ARCL1B
MCID: CTS037
MIFTS: 39

Cutis Laxa, Autosomal Recessive, Type Ib (ARCL1B)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Cutis Laxa, Autosomal Recessive, Type Ib

MalaCards integrated aliases for Cutis Laxa, Autosomal Recessive, Type Ib:

Name: Cutis Laxa, Autosomal Recessive, Type Ib 57 13 72
Arcl1b 57 12 74
Autosomal Recessive Cutis Laxa Type Ib 12 15
Lethal Arteriopathy Syndrome Due to Fibulin-4 Deficiency 59
Cutis Laxa, Autosomal Recessive, Type 1b 40
Cutis Laxa Autosomal Recessive Type Ib 74
Cutis Laxa, Autosomal Recessive, 1b 74

Characteristics:

Orphanet epidemiological data:

59
lethal arteriopathy syndrome due to fibulin-4 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
relatively mild cutis laxa, associated with severe vascular abnormalities
massive aortic aneurysm can cause airway compression in affected infants


HPO:

32
cutis laxa, autosomal recessive, type ib:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070133
MeSH 44 D003483
ICD10 33 Q82.8
Orphanet 59 ORPHA314718
UMLS 72 C3280798

Summaries for Cutis Laxa, Autosomal Recessive, Type Ib

UniProtKB/Swiss-Prot : 74 Cutis laxa, autosomal recessive, 1B: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.

MalaCards based summary : Cutis Laxa, Autosomal Recessive, Type Ib, also known as arcl1b, is related to cutis laxa and efemp2-related cutis laxa. An important gene associated with Cutis Laxa, Autosomal Recessive, Type Ib is EFEMP2 (EGF Containing Fibulin Extracellular Matrix Protein 2), and among its related pathways/superpathways are Collagen chain trimerization and Degradation of the extracellular matrix. Affiliated tissues include skin, brain and eye, and related phenotypes are depressed nasal bridge and microcephaly

Disease Ontology : 12 An autosomal recessive cutis laxa type I characterized by disturbed elastic fiber formation resulting in severe systemic connective tissue abnormalities that has material basis in homozygous or compound heterozygous mutation in the EFEMP2 gene on chromosome 11q13.

OMIM : 57 Autosomal recessive cutis laxa type IB (ARCL1B) is characterized by the presence of severe systemic connective tissue abnormalities, including emphysema, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels. All symptoms refer to disturbed elastic fiber formation (summary by Hoyer et al., 2009). For a complete phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (614437)

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Ib

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Recessive, Type Ib:



Diseases related to Cutis Laxa, Autosomal Recessive, Type Ib

Symptoms & Phenotypes for Cutis Laxa, Autosomal Recessive, Type Ib

Human phenotypes related to Cutis Laxa, Autosomal Recessive, Type Ib:

32 (show all 30)
# Description HPO Frequency HPO Source Accession
1 depressed nasal bridge 32 occasional (7.5%) HP:0005280
2 microcephaly 32 occasional (7.5%) HP:0000252
3 convex nasal ridge 32 occasional (7.5%) HP:0000444
4 oligohydramnios 32 occasional (7.5%) HP:0001562
5 overgrowth 32 occasional (7.5%) HP:0001548
6 bradycardia 32 occasional (7.5%) HP:0001662
7 hypertelorism 32 HP:0000316
8 low-set ears 32 HP:0000369
9 pectus excavatum 32 HP:0000767
10 high palate 32 HP:0000218
11 inguinal hernia 32 HP:0000023
12 prominent forehead 32 HP:0011220
13 emphysema 32 HP:0002097
14 micrognathia 32 HP:0000347
15 generalized hypotonia 32 HP:0001290
16 abnormality of the pinna 32 HP:0000377
17 arachnodactyly 32 HP:0001166
18 joint hypermobility 32 HP:0001382
19 downslanted palpebral fissures 32 HP:0000494
20 bulbous nose 32 HP:0000414
21 proptosis 32 HP:0000520
22 congenital diaphragmatic hernia 32 HP:0000776
23 aortic aneurysm 32 HP:0004942
24 narrow palpebral fissure 32 HP:0045025
25 cutis laxa 32 HP:0000973
26 soft skin 32 HP:0000977
27 pulmonary insufficiency 32 HP:0010444
28 pulmonary artery aneurysm 32 HP:0004937
29 prominence of the premaxilla 32 HP:0010759
30 generalized arterial tortuosity 32 HP:0004955

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
dysplastic ears

Genitourinary External Genitalia Male:
inguinal hernia

Respiratory Lung:
emphysema

Skeletal Feet:
arachnodactyly

Skin Nails Hair Skin:
cutis laxa
velvety skin
normal scarring

Head And Neck Eyes:
downslanting palpebral fissures
prominent eyes
small palpebral fissures
hypertelorism, mild

