- Michihiro Kono, MD, PhD
Michihiro Kono, MD, PhD
- Associate Professor, Department of Dermatology
- Nagoya University Graduate School of Medicine
The dyschromatoses are a group of rare, inherited pigmentary disorders characterized by the development during infancy or childhood of numerous, irregular hyperpigmented and hypopigmented macules approximately 5 mm in diameter . Dyschromatosis symmetrica hereditaria (DSH, MIM #127400) and dyschromatosis universalis hereditaria (DUH, DUH1 MIM #127500, DUH2 MIM #612715, DUH3 MIM #615402), which are the two most common dyschromatoses, were first reported and most commonly occur in Japan.
This topic will discuss the clinical manifestations, diagnosis, and treatment of DSH and DUH. Other congenital and inherited hyperpigmentation disorders and the acquired hyperpigmentation disorders are discussed separately. (See "Acquired hyperpigmentation disorders".)
Epidemiologic data on the inherited dyschromatoses are limited. The prevalence of dyschromatosis symmetrica hereditaria (DSH) in Japan is estimated to be approximately 1.5 per 100,000 . The prevalence of dyschromatosis universalis hereditaria (DUH) is probably much lower than DSH prevalence. One study reported that approximately 1.9 and 0.3 per 100,000 dermatology consultations in Japan are related to DSH and DUH, respectively .
DYSCHROMATOSIS SYMMETRICA HEREDITARIA
Dyschromatosis symmetrica hereditaria (DSH), also called reticulate acropigmentation of Dohi, is an autosomal dominant disorder characterized by a mixture of hypopigmented and hyperpigmented macules approximately 5 mm in diameter on the dorsa of the hands and feet (picture 1) and freckle-like macules on the face. First described by Toyama in 1910, DSH has been reported mainly in Japan and China [4,5]. However, Korean , Taiwanese , Thai , Indian , Turkish , European [11,12], and Hispanic  cases have also been reported.
Genetics — DSH (MIM#127400) is caused by mutations in the adenosine deaminase acting on RNA1 gene (ADAR1) at 1q21.3, which encodes the RNA editing enzyme . DSH is inherited in an autosomal dominant manner with nearly complete penetrance but variable expressivity. Both familial and sporadic cases have been reported. More than 130 different mutations throughout ADAR1 have been described in patients with DSH. These mutations, including nonsense, missense, frameshift, and splice-site mutations, are thought to lead to ADAR1 haploinsufficiency.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:
- Urabe K, Hori Y. Dyschromatosis. Semin Cutan Med Surg 1997; 16:81.
- Miyamura Y, Suzuki T, Kono M, et al. Mutations of the RNA-specific adenosine deaminase gene (DSRAD) are involved in dyschromatosis symmetrica hereditaria. Am J Hum Genet 2003; 73:693.
- Fukai K, Oiso N, Kawaguchi M, et al. Guidelines for the diagnosis and treatment of oculo-cutaneous albinism in Japan (in Japanese). Jpn J Dermatol 2014; 124:1897.
- Toyama I. An unknown disorder of hyperpigmentation (in Japanese). Jpn J Dermatol Urol 1910; 10:644.
- Toyama I. Dyschromatosis symmetrica hereditaria (in Japanese). Jpn J Dermatol Urol 1929; 29:95.
- Kim NI, Park SA, Youn JI. Dyschromatosis symmetrica hereditaria affecting two families. Korean J Dermatol 1980; 18:585.
- Sheu HM, Yu HS. Dyschromatosis symmetrica hereditaria--a histochemical and ultrastructural study. Taiwan Yi Xue Hui Za Zhi 1985; 84:238.
- Kantaputra PN, Chinadet W, Ohazama A, Kono M. Dyschromatosis symmetrica hereditaria with long hair on the forearms, hypo/hyperpigmented hair, and dental anomalies: report of a novel ADAR1 mutation. Am J Med Genet A 2012; 158A:2258.
- Dhar S, Malakar S. Acropigmentation of Dohi in a 12-year-old boy. Pediatr Dermatol 1998; 15:242.
