ARCL1A
MCID: CTS030
MIFTS: 45

Cutis Laxa, Autosomal Recessive, Type Ia (ARCL1A)

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 Ia

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

Name: Cutis Laxa, Autosomal Recessive, Type Ia 56 13 39
Autosomal Recessive Cutis Laxa Type Ia 12 29 6 15
Arcl1a 56 12 73
Cutis Laxa, Autosomal Recessive 56 29
Cutis Laxa, Autosomal Recessive, Type I 71
Cutis Laxa Autosomal Recessive Type Ia 73
Cutis Laxa Autosomal Recessive Type I 73
Cutis Laxa, Autosomal Recessive, 1a 73
Cl Type I 73
Arcl1 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity


HPO:

31
cutis laxa, autosomal recessive, type ia:
Inheritance autosomal recessive inheritance heterogeneous


Classifications:



Summaries for Cutis Laxa, Autosomal Recessive, Type Ia

OMIM : 56 Cutis laxa is a collection of disorders that are typified by loose and/or wrinkled skin that imparts a prematurely aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The skin lacks elastic recoil, in marked contrast to the hyperelasticity apparent in classical Ehlers-Danlos syndrome (see 130000). These properties are nearly always attributable to loss, fragmentation, or severe disorganization of dermal elastic fibers (summary by Davidson and Giro, 2002). The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa (ARCL1) is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. Diminution of elastic fibers throughout the dermis and abnormal elastin components by electron microscopy are pathognomonic (summary by Morava et al., 2009). Classification of autosomal recessive cutis laxa is further divided into type II (ARCL2), associated with bone dystrophy, joint laxity, and developmental delay; and type III (ARCL3), or de Barsy syndrome, which presents very severe symptoms, with ocular involvement and mental retardation (summary by Davidson and Giro, 2002). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant cutis laxa, see 123700. (219100)

MalaCards based summary : Cutis Laxa, Autosomal Recessive, Type Ia, also known as autosomal recessive cutis laxa type ia, is related to cutis laxa, autosomal recessive, type iiib and cutis laxa, autosomal recessive, type iiia. An important gene associated with Cutis Laxa, Autosomal Recessive, Type Ia is FBLN5 (Fibulin 5), and among its related pathways/superpathways are Degradation of the extracellular matrix and Amino acid synthesis and interconversion (transamination). Affiliated tissues include skin, lung and bone, and related phenotypes are inguinal hernia and recurrent respiratory infections

Disease Ontology : 12 An autosomal recessive cutis laxa type I that has material basis in homozygous or compound heterozygous mutation in the FBLN5 gene on chromosome 14q32.

UniProtKB/Swiss-Prot : 73 Cutis laxa, autosomal recessive, 1A: 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. Type I autosomal recessive cutis laxa is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon.

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Ia

Diseases in the Cutis Laxa family:

Cutis Laxa, Autosomal Dominant 1 Cutis Laxa, Autosomal Recessive, Type Ia
Cutis Laxa, Autosomal Recessive, Type Iiia Cutis Laxa, Autosomal Recessive, Type Iia
Cutis Laxa, Autosomal Recessive, Type Iib Cutis Laxa, Autosomal Recessive, Type Ic
Cutis Laxa, Autosomal Dominant 2 Cutis Laxa, Autosomal Recessive, Type Ib
Cutis Laxa, Autosomal Recessive, Type Iiib Cutis Laxa, Autosomal Dominant 3
Cutis Laxa, Autosomal Recessive, Type Iic Cutis Laxa, Autosomal Recessive, Type Iid
Autosomal Recessive Cutis Laxa Type Iii Autosomal Recessive Cutis Laxa Type I
Atp6v0a2-Related Cutis Laxa Efemp2-Related Cutis Laxa
Fbln5-Related Cutis Laxa Ltbp4-Related Cutis Laxa
Acquired Cutis Laxa Autosomal Recessive Cutis Laxa Type 2