Head And Neck Nose:
bulbous nasal tip (in some patients)
depressed nasal bridge (in some patients)
hooked nose (in some patients)

Chest Diaphragm:
diaphragmatic hernia
hypoplastic diaphragm

Growth Other:
fetal overgrowth (in some patients)

Skin Nails Hair Skin Histology:
vascularization increased in upper dermis
collagen bundles smaller than normal
underdeveloped elastic fibers, severe

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Head And Neck Face:
prominent forehead
micrognathia
prominent premaxilla

Skeletal Hands:
arachnodactyly
contractures of third to fifth fingers

Cardiovascular Vascular:
aortic aneurysm
pulmonary artery aneurysm
arterial aneurysms, multiple
arterial tortuosity, general
venous tortuosity
more
Neurologic Central Nervous System:
hypotonia
brain hemorrhage

Head And Neck Mouth:
high-arched palate

Head And Neck Head:
microcephaly (rare)

Skeletal:
fractures at birth
joint hypermobility, generalized

Cardiovascular Heart:
thickened myocardium (rare)
bradycardia (rare)

Prenatal Manifestations Amniotic Fluid:
oligohydramnios (in some patients)

Clinical features from OMIM:

614437

Drugs & Therapeutics for Cutis Laxa, Autosomal Recessive, Type Ib

Search Clinical Trials , NIH Clinical Center for Cutis Laxa, Autosomal Recessive, Type Ib

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Ib

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Ib

MalaCards organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Ib:

41
Skin, Brain, Eye

Publications for Cutis Laxa, Autosomal Recessive, Type Ib

Articles related to Cutis Laxa, Autosomal Recessive, Type Ib:

(show all 12)
# Title Authors PMID Year
1
Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis. 8 71
22943132 2012
2
Altered TGFbeta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency. 8 71
20389311 2010
3
Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation. 8 71
19664000 2009
4
Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa. 8 71
17937443 2007
5
Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. 8 71
16685658 2006
6
Long tortuous aorta in a child with Larsen syndrome. 8 71
15776121 2005
7
Clinicopathologic findings in congenital aneurysms of the great vessels. 8 71
8985490 1996
8
EFEMP2-Related Cutis Laxa 38 71
21563328 2011
9
Keratoglobus with ARCL1B (EFEMP2 gene) cutis laxa. 38
31194159 2019
10
Severe Phenotype of Cutis Laxa Type 1B with Antenatal Signs due to a Novel Homozygous Nonsense Mutation in EFEMP2. 38
30140196 2018
11
Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries. 38
28508064 2017
12
Longer term survival of a child with autosomal recessive cutis laxa due to a mutation in FBLN4. 38
23532871 2013

Variations for Cutis Laxa, Autosomal Recessive, Type Ib

ClinVar genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Ib:

6 (show top 50) (show all 83)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 EFEMP2 NM_016938.5(EFEMP2): c.169G> A (p.Glu57Lys) single nucleotide variant Pathogenic rs119489101 11:65638826-65638826 11:65871355-65871355
2 EFEMP2 NM_016938.5(EFEMP2): c.835C> T (p.Arg279Cys) single nucleotide variant Pathogenic rs119489102 11:65635993-65635993 11:65868522-65868522
3 EFEMP2 NM_016938.5(EFEMP2): c.1070_1073dup (p.Asp359fs) duplication Pathogenic rs193302865 11:65635429-65635432 11:65867958-65867961
4 EFEMP2 NM_016938.5(EFEMP2): c.679C> T (p.Arg227Cys) single nucleotide variant Pathogenic rs397514683 11:65637376-65637376 11:65869905-65869905
5 EFEMP2 NM_016938.5(EFEMP2): c.800G> A (p.Cys267Tyr) single nucleotide variant Pathogenic rs193302866 11:65636028-65636028 11:65868557-65868557
6 EFEMP2 NM_016938.5(EFEMP2): c.608A> C (p.Asp203Ala) single nucleotide variant Pathogenic rs193302864 11:65637447-65637447 11:65869976-65869976
7 EFEMP2 NM_016938.5(EFEMP2): c.577del (p.Gln193fs) deletion Pathogenic rs193302870 11:65637622-65637622 11:65870151-65870151
8 EFEMP2 NM_016938.5(EFEMP2): c.377A> T (p.Glu126Val) single nucleotide variant Pathogenic rs193302869 11:65638120-65638120 11:65870649-65870649
9 EFEMP2 NM_016938.5(EFEMP2): c.376G> A (p.Glu126Lys) single nucleotide variant Pathogenic rs193302867 11:65638121-65638121 11:65870650-65870650
10 EFEMP2 NM_016938.5(EFEMP2): c.1189G> A (p.Ala397Thr) single nucleotide variant Pathogenic rs193302868 11:65634532-65634532 11:65867061-65867061
11 EFEMP2 NM_016938.5(EFEMP2): c.1110dup (p.Gly371fs) duplication Likely pathogenic rs1555042727 11:65635392-65635392 11:65867921-65867921
12 EFEMP2 NM_016938.5(EFEMP2): c.608-1G> C single nucleotide variant Likely pathogenic 11:65637448-65637448 11:65869977-65869977
13 EFEMP2 NM_016938.5(EFEMP2): c.1188C> T (p.Ser396=) single nucleotide variant Conflicting interpretations of pathogenicity rs2234473 11:65634533-65634533 11:65867062-65867062
14 EFEMP2 NM_016938.5(EFEMP2): c.934A> G (p.Thr312Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs148410446 11:65635806-65635806 11:65868335-65868335
15 EFEMP2 NM_016938.5(EFEMP2): c.885C> T (p.Ser295=) single nucleotide variant Conflicting interpretations of pathogenicity rs142509316 11:65635855-65635855 11:65868384-65868384
16 EFEMP2 NM_016938.5(EFEMP2): c.161-10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs2234461 11:65638844-65638844 11:65871373-65871373
17 EFEMP2 NM_016938.5(EFEMP2): c.139C> T (p.Pro47Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs144320036 11:65639462-65639462 11:65871991-65871991
18 EFEMP2 NM_016938.5(EFEMP2): c.277G> A (p.Gly93Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs2234462 11:65638718-65638718 11:65871247-65871247
19 EFEMP2 NM_016938.5(EFEMP2): c.728-3C> T single nucleotide variant Conflicting interpretations of pathogenicity rs377139656 11:65636103-65636103 11:65868632-65868632
20 EFEMP2 NM_016938.5(EFEMP2): c.1207C> A (p.Arg403=) single nucleotide variant Uncertain significance rs765684268 11:65634514-65634514 11:65867043-65867043
21 EFEMP2 NM_016938.5(EFEMP2): c.346G> A (p.Asp116Asn) single nucleotide variant Uncertain significance rs370759216 11:65638649-65638649 11:65871178-65871178
22 EFEMP2 NM_016938.5(EFEMP2): c.253G> A (p.Ala85Thr) single nucleotide variant Uncertain significance rs148604051 11:65638742-65638742 11:65871271-65871271
23 EFEMP2 NM_016938.5(EFEMP2): c.595C> T (p.Arg199Cys) single nucleotide variant Uncertain significance rs766531680 11:65637604-65637604 11:65870133-65870133
24 EFEMP2 NM_016938.5(EFEMP2): c.1105T> C (p.Tyr369His) single nucleotide variant Uncertain significance rs373485109 11:65635397-65635397 11:65867926-65867926
25 EFEMP2 NM_016938.5(EFEMP2): c.1016A> T (p.Gln339Leu) single nucleotide variant Uncertain significance rs754118526 11:65635486-65635486 11:65868015-65868015
26 EFEMP2 NM_016938.5(EFEMP2): c.307G> A (p.Ala103Thr) single nucleotide variant Uncertain significance rs1008465800 11:65638688-65638688 11:65871217-65871217
27 EFEMP2 NM_016938.5(EFEMP2): c.290C> T (p.Pro97Leu) single nucleotide variant Uncertain significance rs779247685 11:65638705-65638705 11:65871234-65871234
28 EFEMP2 NM_016938.5(EFEMP2): c.279C> T (p.Gly93=) single nucleotide variant Uncertain significance rs769750626 11:65638716-65638716 11:65871245-65871245
