MCID: ICH069
MIFTS: 39

Ichthyosis, Congenital, Autosomal Recessive 4b

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

Aliases & Classifications for Ichthyosis, Congenital, Autosomal Recessive 4b

MalaCards integrated aliases for Ichthyosis, Congenital, Autosomal Recessive 4b:

Name: Ichthyosis, Congenital, Autosomal Recessive 4b 54 71
Harlequin Ichthyosis 12 50 24 25 56 71 52
Harlequin Fetus 50 24 71 69
Autosomal Recessive Congenital Ichthyosis 4b 12 29 14
Ichthyosis Congenita, Harlequin Fetus Type 50 24 25
Hi 25 56 71
Harlequin Type Ichthyosis 72 69
Arci4b 12 71
Ichthyosis Congenita Harlequin Fetus Type 71
Ichthyosis Congenita, Harlequin Type 56
Harlequin Type Ichthyosis Congenita 12
Ichthyosis Fetalis, Harlequin Type 56
Harlequin Type Ichthyosis Fetalis 12
Harlequin Baby Syndrome 25

Characteristics:

Orphanet epidemiological data:

56
harlequin ichthyosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
patients are susceptible to sepsis and dehydration
patients are prone to impaired thermoregulation
usually fatal within the first few weeks of life
surviving infants develop severe nonbullous ichthyosiform erythroderma


HPO:

32
ichthyosis, congenital, autosomal recessive 4b:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare skin diseases


Summaries for Ichthyosis, Congenital, Autosomal Recessive 4b

OMIM : 54
Harlequin ichthyosis is a rare severe form of congenital ichthyosis, which may be fatal. The neonate is encased in an 'armor' of thick scale plates separated by deep fissures. There is bilateral ectropion and eclabium, and the nose and ears are flattened and appear rudimentary. Constricting bands around the extremities can restrict movement and cause digital necrosis. As the skin barrier is severely compromised, neonates are more prone to sepsis, dehydration, and impaired thermoregulation. Treatment with oral retinoids encourages shedding of the grossly thickened skin. Babies who survive into infancy and beyond develop skin changes resembling severe nonbullous congenital ichthyosiform erythroderma (see 242300) (summary by Rajpopat et al., 2011). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass lamellar ichthyosis (LI), nonbullous congenital ichthyosis erythroderma (NCIE), and harlequin ichthyosis (Oji et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). (242500)

MalaCards based summary : Ichthyosis, Congenital, Autosomal Recessive 4b, also known as harlequin ichthyosis, is related to ichthyosis, congenital, autosomal recessive 3 and ectropion, and has symptoms including recurrent respiratory infections, cataract and hyperkeratosis. An important gene associated with Ichthyosis, Congenital, Autosomal Recessive 4b is ABCA12 (ATP Binding Cassette Subfamily A Member 12), and among its related pathways/superpathways is Prostaglandin 2 biosynthesis and metabolism FM. Affiliated tissues include skin and eye.

Disease Ontology : 12 An autosomal recessive congenital ichthyosis characterized by severe neonatal ichthyosis with bilateral ectropion and eclabium, flattened and rudimentary nose and ears, constricting bands around the extremities and frequently lethality during infancy that has material basis in homozygous or compound heterozygous mutation in the ABCA12 gene on chromosome 2q35.

Genetics Home Reference : 25 Harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. Infants with this condition are born with very hard, thick skin covering most of their bodies. The skin forms large, diamond-shaped plates that are separated by deep cracks (fissures). These skin abnormalities affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties and respiratory failure.

NIH Rare Diseases : 50 harlequin ichthyosis is a severe genetic disorder that mainly affects the skin. the newborn infant is covered with plates of thick skin that crack and split apart. the thick plates can pull at and distort facial features and can restrict breathing and eating. mutations in the abca12 gene cause harlequin ichthyosis. this condition is inherited in an autosomal recessive pattern.  last updated: 2/6/2015

UniProtKB/Swiss-Prot : 71 Ichthyosis, congenital, autosomal recessive 4B: A rare, very severe form of congenital ichthyosis, in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period. Babies who survive into infancy and beyond develop skin changes resembling severe non-bullous congenital ichthyosiform erythroderma.