Diseases related to Cutis Laxa, Autosomal Recessive, Type Ia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 55)
# Related Disease Score Top Affiliating Genes
1 cutis laxa, autosomal recessive, type iiib 33.1 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2 ALDH18A1
2 cutis laxa, autosomal recessive, type iiia 32.8 RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
3 cutis laxa, autosomal dominant 1 30.6 SLC2A10 FBN1 FBLN5 EFEMP2 ALDH18A1
4 cutis laxa, autosomal recessive, type iid 30.5 RIN2 LTBP4 GORAB ATP6V1E1 ATP6V0A2
5 autosomal recessive cutis laxa type i 29.9 SLC2A10 RIN2 PYCR1 LTBP4 GORAB FBN1
6 cutis laxa, autosomal recessive, type ib 29.9 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
7 cutis laxa, autosomal recessive, type ic 29.9 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
8 cutis laxa, autosomal recessive, type iib 29.9 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
9 cutis laxa, autosomal recessive, type iia 28.9 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
10 cutis laxa 26.6 RIN2 PYCR1 LTBP4 LOXL1 GORAB FBN1
11 atp6v0a2-related cutis laxa 11.7
12 efemp2-related cutis laxa 11.7
13 cutis laxa, autosomal dominant 3 11.2
14 cutis laxa, autosomal recessive, type iic 11.2
15 wrinkly skin syndrome 10.3
16 doyne honeycomb retinal dystrophy 10.2 FBLN5 EFEMP2
17 macs syndrome 10.2 RIN2 FBLN5
18 borderline glaucoma 10.2 PYCR1 GORAB
19 alacrima, achalasia, and mental retardation syndrome 10.1
20 bone disease 10.1
21 pulmonary emphysema 10.1
22 fbln5-related cutis laxa 10.1
23 mid-dermal elastolysis 10.1 FBN1 FBLN5
24 spastic paraplegia 9b, autosomal recessive 10.1 PYCR1 ALDH18A1
25 spastic paraplegia 9a, autosomal dominant 10.1 PYCR1 ALDH18A1
26 neu-laxova syndrome 2 10.0 PYCR1 ALDH18A1
27 hyperprolinemia 10.0 PYCR1 ALDH18A1
28 diaphragmatic eventration 10.0 LTBP4 FBN1
29 aortic valve insufficiency 9.9 FBN1 EFEMP2
30 ureteric orifice cancer 9.9 FBN1 FBLN5 EFEMP2
31 isolated ectopia lentis 9.9 LTBP4 FBN1
32 supravalvular aortic stenosis 9.9 FBN1 FBLN5 EFEMP2
33 aortic aneurysm, familial thoracic 2 9.9 SLC2A10 FBN1
34 loeys-dietz syndrome 4 9.8 SLC2A10 FBN1
35 lens subluxation 9.7 LOXL1 FBN1
36 costello syndrome 9.7 FBN1 FBLN5
37 loeys-dietz syndrome 1 9.7 SLC2A10 FBN1
38 phacogenic glaucoma 9.7 LOXL1 FBN1 FBLN5
39 loeys-dietz syndrome 3 9.7 SLC2A10 FBN1 EFEMP2
40 pelvic organ prolapse 9.7 LOXL1 FBN1 FBLN5
41 iris disease 9.7 LOXL1 FBN1
42 inguinal hernia 9.7 LOXL1 FBN1 FBLN5
43 bladder diverticulum 9.6 SLC2A10 LTBP4 EFEMP2 ATP6V0A2
44 primary congenital glaucoma 9.6 LOXL1 FBN1
45 tricuspid valve prolapse 9.5 SLC2A10 FBN1 FBLN5 EFEMP2
46 aortic aneurysm, familial thoracic 1 9.5 SLC2A10 FBN1 FBLN5 EFEMP2
47 aortic aneurysm 9.5 SLC2A10 FBN1 FBLN5 EFEMP2
48 loeys-dietz syndrome 9.5 SLC2A10 FBN1 FBLN5 EFEMP2
49 arterial tortuosity syndrome 9.3 SLC2A10 LTBP4 FBN1 FBLN5 EFEMP2
50 scoliosis 9.2 RIN2 LTBP4 LOXL1 FBN1 FBLN5

