Case report: segmental form of Hailey-Hailey disease

Abstract

The article presents a clinical case of a rare segmental form of familial benign chronic pemphigus with a positive family history. Patient S., born in 2014, complained of unilateral eruptions in the area of the left retroauricular fold, left axilla, inguinal fold and labia majora on the left, plantar surface of the left foot. Eruptions were represented by erythematous foci, single blisters with serous contents, erosions, crusts. For the entire period, the patient was observed with the following diagnoses: microbial eczema, Sneddon-Wilkinson Disease, Inflammatory Linear Verrucose Epidermal Nevus. Due to the long-term relapsing course and ineffective therapy, additional examination methods were carried out – histological and genetic studies. Only after genetic testing, in which a heterozygous mutation of the ATP2C1 gene was revealed, and geneticist’s consultation, the final diagnosis was established – Hailey-Hailey Disease.
It is known, that the segmental form is formed as a result of mosaicism, which can be of two types. The term "mosaicism" refers to the presence in an organism of two or more genetically heterogeneous cell populations formed from a genetically homogeneous zygote. The formation of type 1 mosaicism is based on a de novo postzygotic mutation at an early stage of embryogenesis. In turn, type 2 mosaicism develops as a result of a postzygotic mutation against the background of an already existing prezygotic mutation. Determining the type of mosaicism by genetic testing will make it possible to assess the prognosis of the disease and the chance of transmitting this disease to offspring. 

Keywords

Case report / Chronic Benign Familial Pemphigus / segmental form / Hailey-Hailey Disease / mosaicism / genetic testing

References

[1] Hu Z., Bonifas J.M., Beech J., et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey–Hailey disease // Nat Genet. 2000 Jan. Vol. 24, N 1. P. 61–5. https://doi.org/10.1038/71701

[2] Sudbrak R., Brown J., Dobson–Stone C., et al. Hailey–Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca(2+) pump // Hum Mol Genet. 2000 Apr. Vol. 9, N 7. P. 1131–40. https://doi.org/10.1093/hmg/9.7.1131

[3] Missiaen L., Raeymaekers L., Dode L., et al. SPCA1 pumps and Hailey-Hailey disease // Biochem Biophys Res Commun. 2004 Oct. Vol. 322, N 4. P. 1204-13. https://doi.org/10.1016/j.bbrc.2004.07.128

[4] Xu Z., Zhang L., Xiao Y., et al. A case of Hailey-Hailey disease in an infant with a new ATP2C1 gene mutation // Pediatr Dermatol. 2011 Mar-Apr. Vol. 28, N. 2. P. 165-8. https://doi.org/10.1111/j.1525-1470.2010.01088.x

[5] Rogner D.F., Lammer J., Zink A., Hamm H. Darier and Hailey–Hailey disease: update 2021 // J Dtsch Dermatol Ges. 2021 Oct. Vol. 19, N. 10. P. 1478–1501. https://doi.org/10.1111/ddg.14619

[6] Poblete-Gutiérrez P., Wiederholt T., König A., et al. Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept // The Journal of clinical investigation. 2004. Vol. 114, N. 10. P. 1467–1474. https://doi.org/10.1172/JCI21791

[7] Happle R. Mosaicism in human skin. Understanding the patterns and mechanisms // Archives of dermatology. 1993. Vol. 129, N. 11. P. 1460–1470.

[8] Happle R. Segmental forms of autosomal dominant skin disorders: different types of severity reflect different states of zygosity // American journal of medical genetics. 1996. Vol. 66, N. 2. P. 241–242. https://doi.org/10.1002/(SICI)1096-8628(19961211)66:2<241::AID-AJMG24>3.0.CO;2-S

[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 // Archives of dermatology. 1997. Vol. 133, N. 12. P. 1505–1509.

[10] Asahina Y., Tahara U., Aoki S., et al. Two sporadic cases of childhood-onset Hailey-Hailey disease with superimposed mosaicism // European journal of human genetics : EJHG. 2023. Vol. 31, N. 6. P. 716–720. https://doi.org/10.1038/s41431-023-01316-w

[11] Happle R. Mosaicism in Human Skin: Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. 1st ed. Berlin : Springer, 2014. https://doi.org/10.1007/978-3-642-38765-4

[12] Higaki-Mori H., Teye K., Ishii N., et al. Elderly-onset type 1 mosaic form of Hailey-Hailey disease with a postzygotic variant in ATP2C1 // The Journal of dermatology. 2021. Vol. 48, N. 4. P. e182–e183. https://doi.org/10.1111/1346-8138.15785

[13] Nanda A., Khawaja F., Al-Sabah H., Happle R. Type 2 segmental Hailey-Hailey disease with systematized bilateral arrangement // International journal of dermatology. 2014. Vol. 53, N. 4. P. 476–478. https://doi.org/10.1111/j.1365-4632.2012.05586.x

[14] Vakilzadeh F., Kolde G. Relapsing linear acantholytic dermatosis // The British journal of dermatology. 1985. Vol. 112, N. 3. P. 349–355. https://doi.org/10.1111/j.1365-2133.1985.tb04864.x

[15] König A., Hörstez S., Vakilzadeh F., Happle R. Type 2 segmental manifestation of Hailey-Hailey disease: poor therapeutic response to dermabrasion is due to severe involvement of adnexal structures // European journal of dermatology : EJD. 2000. Vol. 10, N. 4. P. 265–268.

[16] Arora S., Arora G., Ranjan P. Relapsing linear acantholytic dermatosis in a four-year-old boy // Indian journal of dermatology, venereology and leprology. 2005. Vol. 71, N. 5. P. 351–353. https://doi.org/10.4103/0378-6323.16789

RIGHTS & PERMISSIONS

Eco-Vector