- Bilen N, Aktürk AŞ, Kawaguchi M, et al. Dyschromatosis symmetrica hereditaria: a case report from Turkey, a new association and a novel gene mutation. J Dermatol 2012; 39:857.
- Patrizi A, Manneschi V, Pini A, et al. Dyschromatosis symmetrica hereditaria associated with idiopathic torsion dystonia. A case report. Acta Derm Venereol 1994; 74:135.
- Ostlere LS, Ratnavel RC, Lawlor F, et al. Reticulate acropigmentation of Dohi. Clin Exp Dermatol 1995; 20:477.
- Kono M, Akiyama M, Suganuma M, et al. Dyschromatosis symmetrica hereditaria by ADAR1 mutations and viral encephalitis: a hidden link? Int J Dermatol 2013; 52:1582.
- Bass BL, Weintraub H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 1988; 55:1089.
- Rueter SM, Dawson TR, Emeson RB. Regulation of alternative splicing by RNA editing. Nature 1999; 399:75.
- Patterson JB, Samuel CE. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 1995; 15:5376.
- Wang Q, Miyakoda M, Yang W, et al. Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene. J Biol Chem 2004; 279:4952.
- Qiu W, Wang X, Buchanan M, et al. ADAR1 is essential for intestinal homeostasis and stem cell maintenance. Cell Death Dis 2013; 4:e599.
- Hartner JC, Walkley CR, Lu J, Orkin SH. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol 2009; 10:109.
- George CX, John L, Samuel CE. An RNA editor, adenosine deaminase acting on double-stranded RNA (ADAR1). J Interferon Cytokine Res 2014; 34:437.
- Patterson JB, Thomis DC, Hans SL, Samuel CE. Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons. Virology 1995; 210:508.
- Samuel CE. Adenosine deaminases acting on RNA (ADARs) are both antiviral and proviral. Virology 2011; 411:180.
- Suzuki N, Suzuki T, Inagaki K, et al. Ten novel mutations of the ADAR1 gene in Japanese patients with dyschromatosis symmetrica hereditaria. J Invest Dermatol 2007; 127:309.
- Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14:778.
- Tomita Y, Suzuki T. Genetics of pigmentary disorders. Am J Med Genet C Semin Med Genet 2004; 131C:75.
- Oyama M, Shimizu H, Ohata Y, et al. Dyschromatosis symmetrica hereditaria (reticulate acropigmentation of Dohi): report of a Japanese family with the condition and a literature review of 185 cases. Br J Dermatol 1999; 140:491.
- Kondo T, Suzuki T, Ito S, et al. Dyschromatosis symmetrica hereditaria associated with neurological disorders. J Dermatol 2008; 35:662.
- Hou Y, Chen J, Gao M, et al. Five novel mutations of RNA-specific adenosine deaminase gene with dyschromatosis symmetrica hereditaria. Acta Derm Venereol 2007; 87:18.
- Nishigori C, Miyachi Y, Takebe H, Imamura S. A case of xeroderma pigmentosum with clinical appearance of dyschromatosis symmetrica hereditaria. Pediatr Dermatol 1986; 3:410.
- Kondo T, Suzuki T, Mitsuhashi Y, et al. Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: histological observation and comparison of genotypes and clinical phenotypes. J Dermatol 2008; 35:395.
- Tojo K, Sekijima Y, Suzuki T, et al. Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a family with ADAR1 mutation. Mov Disord 2006; 21:1510.
- Shi BJ, Xue M, Liu Y, et al. First report of the coexistence of dyschromatosis symmetrica hereditaria and psoriasis: one novel TCT to A mutation in the double-RNA-specific adenosine deaminase gene. J Eur Acad Dermatol Venereol 2012; 26:657.
- Murata T, Yagi Y, Tanioka M, et al. Dyschromatosis symmetrica hereditaria with acral hypertrophy. Eur J Dermatol 2011; 21:649.
- Luo S, Zheng Y, Ni H, et al. Novel clinical and molecular findings in Chinese families with dyschromatosis symmetrica hereditaria. J Dermatol 2012; 39:556.
- Ichikawa T, Y H. A previously undescribed anomaly of pigmentation dyschromatosis universalis hereditaria. Jpn J Dermatol Urol 1933; 34:360.