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



Diseases related to Cutis Laxa, Autosomal Recessive, Type Ia

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

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

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 inguinal hernia 31 HP:0000023
2 recurrent respiratory infections 31 HP:0002205
3 umbilical hernia 31 HP:0001537
4 microcephaly 31 HP:0000252
5 emphysema 31 HP:0002097
6 pectus excavatum 31 HP:0000767
7 joint laxity 31 HP:0001388
8 abnormality of the face 31 HP:0000271
9 arachnodactyly 31 HP:0001166
10 bladder diverticulum 31 HP:0000015
11 redundant skin 31 HP:0001582
12 supravalvular aortic stenosis 31 HP:0004381
13 congenital diaphragmatic hernia 31 HP:0000776
14 oligohydramnios 31 HP:0001562
15 overgrowth 31 HP:0001548
16 ascending tubular aorta aneurysm 31 HP:0004970
17 vascular tortuosity 31 HP:0004948

Symptoms via clinical synopsis from OMIM:

56
Genitourinary External Genitalia Male:
inguinal hernia

Respiratory:
recurrent respiratory infections

Respiratory Lung:
emphysema

Skeletal:
joint laxity
congenital fractures

Cardiovascular Heart:
supravalvular aortic stenosis

Skin Nails Hair Skin:
cutis laxa
loose redundant skin
excessive skin folds
no skin hyperelasticity
normal wound healing

Genitourinary Bladder:
bladder diverticula

Chest Diaphragm:
diaphragmatic hernia

Head And Neck Face:
sagging cheeks

Genitourinary External Genitalia Female:
inguinal hernia

Head And Neck Head:
microcephaly

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Skeletal Hands:
arachnodactyly

Prenatal Manifestations Amniotic Fluid:
oligohydramnios

Cardiovascular Vascular:
vascular tortuosity
ascending aortic aneurysm

Abdomen External Features:
umbilical hernias

Growth Height:
fetal overgrowth

Skin Nails Hair Skin Histology:
increased vascularization, reduced collagen bundle size
underdeveloped elastic fibers in dermis

Clinical features from OMIM:

219100

MGI Mouse Phenotypes related to Cutis Laxa, Autosomal Recessive, Type Ia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.56 ALDH18A1 ATP6V0A2 EFEMP2 FBLN5 FBN1 GORAB
2 respiratory system MP:0005388 9.17 EFEMP2 FBLN5 FBN1 GORAB LOXL1 LTBP4

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

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

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Ia

Genetic tests related to Cutis Laxa, Autosomal Recessive, Type Ia:

# Genetic test Affiliating Genes
1 Autosomal Recessive Cutis Laxa Type Ia 29 FBLN5
2 Cutis Laxa, Autosomal Recessive 29

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Ia

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

40
Skin, Lung, Bone

Publications for Cutis Laxa, Autosomal Recessive, Type Ia

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

(show all 27)
# Title Authors PMID Year
1
Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. 6 56
22829427 2013
2
Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa. 6 56
17035250 2006
3
Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. 6 56
12189163 2002
4
Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs. 56 6
3232707 1988
5
Autosomal recessive cutis laxa syndrome revisited. 56
19401719 2009
6
FBLN5-Related Cutis Laxa 6
20301756 2009
7
A p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model. 6
18185537 2008
8
Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa. 56
16652333 2006
9
A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa. 56
12707960 2003
10
Congenital cutis laxa and lysyl oxidase deficiency. 56
9111998 1997
11
Cutis laxa with ultrastructural abnormalities of elastic fiber. 56
2754071 1989
12
Cutis laxa: reduced elastin gene expression in skin fibroblast cultures as determined by hybridizations with a homologous cDNA and an exon 1-specific oligonucleotide. 56
3360789 1988
13
Variable clinical presentation of cutis laxa. 56
4064367 1985
14
Characterization and partial purification of a neutral protease from the serum of a patient with autosomal recessive pulmonary emphysema and cutis laxa. 56
3886813 1985
15
Association of hemolytic anemia and early-onset pulmonary emphysema in three siblings. 56
6747755 1984
16
Two forms of cutis laxa presenting in the newborn period. 56
102106 1978
17
A syndrome of generalized elastic fiber deficiency with leprechaunoid features: a distinct genetic disease with an autosomal recessive mode of inheritance. 56
949858 1976
18
The dominant and recessive forms of cutis laxa. 56
5046633 1972
19
Plastic surgery in cutis laxa. 56
5469601 1970
20
Cutis laxa. 56
5773419 1969
21
Congenital cutis laxa with advanced cardiopulmonary disease. 56
5658618 1968
22
Cutis laxa associated with pulmonary artery stenosis. 56
5647293 1968
23
Cutis laxa. A manifestation of generalized elastolysis. 56
5835325 1965
24
Ehlers-Danlos syndrome and cutis laxa: an account of families in the Oxford area. 56
13910947 1962
25
Cutis laxa. 56
13748595 1961
26
[Not Available]. 56
13237122 1954
27
Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation. 61
24962763 2014

Variations for Cutis Laxa, Autosomal Recessive, Type Ia

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

6 (show all 18) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FBLN5 NM_006329.3(FBLN5):c.1201_1202del (p.Ser401fs)deletion Pathogenic 689758 14:92336713-92336714 14:91870369-91870370
2 EFEMP2 NM_016938.5(EFEMP2):c.169G>A (p.Glu57Lys)SNV Pathogenic 5423 rs119489101 11:65638826-65638826 11:65871355-65871355
3 EFEMP2 NM_016938.5(EFEMP2):c.835C>T (p.Arg279Cys)SNV Pathogenic 5424 rs119489102 11:65635993-65635993 11:65868522-65868522
4 EFEMP2 NM_016938.5(EFEMP2):c.1070_1073dup (p.Asp359fs)duplication Pathogenic 5425 rs193302865 11:65635428-65635429 11:65867957-65867958
5 FBLN5 NM_006329.3(FBLN5):c.679T>C (p.Ser227Pro)SNV Pathogenic 5475 rs28939370 14:92353597-92353597 14:91887253-91887253
6 FBLN5 NM_006329.3(FBLN5):c.1171G>T (p.Glu391Ter)SNV Pathogenic 21451 rs80338767 14:92343845-92343845 14:91877501-91877501
7 FBLN5 NM_006329.3(FBLN5):c.649T>C (p.Cys217Arg)SNV Pathogenic 21454 rs80338766 14:92353627-92353627 14:91887283-91887283
8 EFEMP2 NM_016938.5(EFEMP2):c.1189G>A (p.Ala397Thr)SNV Pathogenic 39009 rs193302868 11:65634532-65634532 11:65867061-65867061
9 EFEMP2 NM_016938.5(EFEMP2):c.376G>A (p.Glu126Lys)SNV Pathogenic 39011 rs193302867 11:65638121-65638121 11:65870650-65870650
10 EFEMP2 NM_016938.5(EFEMP2):c.377A>T (p.Glu126Val)SNV Pathogenic 39012 rs193302869 11:65638120-65638120 11:65870649-65870649
11 EFEMP2 NM_016938.5(EFEMP2):c.577del (p.Gln193fs)deletion Pathogenic 39013 rs193302870 11:65637622-65637622 11:65870151-65870151
12 EFEMP2 NM_016938.5(EFEMP2):c.608A>C (p.Asp203Ala)SNV Pathogenic 39014 rs193302864 11:65637447-65637447 11:65869976-65869976
13 EFEMP2 NM_016938.5(EFEMP2):c.800G>A (p.Cys267Tyr)SNV Pathogenic 39016 rs193302866 11:65636028-65636028 11:65868557-65868557
14 FBLN5 NM_006329.3(FBLN5):c.604G>A (p.Gly202Arg)SNV Conflicting interpretations of pathogenicity 21453 rs80338765 14:92357580-92357580 14:91891236-91891236
15 FBLN5 NM_006329.3(FBLN5):c.1183C>T (p.Arg395Trp)SNV Uncertain significance 417872 rs372650987 14:92343833-92343833 14:91877489-91877489
16 EFEMP2 NM_016938.5(EFEMP2):c.775A>G (p.Ile259Val)SNV Benign 39015 rs601314 11:65636053-65636053 11:65868582-65868582
17 EFEMP2 NM_016938.5(EFEMP2):c.1226G>A (p.Arg409Gln)SNV Benign 39010 rs61893867 11:65634495-65634495 11:65867024-65867024
18 FBLN5 NM_006329.3(FBLN5):c.1090G>T (p.Asp364Tyr)SNV Benign 21450 rs1802492 14:92343926-92343926 14:91877582-91877582

