Ichthyosis Hystrix, Curth-Macklin Type (IHCM)

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 58 73 36 39
Ichthyosis Histrix, Curth-Macklin Type 57 13 6
Ihcm 57 20 73
Ichthyosis Hystrix, Curth Macklin Type 20 71
Ichthyosis Hystrix of Curth-Macklin 58 29
Curth-Macklin Type Ichthyosis Hystrix 20


Orphanet epidemiological data:

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


57 (Updated 05-Mar-2021)
autosomal dominant


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


Orphanet: 58  
Rare skin diseases

External Ids:

OMIM® 57 146590
KEGG 36 H00707
MeSH 44 D007057
MESH via Orphanet 45 C536088
ICD10 via Orphanet 33 Q80.8
UMLS via Orphanet 72 C0432307 C1840296
Orphanet 58 ORPHA79503
MedGen 41 C1840296
UMLS 71 C1840296

Summaries for Ichthyosis Hystrix, Curth-Macklin Type

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79503DefinitionIchthyosis 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 heterozygous frameshift 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 ichthyosis and keratosis. 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 ichthyosis and diffuse palmoplantar keratoderma

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) (Updated 05-Mar-2021)

KEGG : 36 Ichthyosis hystrix, Curth-Macklin type is a rare autosomal dominant skin disorder characterized by spiky, verrucous hyperkeratosis of palms and soles. Diagnosis is supported by specific ultrastructural abnormalities such as perinuclear tonofibril shells of keratin intermediate filaments in binucleated suprabasal keratinocytes.

UniProtKB/Swiss-Prot : 73 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

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

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

58 31 (show all 9)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ichthyosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008064
2 diffuse palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0007435
3 recurrent skin infections 58 31 hallmark (90%) Very frequent (99-80%) HP:0001581
4 flexion contracture 58 31 frequent (33%) Frequent (79-30%) HP:0001371
5 nail dystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0008404
6 autoamputation of digits 58 31 occasional (7.5%) Occasional (29-5%) HP:0007460
7 bleeding with minor or no trauma 58 31 occasional (7.5%) Occasional (29-5%) HP:0011889
8 hyperkeratosis 58 Very frequent (99-80%)
9 abnormality of metabolism/homeostasis 31 HP:0001939

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skin Nails Hair Skin:
ichthyosis hystrix

Skin Nails Hair Skin Electron Microscopy:
abnormal tonofibrils with formation of concentric unbroken shells of tonofilaments surrounding the nucleus

Clinical features from OMIM®:

146590 (Updated 05-Mar-2021)

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

# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.02 KRT5
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-182 9.02 KRT5
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 9.02 KRT5
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 9.02 KRT1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.02 KRT1
6 Decreased nuclei size in G2M GR00096-A 8.65 KRT5

Drugs & Therapeutics for Ichthyosis Hystrix, Curth-Macklin Type

Interventional clinical trials:

# Name Status NCT ID Phase Drugs
1 Integrative Health Care Model for Climacteric Stage Women Completed NCT01272115

Search 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 of Curth-Macklin 29 KRT1

Anatomical Context for Ichthyosis Hystrix, Curth-Macklin Type

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


Publications for Ichthyosis Hystrix, Curth-Macklin Type

Articles related to Ichthyosis Hystrix, Curth-Macklin Type:

(show all 21)
# Title Authors PMID Year
In vivo studies of mutant keratin 1 in ichthyosis hystrix Curth-Macklin. 57 6
12603866 2003
Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix. 6 57
11286616 2001
Evidence against keratin gene mutations in a family with ichthyosis hystrix Curth-Macklin. 57
7504030 1993
The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. 57
1740472 1992
Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study. 57
1695499 1990
Electron microscopy in the early diagnosis of genetic disorders of the skin. 57
78862 1978
Follow-up of a family group suffering from ichthyosis hystrix type Curth-Macklin. 57
4630590 1972
The genetic basis of various types of ichthyosis in a family group. 57
14349943 1954
Infantile Hypertrophic Cardiomyopathy and Bronchopneumonia as Causes of an Unexpected Death in an 11-Month-Old Child. 61
31448665 2020
A novel frameshift truncation mutation in the V2 tail domain of KRT1 causes mild ichthyosis hystrix of Curth-Macklin. 61
32049370 2020
Effectiveness of an integrative health-care model for climacteric-stage women. 61
23113562 2013
Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1. 61
21844476 2011
Biomarkers in the age of omics: time for a systems biology approach. 61
21319991 2011
Integrative health care model for climacteric stage women: design of the intervention. 61
21333027 2011
Ichthyosis hystrix Curth-Macklin type in an African girl. 61
20415675 2009
Multiple sclerosis patients show a highly significant decrease in alpha band interhemispheric synchronization measured using MEG. 61
16226894 2006
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. 61
16417221 2006
Seborrheic distributed papules with palmoplantar hyperkeratosis--quiz case. Diagnosis: Ichthyosis hystrix, Curth-Macklin type. 61
15967930 2005
Evolution of dilated cardiomyopathy (DCM) from idiopathic hypertrophic cardiomyopathy (IHCM) vs. inflammatory dilated cardiomyopathy (DCMi): a rare case of sudden death in an 8-year-old boy. 61
15239350 2004
Lessons from disorders of epidermal differentiation-associated keratins. 61
11813882 2002
[A population-based study on incidence of idiopathic cardiomyopathy in Nanjing, 1985-1989]. 61
1301260 1992

Variations for Ichthyosis Hystrix, Curth-Macklin Type

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

# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KRT1 NM_006121.4(KRT1):c.1609_1610delinsA (p.Gly537fs) Indel Pathogenic 15919 rs59169454 12:53069302-53069303 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
Show member pathways
11.41 KRT5 KRT1
Show member pathways
10.66 KRT5 KRT1

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 KRT5 KRT1
2 keratin filament GO:0045095 8.62 KRT5 KRT1

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 KRT5 KRT1
2 cornification GO:0070268 8.62 KRT5 KRT1

Sources for Ichthyosis Hystrix, Curth-Macklin Type

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
70 Tocris
72 UMLS via Orphanet
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