Related Diseases for Ichthyosis, Congenital, Autosomal Recessive 4b

Diseases in the Ichthyosis family:

Ichthyosis, Congenital, Autosomal Recessive 4a Ichthyosis, Congenital, Autosomal Recessive 4b
Ichthyosis, Congenital, Autosomal Recessive 6 Ichthyosis, Congenital, Autosomal Recessive 10
Ichthyosis, Congenital, Autosomal Recessive 8 Ichthyosis, Congenital, Autosomal Recessive 11
Ichthyosis, Congenital, Autosomal Recessive 7 Ichthyosis, Congenital, Autosomal Recessive 13
Ichthyosis, Congenital, Autosomal Recessive 1 Ichthyosis, Congenital, Autosomal Recessive 9
Ichthyosis, Congenital, Autosomal Recessive 2 Ichthyosis, Congenital, Autosomal Recessive 3
Ichthyosis, Congenital, Autosomal Recessive 5 Ichthyosis, Congenital, Autosomal Recessive 12
Ichthyosis, Congenital, Autosomal Recessive 14 Autosomal Recessive Congenital Ichthyosis
Ichthyosis, Acquired Abca12-Related Autosomal Recessive Congenital Ichthyosis
Alox12b-Related Autosomal Recessive Congenital Ichthyosis Aloxe3-Related Autosomal Recessive Congenital Ichthyosis
Cyp4f22-Related Autosomal Recessive Congenital Ichthyosis Lipn-Related Autosomal Recessive Congenital Ichthyosis
Pnpla1-Related Autosomal Recessive Congenital Ichthyosis St14-Related Autosomal Recessive Congenital Ichthyosis
Tgm1-Related Autosomal Recessive Congenital Ichthyosis

Diseases related to Ichthyosis, Congenital, Autosomal Recessive 4b via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
id Related Disease Score Top Affiliating Genes
1 ichthyosis, congenital, autosomal recessive 3 29.0 ALOX12B ALOXE3 NIPAL4 TGM1
2 ectropion 11.0
3 isotretinoin syndrome 11.0
4 ichthyosis histrix, curth-macklin type 10.9
5 ichthyosis hystrix gravior 10.9
6 ichthyosis, congenital, autosomal recessive 4a 10.7
7 ichthyosis, congenital, autosomal recessive 6 10.7
8 ichthyosis, congenital, autosomal recessive 10 10.7
9 ichthyosis, congenital, autosomal recessive 8 10.7
10 ichthyosis, congenital, autosomal recessive 11 10.7
11 ichthyosis, congenital, autosomal recessive 7 10.7
12 ichthyosis, congenital, autosomal recessive 1 10.7
13 ichthyosis, congenital, autosomal recessive 9 10.7
14 ichthyosis, congenital, autosomal recessive 2 10.7
15 ichthyosis, congenital, autosomal recessive 5 10.7
16 ichthyosis, congenital, autosomal recessive 12 10.7
17 communicating hydrocephalus 10.1 ABCA12 TGM1
18 cervical clear cell adenocarcinoma 10.1 ABCA12 TGM1
19 chondrodysplasia punctata, x-linked recessive 9.9 FLG TGM1
20 ichthyosis vulgaris 9.8 ABCA12 FLG TGM1
21 small non-cleaved cell lymphoma 9.7 ABCA12 FLG TGM1
22 ichthyosis 9.7
23 renal dysplasia 9.7
24 polydactyly 9.7
25 diastrophic dysplasia 9.7 FLG TGM1
26 deafness, autosomal dominant 53 7.8 ABCA12 ALOX12B ALOXE3 CYP4F22 NIPAL4 TGM1
27 amyotrophic lateral sclerosis 19 7.4 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4
28 catecholaminergic polymorphic ventricular tachycardia 5 7.4 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4
29 richter's syndrome 7.3 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4
30 steroid inherited metabolic disorder 7.3 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4

