MCID: ICH073
MIFTS: 32

Ichthyosis Hystrix, Curth-Macklin Type

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Ichthyosis Hystrix, Curth-Macklin Type

MalaCards integrated aliases for Ichthyosis Hystrix, Curth-Macklin Type:

Name: Ichthyosis Hystrix, Curth-Macklin Type 57 59 75 37 40
Ichthyosis Histrix, Curth-Macklin Type 57 13 6
Ichthyosis Hystrix, Curth Macklin Type 53 29 73
Ihcm 57 53 75
Curth-Macklin Type Ichthyosis Hystrix 53
Ichthyosis Hystrix of Curth-Macklin 59

Characteristics:

Orphanet epidemiological data:

59
ichthyosis hystrix of curth-macklin
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
ichthyosis hystrix, curth-macklin type:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare skin diseases


External Ids:

OMIM 57 146590
Orphanet 59 ORPHA79503
ICD10 via Orphanet 34 Q80.8
MESH via Orphanet 45 C536088
UMLS via Orphanet 74 C0432307 C1840296
MedGen 42 C1840296
MeSH 44 D007057
KEGG 37 H00707
UMLS 73 C1840296

Summaries for Ichthyosis Hystrix, Curth-Macklin Type

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79503Disease definitionIchthyosis hystrix of Curth-Macklin (IHCM) is a rare type of keratinopathic ichthyosis (see this term) that is characterized by the presence of severe hyperkeratotic lesions and palmoplantar keratoderma (PPK, see this term).EpidemiologyPrevalence is unknown. Six families and sporadic cases have been reported to date.Clinical descriptionThe skin is usually normal at birth. The disease starts in early childhood with severe hyperkeratosis of yellow-brown or grey color, and of spiky, cobblestone-like (hystrix) or verrucous appearance. Hyperkeratosis is often diffuse and more pronounced on extensor areas of the limbs, extremities and the trunk. Lesions may also be nevoid following the lines of Blaschko. Patients are also affected with striate or diffuse PPK. As the disease progresses, PPK worsens and results in deep bleeding, painful fissures and cracks. In severe cases, PPK can also lead to contractures, gangrene and loss of digits. The skin is malodorous and frequently infected. Nail dystrophy may be present. Contrary to other keratinopathic ichthyoses, no skin fragility/blister formation or erythroderma is present.EtiologyIHCM results from heterozygousframeshift mutation in a section of the KRT1 gene encoding keratin 1 (K1). These mutations lead to an abnormal supramolecular organization of keratin intermediate filaments and may be related to defects in cytoplasmic trafficking and integrity of cellular structures such as organelles and nucleus.Diagnostic methodsDiagnosis is based on clinical examination and on histological examination of skin lesion biopsies revealing papillomatous hyperplasia with hyperorthokeratosis and hypergranulosis. Electron microscopy shows keratin intermediate filaments forming continuous perinuclear shells, presence of perinuclear vacuoles and binucleate keratinocytes.Differential diagnosisDifferential diagnosis includes other forms of keratinopathic ichthyosis such as epidermolytic ichthyosis, as well as epidermolytic palmoplantar keratoderma, erythrokeratodermia variabilis, and KID syndrome (see these terms).Antenatal diagnosisMolecular prenatal diagnosis is available for affected families.Genetic counselingTransmission is autosomal dominant but some sporadic cases have been reported. The risk for an affected parent to have an affected child is of 50%.Management and treatmentManagement is symptomatic and life-long. Oral and systemic keratolytics can improve localized hyperkeratotic lesions by exfoliating and increasing the moisture of the skin.PrognosisLife expectancy is normal. However, the unaesthetic and malodorous aspects of the skin, the pain and bleeding related to PPK, and infections lead to functional disabilities and a greatly reduced quality of life.Visit the Orphanet disease page for more resources.

MalaCards based summary : Ichthyosis Hystrix, Curth-Macklin Type, also known as ichthyosis histrix, curth-macklin type, is related to palmoplantar keratosis and ichthyosis. An important gene associated with Ichthyosis Hystrix, Curth-Macklin Type is KRT1 (Keratin 1), and among its related pathways/superpathways are Keratinization and Cytoskeleton remodeling Neurofilaments. Affiliated tissues include skin, and related phenotypes are flexion contracture and recurrent skin infections

OMIM : 57 Anton-Lamprecht (1978) stated that 4 genetic disorders of keratinization were known to have a structural defect of tonofibrils. (1) In the harlequin fetus (242500), an abnormal x-ray diffraction pattern of the horn material points to a cross-beta-protein structure instead of the normal alpha-protein structure of keratin. (2) Bullous ichthyosiform erythroderma (EHK; 113800) is characterized by an early formation of clumps and perinuclear shells due to an abnormal arrangement of tonofibrils. (3) In the Curth-Macklin form of ichthyosis hystrix, concentric unbroken shells of abnormal tonofilaments form around the nucleus. (4) In ichthyosis hystrix gravior (146600), only rudimentary tonofilaments are found with compensatory production of mucous granules. (146590)

UniProtKB/Swiss-Prot : 75 Ichthyosis hystrix, Curth-Macklin type: A genodermatosis with severe verrucous hyperkeratosis. Affected individuals manifest congenital verrucous black scale on the scalp, neck, and limbs with truncal erythema, palmoplantar keratoderma and keratoses on the lips, ears, nipples and buttocks.

