EPKHE
MCID: ERY061
MIFTS: 39

Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige (EPKHE)

Categories: Blood diseases, Genetic diseases, Immune diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

MalaCards integrated aliases for Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

Name: Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige 56 29 6 39 71
Sam Syndrome 56 58 73
Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper Ige 56 73
Severe Dermatitis, Multiple Allergies, and Metabolic Wasting Syndrome 56 73
Epkhe 56 73
Congenital Erythroderma-Hypotrichosis-Recurrent Infections-Multiple Food Allergies Syndrome 58
Severe Dermatitis-Multiple Allergies-Metabolic Wasting Syndrome 58
Dermatitis, Exfoliative 43

Characteristics:

Orphanet epidemiological data:

58
severe dermatitis-multiple allergies-metabolic wasting syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
heterozygous carriers exhibit palmoplantar hyperkeratosis (see )
death in early childhood has been reported in some presumed homozygotes
two families described (last curated november 2013)


HPO:

31
erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper-ige:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases
Rare allergic disease
Rare immunological diseases


Summaries for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

UniProtKB/Swiss-Prot : 73 Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE: A syndrome characterized by severe dermatitis, multiple allergies and metabolic wasting. Clinical features include erythroderma, yellowish papules and plaques arranged at the periphery of the palms, along the fingers and over weight-bearing areas of the feet, skin erosions and scaling, and hypotrichosis. Additionally, patients manifest severe food allergies, elevated immunoglobulin E (IgE) levels and recurrent infections with marked metabolic wasting.

MalaCards based summary : Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige, also known as sam syndrome, is related to palmoplantar keratosis and hypotrichosis. An important gene associated with Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige is DSG1 (Desmoglein 1), and among its related pathways/superpathways are Keratinization and Apoptotic cleavage of cellular proteins. The drugs Brodalumab and Immunologic Factors have been mentioned in the context of this disorder. Affiliated tissues include skin, t cells and brain, and related phenotypes are ventricular septal defect and pulmonic stenosis

More information from OMIM: 615508

Related Diseases for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Diseases related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 palmoplantar keratosis 29.5 DSP DSG1
2 hypotrichosis 29.4 DSG1-AS1 DSG1
3 exfoliative dermatitis 12.0
4 short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities 11.6
5 dermatitis, atopic 11.3
6 cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis 10.2
7 dermatitis 10.2
8 erythrokeratoderma ''en cocardes'' 10.2
9 rare genetic skin disease 10.2
10 congestive heart failure 9.9
11 pemphigus gestationis 9.9 DSP DSG1
12 pemphigus 9.9 DSP DSG1
13 striate palmoplantar keratoderma 9.9 DSP DSG1
14 diffuse palmoplantar keratoderma 9.9 DSP DSG1
15 subcorneal pustular dermatosis 9.8 DSP DSG1
16 paraneoplastic pemphigus 9.8 DSP DSG1
17 autoimmune disease of skin and connective tissue 9.8 DSP DSG1
18 erythrokeratodermia variabilis et progressiva 1 9.8
19 psoriasis 14, pustular 9.8
20 erythrokeratodermia variabilis et progressiva 5 9.8
21 synostosis 9.8
22 pustulosis of palm and sole 9.8
23 lung disease 9.8
24 psoriasis 9.8
25 bronchiectasis 9.8
26 hypereosinophilic syndrome 9.8
27 pustular psoriasis 9.8
28 vesiculobullous skin disease 9.8 DSP DSG1
29 bullous skin disease 9.8 DSP DSG1
30 skin disease 9.8 DSP DSG1
31 benign chronic pemphigus 9.8 DSP DSG1
32 pemphigus vulgaris, familial 9.8 DSP DSG1
33 pachyonychia congenita 1 9.7 DSP DSG1
34 cellulitis 9.7 DSP DSG1
35 keratosis 9.6 DSP DSG1
36 castleman disease 9.5 DSP DSG1
37 bullous pemphigoid 9.4 DSP DSG1

Graphical network of the top 20 diseases related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:



Diseases related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige

Symptoms & Phenotypes for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Human phenotypes related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 ventricular septal defect 31 occasional (7.5%) HP:0001629
2 pulmonic stenosis 31 occasional (7.5%) HP:0001642
3 recurrent respiratory infections 31 HP:0002205
4 palmoplantar keratoderma 31 HP:0000982
5 psoriasiform dermatitis 31 HP:0003765
6 growth delay 31 HP:0001510
7 hypotrichosis 31 HP:0001006
8 erythroderma 31 HP:0001019
9 recurrent skin infections 31 HP:0001581
10 acantholysis 31 HP:0100792
11 hypernatremia 31 HP:0003228
12 hypergranulosis 31 HP:0025114
13 orthokeratosis 31 HP:0040162

Symptoms via clinical synopsis from OMIM:

56
Respiratory:
recurrent respiratory infections

Skin Nails Hair Hair:
hypotrichosis

Growth Other:
growth retardation

Cardiovascular Vascular:
pulmonic stenosis, mild (in some patients)

Skin Nails Hair Skin Electron Microscopy:
uneven distribution of desmosomes in upper epidermis

Laboratory Abnormalities:
severe hypernatremia in neonatal period

Skin Nails Hair Skin Histology:
psoriasiform dermatitis
alternating parakeratosis and orthokeratosis
alternating hypogranulosis and hypergranulosis
widespread acantholysis within spinous and granular layers
subcorneal and intragranular separation

Skin Nails Hair Skin:
recurrent skin infections
scaling
erosions
erythroderma, generalized congenital
hyperkeratotic yellowish papules and plaques arranged linearly on palms and fingers
more
Cardiovascular Heart:
ventricular septal defect (in some patients)

Abdomen Gastrointestinal:
esophagitis, eosinophilic (in some patients)
esophageal reflux (in some patients)

Immunology:
markedly elevated ige levels
recurrent skin and respiratory infections

Clinical features from OMIM:

615508

Drugs & Therapeutics for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Drugs for Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Brodalumab Approved, Investigational Phase 4 1174395-19-7
2 Immunologic Factors Phase 4
3 Dermatologic Agents Phase 4
4 Immunosuppressive Agents Phase 4
5
Infliximab Approved Phase 3 170277-31-3
6 Ixekizumab Approved, Investigational Phase 2 1143503-69-8
7 Interleukin-23 Phase 2
8 Antibodies, Monoclonal Phase 2
9 Immunoglobulins Phase 2
10 Antibodies Phase 2
11
Miconazole Approved, Investigational, Vet_approved 22916-47-8 4189

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Extension Study of Brodalumab in Subjects With Plaque Psoriasis (Psoriasis Vulgaris, Psoriatic Arthritis), Pustular Psoriasis (Generalized) and Psoriatic Erythroderma Completed NCT04183881 Phase 4 Brodalumab 210mg SC
2 A Pilot Study of Alefacept for the Treatment of Pityriasis Rubra Pilaris. Terminated NCT00815633 Phase 4 Alefacept
3 An Extension Study of KHK4827 in Subjects With Plaque Psoriasis (Psoriasis Vulgaris, Psoriatic Arthritis), Pustular Psoriasis (Generalized) and Psoriatic Erythroderma Completed NCT02052609 Phase 3 KHK4827 140mg SC;KHK4827 210mg SC
4 A Clinical Study of Increased Dose of TA-650 in Patients With Psoriasis Completed NCT01680159 Phase 3 TA-650
5 An Open Label Pilot Trial of Guselkumab in the Treatment of Adults With Pityriasis Rubra Pilaris (PRP) Recruiting NCT03975153 Phase 2
6 Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP) Active, not recruiting NCT03485976 Phase 2 Ixekizumab
7 A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Open-Label Maintenance Dosing Period to Evaluate the Efficacy and Safety of Secukinumab in Patients With Ichthyoses Active, not recruiting NCT03041038 Phase 2 Secukinumab;Placebo
8 Cosentyx (Secukinumab) for the Treatment of Adult Onset Pityriasis Rubra Pilaris: A Single Arm, Open-label Exploratory Trial Enrolling by invitation NCT03342573 Phase 1 Cosentyx
9 Compare the Results for the Extended Myoectomy and Standard Morrow's Myoectomy in Patients With Ventricular Obstruction of the Left Ventricular Output Unknown status NCT02492399
10 Analysis of Killer Immunoglobulin-like Receptor Transcripts Expression for the Diagnosis of Epidermotropic Cutaneous T-cell Lymphomas (Mycosis Fungoid and Sézary Syndrome) in Patients With Erythroderma or Erythematous Patches/Plaques. Completed NCT00748319

