MCID: ICH026
MIFTS: 31

Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis

Categories: Genetic diseases, Rare diseases, Liver 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 53 29 13 6 40 73
Nisch Syndrome 57 53 59 75
Neonatal Ichthyosis-Sclerosing Cholangitis Syndrome 57 53 59
Ilvasc 57 53 75
Ichthyosis-Sclerosing Cholangitis Syndrome 57 53
Ichthyosis with Leukocyte Vacuoles, Alopecia and Sclerosing Cholangitis 75
Ichthyosis-Hypotrichosis-Sclerosing Cholangitis Syndrome 59
Neonatal Ichthyosis-Sclerosing Cholangitis Syndrome 37
Ichthyosis-Sclerosing Cholangitis Neonatal Syndrome 75
Nisch 75
Ihsc 59

Characteristics:

Orphanet epidemiological data:

59
neonatal ichthyosis-sclerosing cholangitis syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis:
Inheritance autosomal recessive inheritance


Classifications:



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

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 59303Disease definitionNeonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.EpidemiologyLess than ten patients (from unrelated consanguineous Moroccan families and from Sweden) have been reported so far.Clinical descriptionThe 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.EtiologyNISCH syndrome is caused by a mutation in the CLDN1 gene coding for the tight junction protein claudin-1.Diagnostic methodsDiagnosis is based on clinical, biochemical and histological features.Differential diagnosisThe differential diagnosis should include Dorfman-Chanarin syndrome and other syndromic forms of ichthyosis (see these terms).Genetic counselingNISCH syndrome shows an autosomal recessive pattern of inheritance.Management and treatmentTreatments 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.Visit the Orphanet disease page for more resources.

MalaCards based summary : Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis, also known as nisch syndrome, is related to aplasia of lacrimal and salivary glands and dilated cardiomyopathy, 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 (CAMs) and Tight junction. Affiliated tissues include skin, liver and neutrophil, and related phenotypes are sparse eyelashes and hypodontia

UniProtKB/Swiss-Prot : 75 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.

Description 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:

# Related Disease Score Top Affiliating Genes
1 aplasia of lacrimal and salivary glands 11.1
2 dilated cardiomyopathy 11.1
3 withdrawal disorder 11.1
4 silent myocardial infarction 11.1
5 liver disease 10.2
6 hepatitis 10.0
7 sclerosing cholangitis 10.0
8 ichthyosis 10.0
9 cholangitis 10.0
10 ovarian 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...

Symptoms via clinical synopsis from OMIM:

57
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:
parakeratosis
jaundice
acanthosis
papillomatosis
xerosis
more
Head And Neck Teeth:
hypodontia
oligodontia
enamel hypoplasia


Clinical features from OMIM:

607626

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

59 32 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sparse eyelashes 59 32 hallmark (90%) Very frequent (99-80%) HP:0000653
2 hypodontia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000668
3 oligodontia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000677
4 abnormality of dental enamel 59 32 occasional (7.5%) Occasional (29-5%) HP:0000682
5 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
6 acanthosis nigricans 59 32 occasional (7.5%) Occasional (29-5%) HP:0000956
7 portal hypertension 59 32 occasional (7.5%) Occasional (29-5%) HP:0001409
8 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
9 sparse body hair 59 32 hallmark (90%) Very frequent (99-80%) HP:0002231
10 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
11 scarring alopecia of scalp 59 32 hallmark (90%) Very frequent (99-80%) HP:0004552
12 hypotrichosis of the scalp 59 32 hallmark (90%) Very frequent (99-80%) HP:0004782
13 ichthyosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008064
14 sparse eyebrow 59 Very frequent (99-80%)
15 cholestasis 59 Very frequent (99-80%)
16 dry skin 32 HP:0000958
17 hypotrichosis 32 HP:0001006
18 parakeratosis 32 HP:0001036
19 alopecia 32 HP:0001596
20 abnormality of blood and blood-forming tissues 32 HP:0001871
21 hypoplasia of dental enamel 32 HP:0006297
22 epidermal acanthosis 32 HP:0025092
23 cholangitis 32 HP:0030151
24 orthokeratosis 32 HP:0040162
25 sparse and thin eyebrow 32 hallmark (90%) HP:0000535

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


icterus

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

Search Clinical Trials , 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 Ichthyosis, Leukocyte Vacuoles, Alopecia, and Sclerosing Cholangitis 29 CLDN1

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

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

41
Skin, Liver, Neutrophil

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

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

# Title Authors Year
1
Novel mutation in the CLDN1 gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome. ( 24641442 )
2014
2
Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome). ( 18095941 )
2008
3
Confirmation of the origin of NISCH syndrome. ( 16619213 )
2006

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

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CLDN1 NM_021101.4(CLDN1): c.200_201delTT (p.Phe67Terfs) deletion Pathogenic rs864309516 GRCh37 Chromosome 3, 190039795: 190039796
2 CLDN1 NM_021101.4(CLDN1): c.200_201delTT (p.Phe67Terfs) deletion Pathogenic rs864309516 GRCh38 Chromosome 3, 190322006: 190322007
3 CLDN1 NM_021101.4(CLDN1): c.358delG (p.Val120Serfs) deletion Pathogenic rs864309517 GRCh37 Chromosome 3, 190030691: 190030691
4 CLDN1 NM_021101.4(CLDN1): c.358delG (p.Val120Serfs) deletion Pathogenic rs864309517 GRCh38 Chromosome 3, 190312902: 190312902

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:

37
# Name Kegg Source Accession
1 Cell adhesion molecules (CAMs) hsa04514
2 Tight junction hsa04530
3 Leukocyte transendothelial migration hsa04670

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

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
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34 ICD10 via Orphanet
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45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
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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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