Graphical network of the top 20 diseases related to Ichthyosis, Congenital, Autosomal Recessive 4b:



Diseases related to Ichthyosis, Congenital, Autosomal Recessive 4b

Symptoms & Phenotypes for Ichthyosis, Congenital, Autosomal Recessive 4b

Symptoms via clinical synopsis from OMIM:

54

Prenatal Manifestations- Delivery:
premature birth

Head And Neck- Nose:
flattened
rudimentary

Head And Neck- Eyes:
severe ectropion
bulging eyes

Skeletal- Limbs:
constricting bands around extremities at birth
semiflexed rigid limbs

Skeletal- Feet:
necrotic distal toes

Laboratory- Abnormalities:
tonofibril defect (cross-beta-protein structure)

Skin Nails & Hair- Skin:
collodion membrane at birth
harlequin fetus
large diamond-shaped plaques

Head And Neck- Ears:
flattened
rudimentary

Head And Neck- Mouth:
eclabium

Skeletal- Hands:
hypoplastic fingers
necrotic fingertips

Skin Nails & Hair- Skin Histology:
abnormal lamellar granule formation


Clinical features from OMIM:

242500

Human phenotypes related to Ichthyosis, Congenital, Autosomal Recessive 4b:

56 32 (show all 23)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 recurrent respiratory infections 56 32 hallmark (90%) Very frequent (99-80%) HP:0002205
2 cataract 56 32 occasional (7.5%) Occasional (29-5%) HP:0000518
3 hyperkeratosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000962
4 sudden cardiac death 56 32 occasional (7.5%) Occasional (29-5%) HP:0001645
5 respiratory insufficiency 56 32 occasional (7.5%) Occasional (29-5%) HP:0002093
6 self-injurious behavior 56 32 occasional (7.5%) Occasional (29-5%) HP:0100716
7 dehydration 56 32 occasional (7.5%) Occasional (29-5%) HP:0001944
8 malignant hyperthermia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002047
9 ectropion 56 32 hallmark (90%) Very frequent (99-80%) HP:0000656
10 depressed nasal ridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0000457
11 erythroderma 56 32 frequent (33%) Frequent (79-30%) HP:0001019
12 congenital ichthyosiform erythroderma 56 32 hallmark (90%) Very frequent (99-80%) HP:0007431
13 eclabion 56 32 frequent (33%) Frequent (79-30%) HP:0012472
14 limitation of joint mobility 56 32 frequent (33%) Frequent (79-30%) HP:0001376
15 hearing abnormality 56 32 hallmark (90%) Very frequent (99-80%) HP:0000364
16 hand polydactyly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001161
17 foot polydactyly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001829
18 proptosis 32 HP:0000520
19 premature birth 32 HP:0001622
20 rigidity 32 HP:0002063
21 ichthyosis 56 Very frequent (99-80%)
22 everted lower lip vermilion 32 HP:0000232
23 short finger 32 HP:0009381

Drugs & Therapeutics for Ichthyosis, Congenital, Autosomal Recessive 4b

Search Clinical Trials , NIH Clinical Center for Ichthyosis, Congenital, Autosomal Recessive 4b

Genetic Tests for Ichthyosis, Congenital, Autosomal Recessive 4b

Genetic tests related to Ichthyosis, Congenital, Autosomal Recessive 4b:

id Genetic test Affiliating Genes
1 Autosomal Recessive Congenital Ichthyosis 4b 29
2 Harlequin Ichthyosis 24 ABCA12

Anatomical Context for Ichthyosis, Congenital, Autosomal Recessive 4b

MalaCards organs/tissues related to Ichthyosis, Congenital, Autosomal Recessive 4b:

39
Skin, Eye

Publications for Ichthyosis, Congenital, Autosomal Recessive 4b

Variations for Ichthyosis, Congenital, Autosomal Recessive 4b

UniProtKB/Swiss-Prot genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 4b:

71
id Symbol AA change Variation ID SNP ID
1 ABCA12 p.Ser387Asn VAR_067076 rs746315995
2 ABCA12 p.Gly1179Arg VAR_067078 rs267606622

ClinVar genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 4b:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ABCA12 NM_173076.2(ABCA12): c.7323delC (p.Val2442Serfs) deletion Pathogenic rs387906284 GRCh37 Chromosome 2, 215809745: 215809745
2 ABCA12 NM_173076.2(ABCA12): c.5012delA (p.Asn1671Ilefs) deletion Pathogenic rs387906285 GRCh37 Chromosome 2, 215843156: 215843156
3 ABCA12 NM_173076.2(ABCA12): c.6610C> T (p.Arg2204Ter) single nucleotide variant Pathogenic rs137853289 GRCh37 Chromosome 2, 215818615: 215818615
4 ABCA12 NM_173076.2(ABCA12): c.3535G> A (p.Gly1179Arg) single nucleotide variant Pathogenic rs267606622 GRCh37 Chromosome 2, 215855515: 215855515
5 ABCA12 NM_173076.2(ABCA12): c.986-?_1061+?del (p.Asp330_Gln354delinsSerfs) deletion Pathogenic GRCh37 Chromosome 2, 215891663: 215901676
6 ABCA12 ABCA12, ARG287TER single nucleotide variant Pathogenic
7 ABCA12 NM_173076.2(ABCA12): c.5939+4A> G single nucleotide variant Likely pathogenic rs1131692156 GRCh38 Chromosome 2, 214959020: 214959020

Expression for Ichthyosis, Congenital, Autosomal Recessive 4b

Search GEO for disease gene expression data for Ichthyosis, Congenital, Autosomal Recessive 4b.

Pathways for Ichthyosis, Congenital, Autosomal Recessive 4b

Pathways related to Ichthyosis, Congenital, Autosomal Recessive 4b according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 9.98 ALOX12B ALOXE3

GO Terms for Ichthyosis, Congenital, Autosomal Recessive 4b

Cellular components related to Ichthyosis, Congenital, Autosomal Recessive 4b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cornified envelope GO:0001533 8.62 FLG TGM1

Biological processes related to Ichthyosis, Congenital, Autosomal Recessive 4b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cornification GO:0070268 9.48 FLG TGM1
2 peptide cross-linking GO:0018149 9.46 FLG TGM1
3 sphingolipid metabolic process GO:0006665 9.43 ALOX12B ALOXE3
4 ceramide biosynthetic process GO:0046513 9.4 ALOX12B ALOXE3
5 arachidonic acid metabolic process GO:0019369 9.37 ALOX12B ALOXE3
6 keratinocyte differentiation GO:0030216 9.33 ABCA12 FLG TGM1
7 linoleic acid metabolic process GO:0043651 9.32 ALOX12B ALOXE3
8 lipoxygenase pathway GO:0019372 9.26 ALOX12B ALOXE3
9 hepoxilin biosynthetic process GO:0051122 8.96 ALOX12B ALOXE3
10 establishment of skin barrier GO:0061436 8.92 ABCA12 ALOX12B ALOXE3 FLG

Molecular functions related to Ichthyosis, Congenital, Autosomal Recessive 4b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.43 ALOX12B ALOXE3 CYP4F22
2 dioxygenase activity GO:0051213 9.16 ALOX12B ALOXE3
3 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen GO:0016702 8.96 ALOX12B ALOXE3
4 iron ion binding GO:0005506 8.8 ALOX12B ALOXE3 CYP4F22

Sources for Ichthyosis, Congenital, Autosomal Recessive 4b

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10 dbSNP
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16 ExPASy
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70 UMLS via Orphanet
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