29 EFEMP2 NM_016938.5(EFEMP2): c.1234G> C (p.Val412Leu) single nucleotide variant Uncertain significance 11:65634487-65634487 11:65867016-65867016
30 EFEMP2 NM_016938.5(EFEMP2): c.579G> C (p.Gln193His) single nucleotide variant Uncertain significance 11:65637620-65637620 11:65870149-65870149
31 EFEMP2 NM_016938.5(EFEMP2): c.1211C> T (p.Pro404Leu) single nucleotide variant Uncertain significance 11:65634510-65634510 11:65867039-65867039
32 EFEMP2 NM_016938.5(EFEMP2): c.977G> A (p.Arg326His) single nucleotide variant Uncertain significance rs141868759 11:65635525-65635525 11:65868054-65868054
33 EFEMP2 NM_016938.5(EFEMP2): c.862G> C (p.Glu288Gln) single nucleotide variant Uncertain significance rs752273286 11:65635878-65635878 11:65868407-65868407
34 EFEMP2 NM_016938.5(EFEMP2): c.338A> G (p.Tyr113Cys) single nucleotide variant Uncertain significance rs1394549414 11:65638657-65638657 11:65871186-65871186
35 EFEMP2 NM_016938.5(EFEMP2): c.1111G> A (p.Gly371Ser) single nucleotide variant Uncertain significance rs1294797610 11:65635391-65635391 11:65867920-65867920
36 EFEMP2 NM_016938.5(EFEMP2): c.1212G> A (p.Pro404=) single nucleotide variant Uncertain significance rs148302546 11:65634509-65634509 11:65867038-65867038
37 EFEMP2 NM_016938.5(EFEMP2): c.1234G> T (p.Val412Leu) single nucleotide variant Uncertain significance 11:65634487-65634487 11:65867016-65867016
38 EFEMP2 NM_016938.5(EFEMP2): c.1283C> T (p.Ala428Val) single nucleotide variant Uncertain significance 11:65634438-65634438 11:65866967-65866967
39 EFEMP2 NM_016938.5(EFEMP2): c.348C> A (p.Asp116Glu) single nucleotide variant Uncertain significance 11:65638647-65638647 11:65871176-65871176
40 covers 29 genes, none of which curated to show dosage sensitivity NC_000011.9: g.(?_65633902)_(66115026_?)dup duplication Uncertain significance 11:65633902-66115026 11:65866431-66347555
41 EFEMP2 NM_016938.5(EFEMP2): c.236T> G (p.Leu79Trp) single nucleotide variant Uncertain significance 11:65638759-65638759 11:65871288-65871288
42 EFEMP2 NM_016938.5(EFEMP2): c.259G> A (p.Val87Ile) single nucleotide variant Uncertain significance 11:65638736-65638736 11:65871265-65871265
43 EFEMP2 NM_016938.5(EFEMP2): c.280G> A (p.Glu94Lys) single nucleotide variant Uncertain significance 11:65638715-65638715 11:65871244-65871244
44 EFEMP2 NM_016938.5(EFEMP2): c.349G> A (p.Asp117Asn) single nucleotide variant Uncertain significance 11:65638646-65638646 11:65871175-65871175
45 EFEMP2 NM_016938.5(EFEMP2): c.554G> A (p.Arg185His) single nucleotide variant Uncertain significance 11:65637645-65637645 11:65870174-65870174
46 EFEMP2 NM_016938.5(EFEMP2): c.946G> T (p.Val316Leu) single nucleotide variant Uncertain significance 11:65635794-65635794 11:65868323-65868323
47 EFEMP2 NM_016938.5(EFEMP2): c.1065C> A (p.Ser355Arg) single nucleotide variant Uncertain significance 11:65635437-65635437 11:65867966-65867966
48 EFEMP2 NM_016938.5(EFEMP2): c.1174del (p.Ile392fs) deletion Uncertain significance 11:65634547-65634547 11:65867078-65867078
49 EFEMP2 NM_016938.5(EFEMP2): c.167A> G (p.Asn56Ser) single nucleotide variant Uncertain significance 11:65638828-65638828 11:65871357-65871357
50 EFEMP2 NM_016938.5(EFEMP2): c.1183G> A (p.Val395Ile) single nucleotide variant Uncertain significance rs543567156 11:65634538-65634538 11:65867067-65867067

UniProtKB/Swiss-Prot genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Ib:

74
# Symbol AA change Variation ID SNP ID
1 EFEMP2 p.Glu57Lys VAR_027019 rs119489101
2 EFEMP2 p.Cys267Tyr VAR_067069 rs193302866
3 EFEMP2 p.Arg279Cys VAR_067070 rs119489102

Expression for Cutis Laxa, Autosomal Recessive, Type Ib

Search GEO for disease gene expression data for Cutis Laxa, Autosomal Recessive, Type Ib.

Pathways for Cutis Laxa, Autosomal Recessive, Type Ib

GO Terms for Cutis Laxa, Autosomal Recessive, Type Ib

Cellular components related to Cutis Laxa, Autosomal Recessive, Type Ib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.13 LOX ELN EFEMP2
2 extracellular matrix GO:0031012 8.62 LOX ELN

Biological processes related to Cutis Laxa, Autosomal Recessive, Type Ib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 elastic fiber assembly GO:0048251 8.62 LOX EFEMP2

Molecular functions related to Cutis Laxa, Autosomal Recessive, Type Ib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 8.62 ELN EFEMP2

Sources for Cutis Laxa, Autosomal Recessive, Type Ib

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