ILVASC
MCID: ICH026
MIFTS: 36

Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis (ILVASC)

Categories: Genetic diseases, Liver diseases, Rare diseases, Skin diseases

Aliases & Classifications for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

MalaCards integrated aliases for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

Name: Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis 57 20 13 39 70
Neonatal Ichthyosis-Sclerosing Cholangitis Syndrome 57 20 58 29 6
Nisch Syndrome 57 20 58 72
Ilvasc 57 20 72
Ichthyosis-Sclerosing Cholangitis Syndrome 57 20
Ichthyosis with Leukocyte Vacuoles, Alopecia and Sclerosing Cholangitis 72
Ichthyosis-Hypotrichosis-Sclerosing Cholangitis Syndrome 58
Neonatal Ichthyosis-Sclerosing Cholangitis Syndrome 36
Ichthyosis-Sclerosing Cholangitis Neonatal Syndrome 72
Nisch 72
Ihsc 58

Characteristics:

Orphanet epidemiological data:

58
neonatal ichthyosis-sclerosing cholangitis syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare hepatic diseases
Rare skin diseases


Summaries for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 59303 Definition Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome ) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. Epidemiology Less than ten patients (from unrelated consanguineous Moroccan families and from Sweden) have been reported so far. Clinical description The ichthyosis presents with diffuse white scales sparing the skin folds, and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly, and biochemical cholestasis. Overall, the clinical picture mimics biliary atresia (see this term). Portal hypertension, patent extrahepatic bile duct obstruction and splenomegaly may also be present. Histology shows extensive fibrosis and bile duct proliferation. Leukocyte vacuolization is a common finding. The hepatic disease may have variable expressivity, ranging from a progressive disease resulting in liver failure to regression of cholestasis. Etiology NISCH syndrome is caused by a mutation in the CLDN1 gene coding for the tight junction protein claudin-1. Diagnostic methods Diagnosis is based on clinical, biochemical and histological features. Differential diagnosis The differential diagnosis should include Dorfman-Chanarin syndrome and other syndromic forms of ichthyosis (see these terms). Genetic counseling NISCH syndrome shows an autosomal recessive pattern of inheritance. Management and treatment Treatments aim at improving symptoms and survival. Liver transplant remains the only effective treatment in case of liver failure. Ichthyosis is managed by hydration of the skin (topical application of creams and emollient oils), retinoids and sunlight exposure.

MalaCards based summary : Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis, also known as neonatal ichthyosis-sclerosing cholangitis syndrome, is related to ichthyosis and sclerosing cholangitis, and has symptoms including icterus An important gene associated with Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis is CLDN1 (Claudin 1), and among its related pathways/superpathways are Cell adhesion molecules and Tight junction. Affiliated tissues include liver, and related phenotypes are splenomegaly and hepatomegaly

KEGG : 36 Neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome is an autosomal recessive liver disease caused by mutations of Claudin-1, a tight-junction protein expressed in liver and skin. Patients present epidermal scaling, pruritus, and neonatal cholestatic jaundice. Alopecia is also seen and cholestasis often progresses to sclerosing cholangitis.

UniProtKB/Swiss-Prot : 72 Ichthyosis-sclerosing cholangitis neonatal syndrome: A rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, mild diffuse ichthyosis, sclerosing cholangitis and leukocyte vacuolization.

More information from OMIM: 607626

Related Diseases for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Diseases related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 ichthyosis 29.6 CLDN16 CLDN1
2 sclerosing cholangitis 29.5 CLDN16 CLDN1
3 cholangitis 29.4 CLDN16 CLDN1
4 cholestasis, benign recurrent intrahepatic, 1 11.0
5 aplasia of lacrimal and salivary glands 10.9
6 cholestasis, progressive familial intrahepatic, 1 10.9
7 microphthalmia, syndromic 10 10.9
8 cholestasis, progressive familial intrahepatic, 4 10.9
9 leber plus disease 10.9
10 nasal cavity lymphoma 10.9
11 liver disease 10.3
12 alopecia 10.2
13 hypotrichosis 10.1
14 cholestasis 10.1
15 autosomal recessive disease 10.0
16 ovarian cancer 9.9
17 lung cancer 9.9

Graphical network of the top 20 diseases related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:



Diseases related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis

Symptoms & Phenotypes for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Human phenotypes related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
2 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
3 ichthyosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008064
4 jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0000952
5 sparse body hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0002231
6 sparse eyelashes 58 31 hallmark (90%) Very frequent (99-80%) HP:0000653
7 scarring alopecia of scalp 58 31 hallmark (90%) Very frequent (99-80%) HP:0004552
8 sparse scalp hair 31 hallmark (90%) HP:0002209
9 sparse and thin eyebrow 31 hallmark (90%) HP:0000535
10 portal hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0001409
11 abnormality of dental enamel 58 31 occasional (7.5%) Occasional (29-5%) HP:0000682
12 hypodontia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000668
13 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
14 oligodontia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000677
15 dry skin 31 HP:0000958
16 alopecia 31 HP:0001596
17 cholestasis 58 Very frequent (99-80%)
18 thick hair 31 HP:0100874
19 sparse eyebrow 58 Very frequent (99-80%)
20 abnormality of blood and blood-forming tissues 31 HP:0001871
21 hypotrichosis of the scalp 58 Very frequent (99-80%)
22 hypoplasia of dental enamel 31 HP:0006297
23 epidermal acanthosis 31 HP:0025092
24 parakeratosis 31 HP:0001036
25 cholangitis 31 HP:0030151
26 orthokeratosis 31 HP:0040162

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Liver:
hepatomegaly
cholestasis
fibrosis without fatty infiltration or ductular proliferation

Skin Nails Hair Hair:
hypotrichosis
sparse eyelashes
short dystrophic, thick hair
cicatricial frontoparietal alopecia
loss of the outer third of the eyebrows

Hematology:
intracytoplasmic vacuoles in eosinophils, neutrophils and lymphocytes

Skin Nails Hair Skin:
jaundice
parakeratosis
orthokeratosis
acanthosis
papillomatosis
more
Head And Neck Teeth:
hypodontia
oligodontia
enamel hypoplasia

Clinical features from OMIM®:

607626 (Updated 05-Apr-2021)

UMLS symptoms related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:


icterus

Drugs & Therapeutics for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Safety and Efficacy Study of a Single Center, Open-label, Single Arm About the Gene Correction of HBB in Patient-specific iHSCs Using CRISPR/Cas9 That Intervent Subjests With β-thalassemia Mutations Unknown status NCT03728322 Early Phase 1

Search NIH Clinical Center for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis

Genetic Tests for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Genetic tests related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

# Genetic test Affiliating Genes
1 Neonatal Ichthyosis-Sclerosing Cholangitis Syndrome 29 CLDN1

Anatomical Context for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

MalaCards organs/tissues related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

40
Liver

Publications for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Articles related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

# Title Authors PMID Year
1
Confirmation of the origin of NISCH syndrome. 57 6
16619213 2006
2
Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. 57 6
15521008 2004
3
Homozygosity mapping of a locus for a novel syndromic ichthyosis to chromosome 3q27-q28. 57 6
12164927 2002
4
Claudin-1 involved in neonatal ichthyosis sclerosing cholangitis syndrome regulates hepatic paracellular permeability. 61
22030598 2012
5
Molecular basis of intrahepatic cholestasis. 61
15768832 2004

Variations for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

ClinVar genetic disease variations for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLDN16 , CLDN1 NM_021101.5(CLDN1):c.200_201del (p.Val66_Phe67insTer) Deletion Pathogenic 6088 rs864309516 GRCh37: 3:190039795-190039796
GRCh38: 3:190322006-190322007
2 CLDN16 , CLDN1 NM_021101.5(CLDN1):c.358del (p.Val120fs) Deletion Pathogenic 6089 rs864309517 GRCh37: 3:190030691-190030691
GRCh38: 3:190312902-190312902
3 CLDN1 GRCh37/hg19 3q28(chr3:190039387-190040504) copy number loss Pathogenic 625822 GRCh37: 3:190039387-190040504
GRCh38:

Expression for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Search GEO for disease gene expression data for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis.

Pathways for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Pathways related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis according to KEGG:

36
# Name Kegg Source Accession
1 Cell adhesion molecules hsa04514
2 Tight junction hsa04530
3 Leukocyte transendothelial migration hsa04670

Pathways related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.43 CLDN16 CLDN1
2
Show member pathways
12.19 CLDN16 CLDN1
3
Show member pathways
12.02 CLDN16 CLDN1
4
Show member pathways
11.94 CLDN16 CLDN1
5
Show member pathways
11.84 CLDN16 CLDN1
6
Show member pathways
11.71 CLDN16 CLDN1
7 11.18 CLDN16 CLDN1
8 10.8 CLDN16 CLDN1

GO Terms for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

Cellular components related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 8.96 CLDN16 CLDN1
2 bicellular tight junction GO:0005923 8.62 CLDN16 CLDN1

Biological processes related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.16 CLDN16 CLDN1
2 bicellular tight junction assembly GO:0070830 8.96 CLDN16 CLDN1
3 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0016338 8.62 CLDN16 CLDN1

Molecular functions related to Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 8.62 CLDN16 CLDN1

Sources for Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....