MCID: ICH069
MIFTS: 44

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 53 71
Harlequin Ichthyosis 53 12 49 24 55 71 36 51
Hi 53 24 55 71
Autosomal Recessive Congenital Ichthyosis 4b 12 28 14
Ichthyosis Congenita, Harlequin Fetus Type 53 49 24
Harlequin Fetus 49 71 69
Arci4b 53 12 71
Harlequin Type Ichthyosis 72 69
Ichthyosis Congenita Harlequin Fetus Type 71
Ichthyosis Congenita, Harlequin Type 55
Harlequin Type Ichthyosis Congenita 12
Ichthyosis Fetalis, Harlequin Type 55
Harlequin Type Ichthyosis Fetalis 12
Harlequin Ichthyosis; Hi 53
Harlequin Baby Syndrome 24
'harlequin Fetus' 53

Characteristics:

Orphanet epidemiological data:

55
harlequin ichthyosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
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:

31
ichthyosis, congenital, autosomal recessive 4b:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare skin diseases


Summaries for Ichthyosis, Congenital, Autosomal Recessive 4b

OMIM : 53 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 ectropion and ichthyosis, congenital, autosomal recessive 4a, and has symptoms including sudden cardiac death, respiratory insufficiency and self-injurious behavior. 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 are ABC transporters and 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 : 24 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 : 49 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 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 4b via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 ectropion 31.7 ABCA12 TGM1
2 ichthyosis, congenital, autosomal recessive 4a 31.4 ABCA12 TGM1
3 ichthyosis, congenital, autosomal recessive 2 29.7 ALOX12B ALOXE3 NIPAL4 TGM1
4 ichthyosis, congenital, autosomal recessive 1 28.2 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4
5 ichthyosis 27.2 ABCA12 ALOX12B ALOXE3 CYP4F22 FLG NIPAL4
6 isotretinoin syndrome 11.1
7 ichthyosis hystrix, curth-macklin type 11.0
8 ichthyosis hystrix gravior 11.0
9 ichthyosis, congenital, autosomal recessive 11 10.8
10 ichthyosis, congenital, autosomal recessive 5 10.8
11 ichthyosis, congenital, autosomal recessive 3 10.8
12 ichthyosis, congenital, autosomal recessive 6 10.8
13 ichthyosis, congenital, autosomal recessive 8 10.8
14 ichthyosis, congenital, autosomal recessive 7 10.8
15 ichthyosis, congenital, autosomal recessive 9 10.8
16 ichthyosis, congenital, autosomal recessive 10 10.8
17 ichthyosis, congenital, autosomal recessive 12 10.8
18 eyelid disease 10.0 ABCA12 TGM1
19 ichthyosis, x-linked 9.9 FLG TGM1
20 polydactyly 9.8
21 ichthyosis vulgaris 9.8 ABCA12 FLG TGM1
22 skin disease 9.7 ABCA12 FLG TGM1
23 netherton syndrome 9.7 FLG TGM1
24 self-improving collodion baby 9.4 ALOX12B ALOXE3 TGM1
25 autosomal recessive congenital ichthyosis 8.3 ABCA12 ALOX12B ALOXE3 CYP4F22 NIPAL4 TGM1
26 congenital ichthyosiform erythroderma 8.0 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:

53
Prenatal Manifestations Delivery:
premature birth

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

Head And Neck Ears:
flattened
rudimentary

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

Skeletal Feet:
necrotic distal toes

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

Head And Neck Eyes:
bulging eyes
severe ectropion

Head And Neck Mouth:
eclabium

Head And Neck Nose:
flattened
rudimentary

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:

55 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sudden cardiac death 55 31 occasional (7.5%) Occasional (29-5%) HP:0001645
2 respiratory insufficiency 55 31 occasional (7.5%) Occasional (29-5%) HP:0002093
3 self-injurious behavior 55 31 occasional (7.5%) Occasional (29-5%) HP:0100716
4 cataract 55 31 occasional (7.5%) Occasional (29-5%) HP:0000518
5 recurrent respiratory infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0002205
6 dehydration 55 31 occasional (7.5%) Occasional (29-5%) HP:0001944
7 hyperkeratosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000962
8 limitation of joint mobility 55 31 frequent (33%) Frequent (79-30%) HP:0001376
9 hearing abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0000364
10 depressed nasal ridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0000457
11 hand polydactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001161
12 foot polydactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001829
13 malignant hyperthermia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002047
14 ectropion 55 31 hallmark (90%) Very frequent (99-80%) HP:0000656
15 erythroderma 55 31 frequent (33%) Frequent (79-30%) HP:0001019
16 congenital ichthyosiform erythroderma 55 31 hallmark (90%) Very frequent (99-80%) HP:0007431
17 eclabion 55 31 frequent (33%) Frequent (79-30%) HP:0012472
18 ichthyosis 55 Very frequent (99-80%)
19 everted lower lip vermilion 31 HP:0000232
20 rigidity 31 HP:0002063
21 proptosis 31 HP:0000520
22 short finger 31 HP:0009381
23 premature birth 31 HP:0001622

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 National Registry for Ichthyosis and Related Disorders Unknown status NCT00074685 Not Applicable

Search 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:

# Genetic test Affiliating Genes
1 Autosomal Recessive Congenital Ichthyosis 4b 28 ABCA12

Anatomical Context for Ichthyosis, Congenital, Autosomal Recessive 4b

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

38
Skin, Eye

Publications for Ichthyosis, Congenital, Autosomal Recessive 4b

Articles related to Ichthyosis, Congenital, Autosomal Recessive 4b:

(show all 38)
# Title Authors Year
1
Compound heterozygous mutations with novel missense<i>ABCA12</i>mutation in harlequin ichthyosis. ( 29298786 )
2018
2
Harlequin ichthyosis due to novel splice site mutation in the ABCA12 gene: postnatal to prenatal diagnosis. ( 29377090 )
2018
3
Harlequin Ichthyosis - A Case Report. ( 29341518 )
2017
4
Harlequin ichthyosis: A rare case. ( 28913151 )
2017
5
Noteworthy clinical findings of harlequin ichthyosis: Digital autoamputation caused by cutaneous constriction bands in a case with novel ABCA12 mutations. ( 26473995 )
2015
6
Novel ABCA12 mutations in harlequin ichthyosis: a journey from photo diagnosis to prenatal diagnosis. ( 25479012 )
2015
7
A novel mutation in the ABCA12 gene in a Turkish case of Harlequin ichthyosis. ( 25563821 )
2015
8
Techniques for toddlers: linear band incision for harlequin ichthyosis with associated compartment syndrome. ( 25187390 )
2014
9
Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis. ( 25209981 )
2014
10
Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. ( 21339420 )
2011
11
Harlequin ichthyosis in two siblings. ( 21798141 )
2011
12
[Harlequin ichthyosis--medical and psychosocial challenges]. ( 20166009 )
2010
13
Premature terminal differentiation and a reduction in specific proteases associated with loss of ABCA12 in Harlequin ichthyosis. ( 19179616 )
2009
14
Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis. ( 19664001 )
2009
15
Harlequin ichthyosis model mouse reveals alveolar collapse and severe fetal skin barrier defects. ( 18632686 )
2008
16
Novel and recurring ABCA12 mutations associated with harlequin ichthyosis: implications for prenatal diagnosis. ( 17986308 )
2008
17
Prenatal diagnosis of Harlequin ichthyosis presenting as distal arthrogryposis using three-dimensional ultrasound. ( 17385787 )
2007
18
Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity. ( 16675967 )
2006
19
ABCA12 is the major harlequin ichthyosis gene. ( 16902423 )
2006
20
Harlequin ichthyosis and other autosomal recessive congenital ichthyoses: the underlying genetic defects and pathomechanisms. ( 16481150 )
2006
21
Pathomechanisms of harlequin ichthyosis and ABCA transporters in human diseases. ( 16847209 )
2006
22
Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. ( 15756637 )
2005
23
Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. ( 16007253 )
2005
24
Harlequin ichthyosis unmasked: a defect of lipid transport. ( 16007249 )
2005
25
Epidermal-specific defect of GPI anchor in Pig-a null mice results in Harlequin ichthyosis-like features. ( 15304084 )
2004
26
Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis. ( 14521561 )
2003
27
The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis. ( 12839564 )
2003
28
The ichq mutant mouse, a model for the human skin disorder harlequin ichthyosis: mapping, keratinocyte culture, and consideration of candidate genes involved in epidermal growth regulation. ( 12823437 )
2003
29
Repair of cicatricial ectropion in an infant with harlequin ichthyosis using engineered human skin. ( 12208260 )
2002
30
Ultrastructural features resembling those of harlequin ichthyosis in patients with severe congenital ichthyosiform erythroderma. ( 11531841 )
2001
31
Transglutaminase 1 expression in a patient with features of harlequin ichthyosis: case report. ( 9486708 )
1998
32
Expression of transglutaminase 1 (transglutaminase K) in harlequin ichthyosis. ( 9049047 )
1997
33
Harlequin ichthyosis keratinocytes in lifted culture differentiate poorly by morphologic and biochemical criteria. ( 9204952 )
1997
34
Protein phosphatase activity in human keratinocytes cultured from normal epidermis and epidermis from patients with harlequin ichthyosis. ( 9470902 )
1997
35
Cornified cell envelope proteins and keratins are normally distributed in harlequin ichthyosis. ( 9001990 )
1996
36
Harlequin ichthyosis. Variability in expression and hypothesis for disease mechanism. ( 7694551 )
1993
37
Heterogeneity in harlequin ichthyosis, an inborn error of epidermal keratinization: variable morphology and structural protein expression and a defect in lamellar granules. ( 1688598 )
1990
38
Congenital ichthyosiform erythroderma and harlequin ichthyosis. ( 6680117 )
1983

Variations for Ichthyosis, Congenital, Autosomal Recessive 4b

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

71
# 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
# 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 NM_173076.2(ABCA12): c.859C> T (p.Arg287Ter) single nucleotide variant Pathogenic rs11891778 GRCh37 Chromosome 2, 215910574: 215910574
7 ABCA12 NM_173076.2(ABCA12): c.5939+4A> G single nucleotide variant Likely pathogenic rs1131692156 GRCh38 Chromosome 2, 214959020: 214959020
8 ABCA12 NM_173076.2(ABCA12): c.6234-1G> C single nucleotide variant Likely pathogenic GRCh37 Chromosome 2, 215820086: 215820086

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 KEGG:

36
# Name Kegg Source Accession
1 ABC transporters hsa02010

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

# 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:

# 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:

# 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:

# 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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