Related Diseases for Ichthyosis Hystrix, Curth-Macklin Type

Diseases related to Ichthyosis Hystrix, Curth-Macklin Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 palmoplantar keratosis 30.0 KRT1 KRT5
2 ichthyosis 10.7
3 osteofibrous dysplasia 9.6 KRT1 KRT5
4 skin benign neoplasm 9.6 KRT1 KRT5
5 ichthyosis bullosa of siemens 9.5 KRT1 KRT5
6 epidermolysis bullosa simplex 9.4 KRT1 KRT5
7 epidermolytic hyperkeratosis 9.3 KRT1 KRT5
8 papilloma 9.2 KRT1 KRT5
9 skin disease 9.0 KRT1 KRT5

Graphical network of the top 20 diseases related to Ichthyosis Hystrix, Curth-Macklin Type:



Diseases related to Ichthyosis Hystrix, Curth-Macklin Type

Symptoms & Phenotypes for Ichthyosis Hystrix, Curth-Macklin Type

Symptoms via clinical synopsis from OMIM:

57
Skin:
ichthyosis hystrix

Lab:
abnormal tonofibrils with formation of concentric unbroken shells of tonofilaments surrounding the nucleus on em


Clinical features from OMIM:

146590

Human phenotypes related to Ichthyosis Hystrix, Curth-Macklin Type:

59 32 (show all 9)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 flexion contracture 59 32 frequent (33%) Frequent (79-30%) HP:0001371
2 recurrent skin infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0001581
3 diffuse palmoplantar keratoderma 59 32 hallmark (90%) Very frequent (99-80%) HP:0007435
4 autoamputation of digits 59 32 occasional (7.5%) Occasional (29-5%) HP:0007460
5 ichthyosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008064
6 nail dystrophy 59 32 frequent (33%) Frequent (79-30%) HP:0008404
7 bleeding with minor or no trauma 59 32 occasional (7.5%) Occasional (29-5%) HP:0011889
8 hyperkeratosis 59 Very frequent (99-80%)
9 abnormality of metabolism/homeostasis 32 HP:0001939

GenomeRNAi Phenotypes related to Ichthyosis Hystrix, Curth-Macklin Type according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.36 KRT5
2 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.36 KRT1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-143 9.36 KRT5 KRT1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-162 9.36 KRT1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.36 KRT1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-172 9.36 KRT1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-182 9.36 KRT5
8 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.36 KRT1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-194 9.36 KRT1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-82 9.36 KRT1
11 Increased cell number in S GR00096-A 8.96 KRT1 KRT5

Drugs & Therapeutics for Ichthyosis Hystrix, Curth-Macklin Type

Search Clinical Trials , NIH Clinical Center for Ichthyosis Hystrix, Curth-Macklin Type

Genetic Tests for Ichthyosis Hystrix, Curth-Macklin Type

Genetic tests related to Ichthyosis Hystrix, Curth-Macklin Type:

# Genetic test Affiliating Genes
1 Ichthyosis Hystrix, Curth Macklin Type 29 KRT1

Anatomical Context for Ichthyosis Hystrix, Curth-Macklin Type

MalaCards organs/tissues related to Ichthyosis Hystrix, Curth-Macklin Type:

41
Skin

Publications for Ichthyosis Hystrix, Curth-Macklin Type

Articles related to Ichthyosis Hystrix, Curth-Macklin Type:

# Title Authors Year
1
Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1. ( 21844476 )
2011
2
A novel mutation and large size polymorphism affecting the V2 domain of keratin 1 in an African-American family with severe, diffuse palmoplantar keratoderma of the ichthyosis hystrix Curth-Macklin type. ( 16417221 )
2006
3
Seborrheic distributed papules with palmoplantar hyperkeratosis--quiz case. Diagnosis: Ichthyosis hystrix, Curth-Macklin type. ( 15967930 )
2005

Variations for Ichthyosis Hystrix, Curth-Macklin Type

ClinVar genetic disease variations for Ichthyosis Hystrix, Curth-Macklin Type:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 KRT1 NM_006121.3(KRT1): c.1609_1610delGGinsA (p.Gly537Ilefs) indel Pathogenic rs59169454 GRCh37 Chromosome 12, 53069302: 53069303
2 KRT1 NM_006121.3(KRT1): c.1609_1610delGGinsA (p.Gly537Ilefs) indel Pathogenic rs59169454 GRCh38 Chromosome 12, 52675518: 52675519

Expression for Ichthyosis Hystrix, Curth-Macklin Type

Search GEO for disease gene expression data for Ichthyosis Hystrix, Curth-Macklin Type.

Pathways for Ichthyosis Hystrix, Curth-Macklin Type

Pathways related to Ichthyosis Hystrix, Curth-Macklin Type according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.41 KRT1 KRT5
2
Show member pathways
10.66 KRT1 KRT5

GO Terms for Ichthyosis Hystrix, Curth-Macklin Type

Cellular components related to Ichthyosis Hystrix, Curth-Macklin Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intermediate filament GO:0005882 8.96 KRT1 KRT5
2 keratin filament GO:0045095 8.62 KRT1 KRT5

Biological processes related to Ichthyosis Hystrix, Curth-Macklin Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 keratinization GO:0031424 8.96 KRT1 KRT5
2 cornification GO:0070268 8.62 KRT1 KRT5

Sources for Ichthyosis Hystrix, Curth-Macklin Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
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44 MeSH
45 MESH via Orphanet
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54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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