Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Letter
ARTICLE IN PRESS
doi:
10.25259/IJDVL_77_2024

Extensive Darier disease accompanied by pterygium and scoliosis in a patient with a start codon mutation of the ATP2A2 gene

Department of Dermatology, West China Hospital of Sichuan University, Wuhou district, Guoxue alley, Sichuan
Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, China.

*Both authors contributed equally to the article.

Corresponding author: Prof. Xian Jiang, Department of Dermatology, West China Hospital of Sichuan University, Wuhou district, Guoxue alley, Chengdu, Sichuan, China. jiangxian@scu.edu.cn

Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Song D, Geng J, Yi Q, Liu H, Wang S, Jiang X. Extensive Darier disease accompanied by pterygium and scoliosis in a patient with a start codon mutation of the ATP2A2 gene. Indian J Dermatol Venereol Leprol. doi: 10.25259/IJDVL_77_2024

Dear Editor,

Darier disease (OMIM 124200) is an inherited skin condition characterised by malodorous keratotic papules, primarily affecting the seborrheic areas on the upper trunk and scalp.1 Mutations in the ATP2A2 gene are identified as the causative factors for Darier disease.1 Darier Disease is thought to be associated with extracutaneous conditions such as diabetes, heart failure and neuropsychiatric disorders.1,2 Here, we report a case of a severe Darier disease with pterygium and scoliosis, potentially linked to a start codon mutation in ATP2A2.

A 30-year-old Chinese man presented with generalised pruritic eruptions persisting for 16 years. These lesions initially developed on his scalp at the age of 14, progressively involving the face, trunk and extremities. He had a history of recurrent bacterial infections and suicidal behaviour. On examination, multiple erythematous and hyperpigmented warty papules and plaques were widely distributed on the body, predominantly on the scalp, face, trunk and extensors of all the limbs [Figures 1a, 1b and 1c]. Nail and oral mucosa were unremarkable. Anterior segment photography unveiled the presence of blepharitis and pterygium in both eyes, and corneal epithelial defects were observed under corneal fluorescein staining [Figure 1d]. X-ray of the spine revealed significant scoliosis [Figure 2]. Importantly, he reported no history of long-term weight-bearing or trauma, common risk factors for scoliosis, suggesting an atypical aetiology in this case. Histopathological study indicated papillated epidermal hyperplasia, acantholytic cleft formation and dyskeratotic cells in the epidermis [Figures 3a and 3b], leading to a diagnosis of Darier disease.

Widespread warty papules predominantly involving the trunk.
Figure 1a:
Widespread warty papules predominantly involving the trunk.
Numerous greasy papules and plaques with crusts, as well as scars on the scalp and face.
Figure 1b:
Numerous greasy papules and plaques with crusts, as well as scars on the scalp and face.
Lesions involving the extensor surfaces of the extremities.
Figure 1c:
Lesions involving the extensor surfaces of the extremities.
Noteworthy pterygium and corneal epithelial defects observed under corneal fluorescein staining.
Figure 1d:
Noteworthy pterygium and corneal epithelial defects observed under corneal fluorescein staining.
Spinal X-ray revealing significant scoliosis (red arrows).
Figure 2:
Spinal X-ray revealing significant scoliosis (red arrows).
Papillated epidermal hyperplasia, along with acantholytic cleft formation (Haematoxylin and eosin,100x).
Figure 3a:
Papillated epidermal hyperplasia, along with acantholytic cleft formation (Haematoxylin and eosin,100x).
The presence of dyskeratotic cells (Haematoxylin and eosin, 400x).
Figure 3b:
The presence of dyskeratotic cells (Haematoxylin and eosin, 400x).

Genomic DNA isolated from the proband and parents revealed a recurrent heterozygous mutation (c.1A>G, p.Met1Val) in ATP2A2, confirmed by Sanger sequencing. This mutation was absent in his unaffected parents [Figure S1]. No pathogenic mutations associated with scoliosis were identified.

ATP2A2 encodes sarcoendoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), which transports Ca2+ back into the lumen of the endoplasmic reticulum from the cytosol.1 Therefore, inherited defects in ATP2A2 occurring in Darier disease may lead to impaired regulation of the intracellular calcium signalling. Haploinsufficiency, resulting from the presence of a dysfunctional allele, is acknowledged as the molecular mechanism underpinning Darier disease.1,2 Although more than 200 ATP2A2 mutations have been documented to be associated with Darier disease, no precise genotype–phenotype correlation has been recognised to date.1,2

In this case, we describe a severe form of Darier disease with an ATP2A2 c.1A>G mutation. Interestingly, two previous reported Darier disease cases with start codon mutation also presented with widespread severe lesions.3,4 This indicates that start codon mutations may contribute to a complete haplo-insufficiency, potentially explaining severe phenotypes.

In addition to classical features, our case also presented with pterygium and scoliosis. To the best of our knowledge, these features have not been reported in Darier disease.1,2 Ophthalmic involvement in Darier disease may not be uncommon, with a survey reporting 39% of patients experiencing eye problems, predominantly manifesting as blepharitis and dry eye disease.5 Pterygium is an ocular surface disorder presenting as a raised, wedge-shaped lesion with potential implications for vision. In our case, potential mechanisms contributing to pterygium may include chronic inflammation affecting the ocular surface epithelium and the crusting of skin lesions, which could obstruct the Meibomian gland and disrupt its normal functioning.

Skeletal changes are rarely documented in Darier disease. Bone cysts and developmental retardation were found in a few cases.6,7 The aetiology of scoliosis in Darier disease remains elusive, potentially involving a spectrum of genetic and environmental factors. In our case, no known scoliosis-related mutations were found, and the patient’s history lacked known risk factors. This suggests a possible link with SERCA2’s role in calcium homeostasis affecting osteoclast survival in the skeleton, which may contribute to scoliosis.6,7 However, further experiments are needed to verify this hypothesis.

In conclusion, we identified a start codon variant in the ATP2A2 gene in this case with severe Darier disease. Our case highlights the importance of ophthalmologic and orthopaedic evaluation in Darier disease patients. The potential associations of ATP2A2 mutations with scoliosis and pterygium warrant further investigation.

Supplementary File 1

Ethical approval

The research/study was approved by the Institutional Review Board at the Biomedical Ethics Committee, West China Hospital, Sichuan University, number 2021Y-Approval-11, dated 2021/1/11.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

References

  1. , . Darier disease - A multi-organ condition? Acta Derm Venereol. 2021;101:adv00430.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  2. , , , . Impaired calcium signalling and neuropsychiatric disorders in Darier disease: An exploratory review. Exp Dermatol. 2022;31:1302-10.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , . Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability. Br J Dermatol. 2004;150:652-7.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , . 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;8:1621-30.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , . Ophthalmic Assessment in Patients With Darier Disease. Am J Ophthalmol. 2021;227:139-42.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , . Darier’s disease with changes in the bones. Int J Dermatol. 1994;33:46-7.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , , . Darier disease, multiple bone cysts, and aniridia due to double de novo heterozygous mutations in ATP2A2 and PAX6. Am J Med Genet A. 2009;149:1768-72.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views
2,202

PDF downloads
3,739
View/Download PDF
Download Citations
BibTeX
RIS
Show Sections