords:
Darier disease, Type 2 segmental involvement, Segmental zone of absent involvement, Twin spotting, Mitotic recombination
1.
Salopek TG, Krol A, Jimbow K: Case report of Darier disease localized to the vulva in a 5-year-old girl. Pediatr Dermatol 1993;10:146–148.
2.
Sakuntabhai A, Ruiz-Perez V, Carter S, Jacobsen N, Burge S, Monk S, et al: Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nat Genet 1999;21:271–277.
3.
Ruiz-Perez VL, Carter SA, Healy E, Todd C, Rees JL, Steijlen PM, et al: ATP2A2 mutations in Darier’s disease: Variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Hum Mol Genet 1999;8:1621–1630.
4.
Kreibich K: Zum Wesen der Psorospermosis Darier. Arch Dermatol Syphilol (Wien) 1906;80:367.
5.
O’Malley MP, Haake A, Goldsmith L, Berg D: Localized Darier disease: Implications for genetic studies. Arch Dermatol 1997;133:1134–1138.
6.
Plantin P, Le Noac’h E, Leroy JP, Gourcuff H: Maladie de Darier, localisée, récidivante et photo-induite suivant les lignes de Blaschko. Ann Dermatol Vénéréol 1994;121:393–395.
7.
Papadavid E, Dawber RPR: Linear Darier’s disease in a patient with recurrent carcinoma of the bladder reflects cutaneous mosaicism. J Eur Acad Dermatol Venereol 1997;9:249–252.
8.
Sakuntabhai A, Dithavat J, Burge S, Hovnanian A: Mosaicism for ATP2A2 mutations causes segmental Darier’s disease. J Invest Dermatol 2000;115:1144–1147.
9.
Happle R: A rule concerning the segmental manifestation of autosomal dominant skin disorders: Review of clinical examples providing evidence for dichotomous types of severity. Arch Dermatol 1997;133:1505–1509.
10.
Happle R: Segmentale Typ-2-Manifestation autosomal dominanter Hautkrankheiten: Entwicklung eines neuen formalgenetischen Konzeptes. Hautarzt 2001;52:283–287.
11.
Paller AS, Syder AJ, Chan YM, Yu QC, Hutton E, Tadini G, et al: Genetic and clinical mosaicism in a type of epidermal nevus. N Engl J Med 1994;331:1408–1415.
12.
Itin PH, Buechner SA: Segmental forms of autosomal dominant skin disorders: The puzzle of mosaicism. Am J Med Genet 1999;85:351–354.
13.
Happle R, Itin PH, Brun AM: Type 2 segmental Darier disease. Eur J Dermatol 1999;9:449–451.
14.
Itin PH, Büchner SA, Happle R: Segmental manifestation of Darier disease: What is the genetic background in type 1 and type 2 mosaic phenotypes? Dermatology 2000;200:254–257.
15.
Happle R, König A: Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet 1999;84:176–177.
16.
Eng AM, Brody P, Rhee HL, Bronson DM: Congenital ichthyosiform erythroderma and epidermal nevus. Int J Dermatol 1991;30:284–287.
17.
Moss C, Larkins S, Stacey M, Blight A, Farndon PA, Davison EV: Epidermal mosaicism and Blaschko’s lines. J Med Genet 1993;30:752–755.
18.
Moss C: Cytogenetic and molecular evidence for cutaneous mosaicism: The ectodermal origin of Blaschko lines. Am J Med Genet 1999;85:330–333.
19.
Arin MJ, Longley MA, Wang XJ, Roop DR: Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders. J Cell Biol 2001;152:645–649.
20.
Chester BJ, Brown L: Darier’s disease resembling linear verrucous epidermal nevus. Arch Dermatol 1959;80:625–526.
21.
Esche C, Pier A, Zumdick M, Krutmann J, Ruzicka T: Morbus Darier im Verlauf der Blaschko-Linien. Z Hautkr 1995;70:758–760.
© 2002 S. Karger AG, Basel
2002
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