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

73
# Symbol AA change Variation ID SNP ID
1 FBLN5 p.Ser227Pro VAR_017153 rs28939370
2 FBLN5 p.Cys217Arg VAR_072392 rs80338766
3 FBLN5 p.Gly267Ser VAR_072393 rs149396611

Expression for Cutis Laxa, Autosomal Recessive, Type Ia

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

Pathways for Cutis Laxa, Autosomal Recessive, Type Ia

Pathways related to Cutis Laxa, Autosomal Recessive, Type Ia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.01 LTBP4 LOXL1 FBN1 FBLN5 EFEMP2
2
Show member pathways
10.88 PYCR1 ALDH18A1
3
Show member pathways
10.88 LTBP4 LOXL1 FBN1 FBLN5 EFEMP2
4
Show member pathways
10.54 PYCR1 ALDH18A1

GO Terms for Cutis Laxa, Autosomal Recessive, Type Ia

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

# Name GO ID Score Top Affiliating Genes
1 basement membrane GO:0005604 9.33 LOXL1 FBN1 EFEMP2
2 extracellular matrix GO:0031012 9.26 LTBP4 LOXL1 FBN1 FBLN5
3 collagen-containing extracellular matrix GO:0062023 9.02 LTBP4 LOXL1 FBN1 FBLN5 EFEMP2

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 9.61 LOXL1 FBN1 FBLN5
2 proton transmembrane transport GO:1902600 9.43 SLC2A10 ATP6V1E1 ATP6V0A2
3 cellular amino acid biosynthetic process GO:0008652 9.4 PYCR1 ALDH18A1
4 transferrin transport GO:0033572 9.37 ATP6V1E1 ATP6V0A2
5 phagosome acidification GO:0090383 9.32 ATP6V1E1 ATP6V0A2
6 elastic fiber assembly GO:0048251 9.16 FBLN5 EFEMP2
7 L-proline biosynthetic process GO:0055129 8.96 PYCR1 ALDH18A1
8 proline biosynthetic process GO:0006561 8.62 PYCR1 ALDH18A1

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

# Name GO ID Score Top Affiliating Genes
1 calcium ion binding GO:0005509 9.62 LTBP4 FBN1 FBLN5 EFEMP2
2 integrin binding GO:0005178 9.33 LTBP4 FBN1 FBLN5
3 proton-transporting ATPase activity, rotational mechanism GO:0046961 9.26 ATP6V1E1 ATP6V0A2
4 extracellular matrix structural constituent GO:0005201 9.13 LTBP4 FBN1 EFEMP2
5 extracellular matrix constituent conferring elasticity GO:0030023 8.62 FBN1 FBLN5

Sources for Cutis Laxa, Autosomal Recessive, Type Ia

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