Search NIH Clinical Center for Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige

Cochrane evidence based reviews: dermatitis, exfoliative

Genetic Tests for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Genetic tests related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

# Genetic test Affiliating Genes
1 Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige 29 DSG1

Anatomical Context for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

MalaCards organs/tissues related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

40
Skin, T Cells, Brain, Heart, Lung

Publications for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Articles related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

(show all 14)
# Title Authors PMID Year
1
Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting. 61 56 6
23974871 2013
2
The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome. 61
31465738 2019
3
Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome caused by de novo mutation in the DSP gene misdiagnosed as generalized pustular psoriasis and treatment of acitretin with gabapentin. 61
31106887 2019
4
Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions. 61
31037311 2019
5
Sinobronchial allergic mycosis syndrome in an elderly male. 61
31171926 2019
6
SAM syndrome is characterized by extensive phenotypic heterogeneity. 61
29604126 2018
7
Compound heterozygosity for dominant and recessive DSG1 mutations in a patient with atypical SAM syndrome (severe dermatitis, multiple allergies, metabolic wasting). 61
27632246 2017
8
Report of Chinese family with severe dermatitis, multiple allergies and metabolic wasting syndrome caused by novel homozygous desmoglein-1 gene mutation. 61
27154412 2016
9
Whole-exome sequencing identifies novel autosomal recessive DSG1 mutations associated with mild SAM syndrome. 61
26288349 2016
10
[Homozygous desmoglein 1 gene mutations and severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome)]. 61
26169895 2015
11
Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. 61
26073755 2015
12
Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies. 61
25041099 2015
13
Genetic skin diseases related to desmosomes and corneodesmosomes. 61
24636350 2014
14
Sinobronchial allergic mycosis: the SAM syndrome. 61
12006459 2002

Variations for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

ClinVar genetic disease variations for Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DSG1 NM_001942.4(DSG1):c.49-1G>ASNV Pathogenic 88661 rs398122952 18:28906543-28906543 18:31326580-31326580
2 DSG1 NM_001942.4(DSG1):c.1861del (p.Ala621fs)deletion Pathogenic 88662 rs398122400 18:28923928-28923928 18:31343965-31343965

Expression for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Search GEO for disease gene expression data for Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige.

Pathways for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Pathways related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.41 DSP DSG1
2
Show member pathways
10.69 DSP DSG1

GO Terms for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

Cellular components related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell-cell junction GO:0005911 9.26 DSP DSG1
2 ficolin-1-rich granule membrane GO:0101003 9.16 DSP DSG1
3 cornified envelope GO:0001533 8.96 DSP DSG1
4 desmosome GO:0030057 8.62 DSP DSG1

Biological processes related to Erythroderma, Congenital, with Palmoplantar Keratoderma, Hypotrichosis, and Hyper-Ige according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neutrophil degranulation GO:0043312 9.26 DSP DSG1
2 keratinization GO:0031424 9.16 DSP DSG1
3 cell-cell adhesion GO:0098609 8.96 DSP DSG1
4 cornification GO:0070268 8.62 DSP DSG1

Sources for Erythroderma, Congenital, with Palmoplantar Keratoderma,...

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
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19 FMA
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30 HMDB
31 HPO
32 ICD10
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57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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70 Tocris
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72 UMLS via Orphanet
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