ARCL1B
MCID: CTS037
MIFTS: 35

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, Nephrological 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 58 13 74
Arcl1b 58 12 76
Autosomal Recessive Cutis Laxa Type Ib 12 15
Lethal Arteriopathy Syndrome Due to Fibulin-4 Deficiency 60
Cutis Laxa, Autosomal Recessive, Type 1b 41
Cutis Laxa Autosomal Recessive Type Ib 76
Cutis Laxa, Autosomal Recessive, 1b 76

Characteristics:

Orphanet epidemiological data:

60
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:

58
Inheritance:
autosomal recessive

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


HPO:

33
cutis laxa, autosomal recessive, type ib:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cutis Laxa, Autosomal Recessive, Type Ib

UniProtKB/Swiss-Prot : 76 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 efemp2-related cutis laxa and 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, eye and brain, 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 : 58 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:

33 (show all 30)
# Description HPO Frequency HPO Source Accession
1 depressed nasal bridge 33 occasional (7.5%) HP:0005280
2 microcephaly 33 occasional (7.5%) HP:0000252
3 convex nasal ridge 33 occasional (7.5%) HP:0000444
4 oligohydramnios 33 occasional (7.5%) HP:0001562
5 overgrowth 33 occasional (7.5%) HP:0001548
6 bradycardia 33 occasional (7.5%) HP:0001662
7 hypertelorism 33 HP:0000316
8 low-set ears 33 HP:0000369
9 pectus excavatum 33 HP:0000767
10 high palate 33 HP:0000218
11 inguinal hernia 33 HP:0000023
12 prominent forehead 33 HP:0011220
13 emphysema 33 HP:0002097
14 micrognathia 33 HP:0000347
15 abnormality of the pinna 33 HP:0000377
16 arachnodactyly 33 HP:0001166
17 joint hypermobility 33 HP:0001382
18 downslanted palpebral fissures 33 HP:0000494
19 bulbous nose 33 HP:0000414
20 proptosis 33 HP:0000520
21 congenital diaphragmatic hernia 33 HP:0000776
22 generalized hypotonia 33 HP:0001290
23 aortic aneurysm 33 HP:0004942
24 narrow palpebral fissure 33 HP:0045025
25 cutis laxa 33 HP:0000973
26 soft skin 33 HP:0000977
27 pulmonary insufficiency 33 HP:0010444
28 pulmonary artery aneurysm 33 HP:0004937
29 prominence of the premaxilla 33 HP:0010759
30 generalized arterial tortuosity 33 HP:0004955

Symptoms via clinical synopsis from OMIM:

58
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:

42
Skin, Eye, Brain, Bone

Publications for Cutis Laxa, Autosomal Recessive, Type Ib

Variations for Cutis Laxa, Autosomal Recessive, Type Ib

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

76
# 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

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

6 (show top 50) (show all 148)
# Gene Variation Type Significance SNP ID Assembly Location
1 EFEMP2 NM_016938.4(EFEMP2): c.169G> A (p.Glu57Lys) single nucleotide variant Pathogenic rs119489101 GRCh37 Chromosome 11, 65638826: 65638826
2 EFEMP2 NM_016938.4(EFEMP2): c.169G> A (p.Glu57Lys) single nucleotide variant Pathogenic rs119489101 GRCh38 Chromosome 11, 65871355: 65871355
3 EFEMP2 NM_016938.4(EFEMP2): c.835C> T (p.Arg279Cys) single nucleotide variant Pathogenic rs119489102 GRCh37 Chromosome 11, 65635993: 65635993
4 EFEMP2 NM_016938.4(EFEMP2): c.835C> T (p.Arg279Cys) single nucleotide variant Pathogenic rs119489102 GRCh38 Chromosome 11, 65868522: 65868522
5 EFEMP2 NM_016938.4(EFEMP2): c.1070_1073dupCCGC (p.Asp359Argfs) duplication Pathogenic rs193302865 GRCh37 Chromosome 11, 65635429: 65635432
6 EFEMP2 NM_016938.4(EFEMP2): c.1070_1073dupCCGC (p.Asp359Argfs) duplication Pathogenic rs193302865 GRCh38 Chromosome 11, 65867958: 65867961
7 EFEMP2 NM_016938.4(EFEMP2): c.1189G> A (p.Ala397Thr) single nucleotide variant Pathogenic rs193302868 GRCh37 Chromosome 11, 65634532: 65634532
8 EFEMP2 NM_016938.4(EFEMP2): c.1189G> A (p.Ala397Thr) single nucleotide variant Pathogenic rs193302868 GRCh38 Chromosome 11, 65867061: 65867061
9 EFEMP2 NM_016938.4(EFEMP2): c.376G> A (p.Glu126Lys) single nucleotide variant Pathogenic rs193302867 GRCh37 Chromosome 11, 65638121: 65638121
10 EFEMP2 NM_016938.4(EFEMP2): c.376G> A (p.Glu126Lys) single nucleotide variant Pathogenic rs193302867 GRCh38 Chromosome 11, 65870650: 65870650
11 EFEMP2 NM_016938.4(EFEMP2): c.377A> T (p.Glu126Val) single nucleotide variant Pathogenic rs193302869 GRCh37 Chromosome 11, 65638120: 65638120
12 EFEMP2 NM_016938.4(EFEMP2): c.377A> T (p.Glu126Val) single nucleotide variant Pathogenic rs193302869 GRCh38 Chromosome 11, 65870649: 65870649
13 EFEMP2 NM_016938.4(EFEMP2): c.577delC (p.Gln193Serfs) deletion Pathogenic rs193302870 GRCh37 Chromosome 11, 65637622: 65637622
14 EFEMP2 NM_016938.4(EFEMP2): c.577delC (p.Gln193Serfs) deletion Pathogenic rs193302870 GRCh38 Chromosome 11, 65870151: 65870151
15 EFEMP2 NM_016938.4(EFEMP2): c.608A> C (p.Asp203Ala) single nucleotide variant Pathogenic rs193302864 GRCh37 Chromosome 11, 65637447: 65637447
16 EFEMP2 NM_016938.4(EFEMP2): c.608A> C (p.Asp203Ala) single nucleotide variant Pathogenic rs193302864 GRCh38 Chromosome 11, 65869976: 65869976
17 EFEMP2 NM_016938.4(EFEMP2): c.775A> G (p.Ile259Val) single nucleotide variant Benign rs601314 GRCh37 Chromosome 11, 65636053: 65636053
18 EFEMP2 NM_016938.4(EFEMP2): c.775A> G (p.Ile259Val) single nucleotide variant Benign rs601314 GRCh38 Chromosome 11, 65868582: 65868582
19 EFEMP2 NM_016938.4(EFEMP2): c.800G> A (p.Cys267Tyr) single nucleotide variant Pathogenic rs193302866 GRCh37 Chromosome 11, 65636028: 65636028
20 EFEMP2 NM_016938.4(EFEMP2): c.800G> A (p.Cys267Tyr) single nucleotide variant Pathogenic rs193302866 GRCh38 Chromosome 11, 65868557: 65868557
21 EFEMP2 NM_016938.4(EFEMP2): c.679C> T (p.Arg227Cys) single nucleotide variant Pathogenic rs397514683 GRCh37 Chromosome 11, 65637376: 65637376
22 EFEMP2 NM_016938.4(EFEMP2): c.679C> T (p.Arg227Cys) single nucleotide variant Pathogenic rs397514683 GRCh38 Chromosome 11, 65869905: 65869905
23 EFEMP2 NM_016938.4(EFEMP2): c.276C> T (p.His92=) single nucleotide variant Benign rs633800 GRCh37 Chromosome 11, 65638719: 65638719
24 EFEMP2 NM_016938.4(EFEMP2): c.276C> T (p.His92=) single nucleotide variant Benign rs633800 GRCh38 Chromosome 11, 65871248: 65871248
25 EFEMP2 NM_016938.4(EFEMP2): c.368-4G> A single nucleotide variant Benign/Likely benign rs111550973 GRCh38 Chromosome 11, 65870662: 65870662
26 EFEMP2 NM_016938.4(EFEMP2): c.368-4G> A single nucleotide variant Benign/Likely benign rs111550973 GRCh37 Chromosome 11, 65638133: 65638133
