MCID: ICH042
MIFTS: 28

Ichthyosis, Congenital, Autosomal Recessive 6

Categories: Genetic diseases, Skin diseases, Rare diseases, Fetal diseases

Aliases & Classifications for Ichthyosis, Congenital, Autosomal Recessive 6

MalaCards integrated aliases for Ichthyosis, Congenital, Autosomal Recessive 6:

Name: Ichthyosis, Congenital, Autosomal Recessive 6 57 75 13 73
Autosomal Recessive Congenital Ichthyosis 6 12 29 6
Arci6 57 12 75
Ichthyosis, Congenital, Autosomal Recessive, Nipal4-Related 57 75
Ichthyosis, Congenital, Autosomal Recessive, Ichthyin-Related 75
Ichthyosis, Congenital, Autosomal Recessive, Type 6 40
Ichthyosis, Congenital, Autosomal Recessive 40
Ichthyosis Congenital Autosomal Recessive 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
severity of skin symptoms may vary within families
some patients report cyclical changes in severity of symptoms


HPO:

32
ichthyosis, congenital, autosomal recessive 6:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Ichthyosis, Congenital, Autosomal Recessive 6

OMIM : 57 Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). (612281)

MalaCards based summary : Ichthyosis, Congenital, Autosomal Recessive 6, also known as autosomal recessive congenital ichthyosis 6, is related to ichthyosis, congenital, autosomal recessive 2 and ichthyosis, congenital, autosomal recessive 1. An important gene associated with Ichthyosis, Congenital, Autosomal Recessive 6 is NIPAL4 (NIPA Like Domain Containing 4). Affiliated tissues include skin, and related phenotypes are ectropion and hypohidrosis

UniProtKB/Swiss-Prot : 75 Ichthyosis, congenital, autosomal recessive 6: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.

Disease Ontology : 12 An autosomal recessive congenital ichthyosis characterized by generalized ichthyosis, hyperkeratosis, parakeratosis and moderate acanthosis that has material basis in homozygous or compound heterozygous mutation in the NIPAL4 gene on chromosome 5q33.

Related Diseases for Ichthyosis, Congenital, Autosomal Recessive 6

Diseases in the Ichthyosis family:

Ichthyosis, Congenital, Autosomal Recessive 2 Ichthyosis, Congenital, Autosomal Recessive 1
Ichthyosis, Congenital, Autosomal Recessive 4b Ichthyosis, Congenital, Autosomal Recessive 4a
Ichthyosis, Congenital, Autosomal Recessive 11 Ichthyosis, Congenital, Autosomal Recessive 5
Ichthyosis, Congenital, Autosomal Recessive 3 Ichthyosis, Congenital, Autosomal Recessive 6
Ichthyosis, Congenital, Autosomal Recessive 8 Ichthyosis, Congenital, Autosomal Recessive 7
Ichthyosis, Congenital, Autosomal Recessive 9 Ichthyosis, Congenital, Autosomal Recessive 10
Ichthyosis, Congenital, Autosomal Recessive 12 Ichthyosis, Congenital, Autosomal Recessive 14
Ichthyosis, Congenital, Autosomal Recessive 13 Autosomal Recessive Congenital Ichthyosis
Ichthyosis, Acquired

Diseases related to Ichthyosis, Congenital, Autosomal Recessive 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 ichthyosis, congenital, autosomal recessive 2 12.4
2 ichthyosis, congenital, autosomal recessive 1 12.4
3 ichthyosis, congenital, autosomal recessive 3 12.4
4 ichthyosis, congenital, autosomal recessive 8 12.4
5 ichthyosis, congenital, autosomal recessive 9 12.4
6 ichthyosis, congenital, autosomal recessive 10 12.4
7 ichthyosis, congenital, autosomal recessive 4a 12.3
8 ichthyosis, congenital, autosomal recessive 11 12.3
9 ichthyosis, congenital, autosomal recessive 5 12.3
10 ichthyosis, congenital, autosomal recessive 12 12.3
11 ichthyosis, congenital, autosomal recessive 14 12.3
12 ichthyosis, congenital, autosomal recessive 4b 12.3
13 ichthyosis, congenital, autosomal recessive 13 12.3
14 ichthyosis, congenital, autosomal recessive 7 12.1

Graphical network of the top 20 diseases related to Ichthyosis, Congenital, Autosomal Recessive 6:



Diseases related to Ichthyosis, Congenital, Autosomal Recessive 6

Symptoms & Phenotypes for Ichthyosis, Congenital, Autosomal Recessive 6

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin Histology:
hyperkeratosis
parakeratosis
acanthosis, moderate
orthohyperkeratosis (in some patients)
thickening of stratum corneum
more
Head And Neck Eyes:
ectropion (in some patients)

Skin Nails Hair Nails:
clubbing of nails (in some patients)

Skin Nails Hair Skin:
palmoplantar keratoderma
collodion membrane at birth (in some patients)
hypohidrosis (in some patients)
erythroderma (in some patients)
icthyosis, generalized
more
Skin Nails Hair Skin Electron Microscopy:
lamellae in stratum corneum with few or minimal lipid droplets
regularly elongated perinuclear membranes in stratum corneum and granulosum
vesicular complexes in stratum corneum
electron-lucent vacuoles, some containing 1 or more smaller vesicles


Clinical features from OMIM:

612281

Human phenotypes related to Ichthyosis, Congenital, Autosomal Recessive 6:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 ectropion 32 occasional (7.5%) HP:0000656
2 hypohidrosis 32 occasional (7.5%) HP:0000966
3 palmoplantar keratoderma 32 HP:0000982
4 erythroderma 32 occasional (7.5%) HP:0001019
5 parakeratosis 32 HP:0001036
6 congenital nonbullous ichthyosiform erythroderma 32 HP:0007479
7 epidermal acanthosis 32 HP:0025092

Drugs & Therapeutics for Ichthyosis, Congenital, Autosomal Recessive 6

Search Clinical Trials , NIH Clinical Center for Ichthyosis, Congenital, Autosomal Recessive 6

Genetic Tests for Ichthyosis, Congenital, Autosomal Recessive 6

Genetic tests related to Ichthyosis, Congenital, Autosomal Recessive 6:

# Genetic test Affiliating Genes
1 Autosomal Recessive Congenital Ichthyosis 6 29 NIPAL4

Anatomical Context for Ichthyosis, Congenital, Autosomal Recessive 6

MalaCards organs/tissues related to Ichthyosis, Congenital, Autosomal Recessive 6:

41
Skin

Publications for Ichthyosis, Congenital, Autosomal Recessive 6

Variations for Ichthyosis, Congenital, Autosomal Recessive 6

UniProtKB/Swiss-Prot genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 6:

75
# Symbol AA change Variation ID SNP ID
1 NIPAL4 p.Gly142Val VAR_031736 rs775903553
2 NIPAL4 p.Ala176Asp VAR_031737 rs199422217
3 NIPAL4 p.Ser208Phe VAR_031738
4 NIPAL4 p.His237Asn VAR_031739
5 NIPAL4 p.Gly297Arg VAR_031740 rs375688767
6 NIPAL4 p.Gly230Arg VAR_054120 rs370356566
7 NIPAL4 p.Ser135Arg VAR_075461

ClinVar genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 6:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NIPAL4 NM_001099287.1(NIPAL4): c.433C> T (p.Arg145Ter) single nucleotide variant Pathogenic rs199422216 GRCh37 Chromosome 5, 156890311: 156890311
2 NIPAL4 NM_001099287.1(NIPAL4): c.433C> T (p.Arg145Ter) single nucleotide variant Pathogenic rs199422216 GRCh38 Chromosome 5, 157463303: 157463303
3 NIPAL4 NIPAL4, ALA114ASN single nucleotide variant Pathogenic
4 NIPAL4 NM_001099287.1(NIPAL4): c.527C> A (p.Ala176Asp) single nucleotide variant Pathogenic rs199422217 GRCh37 Chromosome 5, 156895736: 156895736
5 NIPAL4 NM_001099287.1(NIPAL4): c.527C> A (p.Ala176Asp) single nucleotide variant Pathogenic rs199422217 GRCh38 Chromosome 5, 157468728: 157468728
6 NIPAL4 NIPAL4, IVS5, G-A, +1 single nucleotide variant Pathogenic

Expression for Ichthyosis, Congenital, Autosomal Recessive 6

Search GEO for disease gene expression data for Ichthyosis, Congenital, Autosomal Recessive 6.

Pathways for Ichthyosis, Congenital, Autosomal Recessive 6

GO Terms for Ichthyosis, Congenital, Autosomal Recessive 6

Sources for Ichthyosis, Congenital, Autosomal Recessive 6

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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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