- Nuber UA, Tinschert S, Mundlos S, Hauber I. Dyschromatosis universalis hereditaria: familial case and ultrastructural skin investigation. Am J Med Genet A 2004; 125A:261.
- SUENAGA M. Genetical studies on skin diseases. VII. Dyschromatosis universalis hereditaria in 5 generations. Tohoku J Exp Med 1952; 55:373.
- Udayashankar C, Nath AK. Dyschromatosis universalis hereditaria: a case report. Dermatol Online J 2011; 17:2.
- Sethuraman G, Srinivas CR, D'Souza M, et al. Dyschromatosis universalis hereditaria. Clin Exp Dermatol 2002; 27:477.
- Bukhari IA, El-Harith EA, Stuhrmann M. Dyschromatosis universalis hereditaria as an autosomal recessive disease in five members of one family. J Eur Acad Dermatol Venereol 2006; 20:628.
- Al Hawsawi K, Al Aboud K, Ramesh V, Al Aboud D. Dyschromatosis universalis hereditaria: report of a case and review of the literature. Pediatr Dermatol 2002; 19:523.
- Yusuf SM, Mijinyawa MS, Maiyaki MB, Mohammed AZ. Dyschromatosis universalis hereditaria in a young Nigerian female. Int J Dermatol 2009; 48:749.
- Kenani N, Ghariani N, Denguezli M, et al. Dyschromatosis universalis hereditaria: two cases. Dermatol Online J 2008; :16.
- Reddy SG, Worobec SM. Dyschromatosis universalis hereditaria in an African American male. Dermatol Online J 2011; 17:3.
- Stuhrmann M, Hennies HC, Bukhari IA, et al. Dyschromatosis universalis hereditaria: evidence for autosomal recessive inheritance and identification of a new locus on chromosome 12q21-q23. Clin Genet 2008; 73:566.
- An JM, Ko BJ, Cho MK, Whang KU. A Case of Sporadic Dyschromatosis Universalis Hereditaria. Ann Dermatol 2015; 27:467.
- Xing QH, Wang MT, Chen XD, et al. A gene locus responsible for dyschromatosis symmetrica hereditaria (DSH) maps to chromosome 6q24.2-q25.2. Am J Hum Genet 2003; 73:377.
- Zhang C, Li D, Zhang J, et al. Mutations in ABCB6 cause dyschromatosis universalis hereditaria. J Invest Dermatol 2013; 133:2221.
- Liu H, Li Y, Hung KK, et al. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria. PLoS One 2014; 9:e87250.
- Wang G, Li CY, Gao TW, Liu YF. Dyschromatosis universalis hereditaria: two cases in a Chinese family. Clin Exp Dermatol 2005; 30:494.
- Kim NS, Im S, Kim SC. Dyschromatosis universalis hereditaria: an electron microscopic examination. J Dermatol 1997; 24:161.
- Naveen KN, Dinesh US. Dyschromatosis universalis hereditaria with involvement of palms. Indian Dermatol Online J 2014; 5:296.
- Shono S, Toda K. Universal dyschromatosis associated with photosensitivity and neurosensory hearing defect. Arch Dermatol 1990; 126:1659.
- Kono M, Sugiura K, Suganuma M, et al. Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease. Hum Mol Genet 2013; 22:3524.
- Kono M, Suganuma M, Takama H, et al. Dowling-Degos disease with mutations in POFUT1 is clinicopathologically distinct from reticulate acropigmentation of Kitamura. Br J Dermatol 2015; 173:584.
- DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol 2012; 132:785.
- Vachiramon V, Thadanipon K, Rattanakaemakorn P. Adult-onset dyschromatoses. Clin Exp Dermatol 2012; 37:97.
- Kawakami T, Otaguchi R, Kyoya M, et al. Patient with dyschromatosis symmetrica hereditaria treated with miniature punch grafting, followed by excimer light therapy. J Dermatol 2013; 40:771.
- Nogita T, Mitsuhashi Y, Takeo C, Tsuboi R. Removal of facial and labial lentigines in dyschromatosis universalis hereditaria with a Q-switched alexandrite laser. J Am Acad Dermatol 2011; 65:e61.