27 EFEMP2 NM_016938.4(EFEMP2): c.977G> A (p.Arg326His) single nucleotide variant Uncertain significance rs141868759 GRCh38 Chromosome 11, 65868054: 65868054
28 EFEMP2 NM_016938.4(EFEMP2): c.977G> A (p.Arg326His) single nucleotide variant Uncertain significance rs141868759 GRCh37 Chromosome 11, 65635525: 65635525
29 EFEMP2 NM_016938.4(EFEMP2): c.934A> G (p.Thr312Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs148410446 GRCh38 Chromosome 11, 65868335: 65868335
30 EFEMP2 NM_016938.4(EFEMP2): c.934A> G (p.Thr312Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs148410446 GRCh37 Chromosome 11, 65635806: 65635806
31 EFEMP2 NM_016938.4(EFEMP2): c.1188C> T (p.Ser396=) single nucleotide variant Conflicting interpretations of pathogenicity rs2234473 GRCh38 Chromosome 11, 65867062: 65867062
32 EFEMP2 NM_016938.4(EFEMP2): c.1188C> T (p.Ser396=) single nucleotide variant Conflicting interpretations of pathogenicity rs2234473 GRCh37 Chromosome 11, 65634533: 65634533
33 EFEMP2 NM_016938.4(EFEMP2): c.885C> T (p.Ser295=) single nucleotide variant Conflicting interpretations of pathogenicity rs142509316 GRCh38 Chromosome 11, 65868384: 65868384
34 EFEMP2 NM_016938.4(EFEMP2): c.885C> T (p.Ser295=) single nucleotide variant Conflicting interpretations of pathogenicity rs142509316 GRCh37 Chromosome 11, 65635855: 65635855
35 EFEMP2 NM_016938.4(EFEMP2): c.161-10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs2234461 GRCh38 Chromosome 11, 65871373: 65871373
36 EFEMP2 NM_016938.4(EFEMP2): c.161-10C> T single nucleotide variant Conflicting interpretations of pathogenicity rs2234461 GRCh37 Chromosome 11, 65638844: 65638844
37 EFEMP2 NM_016938.4(EFEMP2): c.139C> T (p.Pro47Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs144320036 GRCh37 Chromosome 11, 65639462: 65639462
38 EFEMP2 NM_016938.4(EFEMP2): c.139C> T (p.Pro47Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs144320036 GRCh38 Chromosome 11, 65871991: 65871991
39 EFEMP2 NM_016938.4(EFEMP2): c.258C> T (p.Ala86=) single nucleotide variant Likely benign rs143873931 GRCh37 Chromosome 11, 65638737: 65638737
40 EFEMP2 NM_016938.4(EFEMP2): c.258C> T (p.Ala86=) single nucleotide variant Likely benign rs143873931 GRCh38 Chromosome 11, 65871266: 65871266
41 EFEMP2 NM_016938.4(EFEMP2): c.277G> A (p.Gly93Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs2234462 GRCh37 Chromosome 11, 65638718: 65638718
42 EFEMP2 NM_016938.4(EFEMP2): c.277G> A (p.Gly93Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs2234462 GRCh38 Chromosome 11, 65871247: 65871247
43 EFEMP2 NM_016938.4(EFEMP2): c.490+9A> T single nucleotide variant Likely benign rs1465424178 GRCh37 Chromosome 11, 65637998: 65637998
44 EFEMP2 NM_016938.4(EFEMP2): c.490+9A> T single nucleotide variant Likely benign rs1465424178 GRCh38 Chromosome 11, 65870527: 65870527
45 EFEMP2 NM_016938.4(EFEMP2): c.1016A> T (p.Gln339Leu) single nucleotide variant Uncertain significance rs754118526 GRCh38 Chromosome 11, 65868015: 65868015
46 EFEMP2 NM_016938.4(EFEMP2): c.1016A> T (p.Gln339Leu) single nucleotide variant Uncertain significance rs754118526 GRCh37 Chromosome 11, 65635486: 65635486
47 EFEMP2 NM_016938.4(EFEMP2): c.396C> T (p.His132=) single nucleotide variant Likely benign rs545330660 GRCh38 Chromosome 11, 65870630: 65870630
48 EFEMP2 NM_016938.4(EFEMP2): c.396C> T (p.His132=) single nucleotide variant Likely benign rs545330660 GRCh37 Chromosome 11, 65638101: 65638101
49 EFEMP2 NM_016938.4(EFEMP2): c.307G> A (p.Ala103Thr) single nucleotide variant Uncertain significance rs1008465800 GRCh38 Chromosome 11, 65871217: 65871217
50 EFEMP2 NM_016938.4(EFEMP2): c.307G> A (p.Ala103Thr) single nucleotide variant Uncertain significance rs1008465800 GRCh37 Chromosome 11, 65638688: 65638688

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 EFEMP2 ELN LOX
2 extracellular matrix GO:0031012 8.62 ELN LOX

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 EFEMP2 LOX

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 EFEMP2 ELN

Sources for Cutis Laxa, Autosomal Recessive, Type Ib

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