Disadhesion of epidermal keratinocytes: A histologic clue to palmoplantar keratodermas caused by DSG1 mutations

Bergman, Reuven; Hershkovitz, Dov; Fuchs, D; Indelman, Margarita; Gadot, Yael; Sprecher, Eli

doi:10.1016/j.jaad.2009.05.016

Cited by 34 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1g,h), in agreement with previous data showing that heterozygous mutations in DSG1 can cause either striate, focal or diffuse PPK 7-9 , associated with keratinocyte disadhesion (but not frank acantholysis; Supplementary Fig. 2) 10,11 .…”

supporting

confidence: 91%

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

et al. 2013

Self Cite

View full text Add to dashboard Cite

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and play a crucial role in maintaining epidermal integrity and barrier function. SAM syndrome-causing mutations resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. The deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

show abstract

supporting

confidence: 91%

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…pseudoainhum in MDM [10], dental problems in Papillon-Lefèvre syndrome [10], hearing loss in Olmsted syndrome [11]) as well as histopathological findings (e.g. epidermolytic changes in EPPK, retained nuclei in the stratum corneum in loricrin keratoderma, keratinocytes disadhesion in keratosis palmoplantaris striata and binuclear granular cells in ichthyosis hystrix) [12,13,14,15]. Clinical assessment is thus instrumental in order to direct the subsequent laborious molecular analysis with accuracy.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of High-Resolution Multifrequency Ultrasound of the Plantar Skin in Patients with Various Types of Hereditary Palmoplantar Keratoderma

et al. 2013

View full text Add to dashboard Cite

Background: High-variable-frequency ultrasound is used as an imaging tool for various cutaneous disorders. We utilized this tool in pachyonychia congenita (PC) patients, who typically present with plantar hyperkeratosis and often severely debilitating pain, compared to patients with epidermolytic palmoplantar keratoderma (EPPK) and mal de Meleda (MDM). Objective: To ascertain the feasibility of ultrasound technology for the diagnosis of PC. Methods: The study included a total of 16 patients, 7 with PC, 5 with EPPK and 4 with MDM, who underwent ultrasound examination of the plantar skin with high-resolution multifrequency ultrasound equipment. Results: Ultrasound scans performed over the proximal and distal plantar foot calluses in PC patients demonstrated hyperechoic dots and lines within the epidermis compatible with hyperkeratosis, engorged varicose veins in the dermis and an anechoic layer interposed between the epidermis and the dermis, corresponding to blister fluid below the calluses. In contrast to PC patients, patients with MDM and EPPK demonstrated no blisters. Conclusion: PC patients, as opposed to a group of patients with MDM and EPPK, displayed subepidermal blistering beneath their calluses. This finding may help in the diagnosis of PC and in partially explaining plantar pain as part of PC symptomatology.

show abstract

“…The SAM syndrome is a rare disease characterized by congenital erythroderma, palmoplantar keratoderma, severe dermatitis, multiple allergies, elevated IgE and metabolic wasting (Table ). It is mostly due to biallelic mutations of DSG1 (Table ), encoding the desmosomal protein desmoglein 1 . In addition, a single case of SAM syndrome due to DSP mutation has been reported .…”

Section: Syndromic Palmoplantar Keratodermasmentioning

confidence: 99%

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

Guerra

Castori²,

Didona

et al. 2018

Acad Dermatol Venereol

View full text Add to dashboard Cite

Hereditary palmoplantar keratodermas (PPKs) comprise a large and heterogeneous group of disorders characterized by persistent thickening of the epidermis at palmar and plantar surfaces. Clinical and genetic features of isolated and complex PPKs have been reviewed in part I of this 2-part review. Here we focus on clinical and molecular classification of syndromic PPKs which are recognized by additional extracutaneous manifestations, in particular deafness, specific mucosal lesions, cardiomyopathy, inborn errors of metabolism, involvement of internal organs or disorders of sexual development. Other genetic diseases, which may show palmoplantar involvement, such as selected subtypes of hereditary epidermolysis bullosa, various hereditary ichthyoses and other keratinization disorders, several ectodermal dysplasias and some multisystem genetic disorders, are also briefly summarized. PPK diagnosis is based on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatological and systemic manifestations and laboratory findings. Molecular analysis is at present the gold standard to confirm the diagnosis in PPK forms due to mutations in known causative genes. No specific and curative therapy is currently available for PPKs which highly impair patients' quality of life. Topical treatments are symptomatic and offer only temporary relief. Among systemic treatments, retinoids improve disease symptoms in the majority of patients.

show abstract

Disadhesion of epidermal keratinocytes: A histologic clue to palmoplantar keratodermas caused by DSG1 mutations

Cited by 34 publications

References 29 publications

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Comparative Study of High-Resolution Multifrequency Ultrasound of the Plantar Skin in Patients with Various Types of Hereditary Palmoplantar Keratoderma

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

Contact Info

Product

Resources

About