IHCM
MCID: ICH073
MIFTS: 33

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 56 58 73 36 39
Ichthyosis Histrix, Curth-Macklin Type 56 13 6
Ihcm 56 52 73
Ichthyosis Hystrix, Curth Macklin Type 52 71
Ichthyosis Hystrix of Curth-Macklin 58 29
Curth-Macklin Type Ichthyosis Hystrix 52

Characteristics:

Orphanet epidemiological data:

58
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:

56
Inheritance:
autosomal dominant


HPO:

31
ichthyosis hystrix, curth-macklin type:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

OMIM 56 146590
KEGG 36 H00707
MeSH 43 D007057
MESH via Orphanet 44 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

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79503 Definition Ichthyosis 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). Epidemiology Prevalence is unknown. Six families and sporadic cases have been reported to date. Clinical description The 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. Etiology IHCM 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 methods Diagnosis 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 diagnosis Differential 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 diagnosis Molecular prenatal diagnosis is available for affected families. Genetic counseling Transmission 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 treatment Management is symptomatic and life-long. Oral and systemic keratolytics can improve localized hyperkeratotic lesions by exfoliating and increasing the moisture of the skin. Prognosis Life 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 : 56 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)

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 abnormality of metabolism/homeostasis 31 HP:0001939
9 hyperkeratosis 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

56
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

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

26
# 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:

40
Skin

Publications for Ichthyosis Hystrix, Curth-Macklin Type

Articles related to Ichthyosis Hystrix, Curth-Macklin Type:

(show all 21)
# Title Authors PMID Year
1
In vivo studies of mutant keratin 1 in ichthyosis hystrix Curth-Macklin. 56 6
12603866 2003
2
Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix. 6 56
11286616 2001
3
Evidence against keratin gene mutations in a family with ichthyosis hystrix Curth-Macklin. 56
7504030 1993
4
The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells. 56
1740472 1992
5
Altered keratin expression in ichthyosis hystrix Curth-Macklin. A light and electron microscopic study. 56
1695499 1990
6
Electron microscopy in the early diagnosis of genetic disorders of the skin. 56
78862 1978
7
Follow-up of a family group suffering from ichthyosis hystrix type Curth-Macklin. 56
4630590 1972
8
The genetic basis of various types of ichthyosis in a family group. 56
14349943 1954
9
A novel frameshift truncation mutation in the V2 tail domain of KRT1 causes mild ichthyosis hystrix of Curth-Macklin. 61
32049370 2020
10
Infantile Hypertrophic Cardiomyopathy and Bronchopneumonia as Causes of an Unexpected Death in an 11-Month-Old Child. 61
31448665 2019
11
Effectiveness of an integrative health-care model for climacteric-stage women. 61
23113562 2013
12
Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1. 61
21844476 2011
13
Biomarkers in the age of omics: time for a systems biology approach. 61
21319991 2011
14
Integrative health care model for climacteric stage women: design of the intervention. 61
21333027 2011
15
Ichthyosis hystrix Curth-Macklin type in an African girl. 61
20415675 2009
16
Multiple sclerosis patients show a highly significant decrease in alpha band interhemispheric synchronization measured using MEG. 61
16226894 2006
17
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
18
Seborrheic distributed papules with palmoplantar hyperkeratosis--quiz case. Diagnosis: Ichthyosis hystrix, Curth-Macklin type. 61
15967930 2005
19
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
20
Lessons from disorders of epidermal differentiation-associated keratins. 61
11813882 2002
21
[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:

6 ‎‎
# 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
1
Show member pathways
11.41 KRT5 KRT1
2
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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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