ADCL1
MCID: CTS045
MIFTS: 44

Cutis Laxa, Autosomal Dominant 1 (ADCL1)

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 Dominant 1

MalaCards integrated aliases for Cutis Laxa, Autosomal Dominant 1:

Name: Cutis Laxa, Autosomal Dominant 1 57 29 6 72
Cutis Laxa, Autosomal Dominant 57 53 29 6 72
Autosomal Dominant Cutis Laxa 12 53 59 15
Adcl1 57 12 74
Adcl 12 53 59
Autosomal Dominant Cutis Laxa 1 12 15
Cutis Laxa, Autosomal Dominant, Type 1 40
Cutis Laxa, Autosomal Dominant, 1 74

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant cutis laxa
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
onset of skin manifestations from birth to puberty


HPO:

32
cutis laxa, autosomal dominant 1:
Inheritance autosomal dominant inheritance heterogeneous


Classifications:



External Ids:

Disease Ontology 12 DOID:0070130 DOID:0070142
MeSH 44 D003483
ICD10 33 Q82.8
ICD10 via Orphanet 34 Q82.8
UMLS via Orphanet 73 C0268350
Orphanet 59 ORPHA90348
UMLS 72 C0268350 C3276539

Summaries for Cutis Laxa, Autosomal Dominant 1

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90348DefinitionA rare connective tissue disorder characterized by wrinkled, redundant and sagging inelastic skin associated in some cases with internal organ involvement.EpidemiologyThe prevalence of ADCL is unknown but less than 50 cases have been reported in the literature so far.Clinical descriptionPatients are usually diagnosed at birth or in early childhood due to the presence of excessive skin folds and loose, redundant skin. ADCL is considered to be a mild form of cutis laxa with limited systemic involvement although associated features may include hernias, cardiac valve anomalies (redundant mitral and tricuspid valves), cardiovascular manifestations (pulmonary stenosis and aortic and arterial dilatation and tortuosity), gastrointestinal diverticuli and emphysema.EtiologyADCL is genetically heterogeneous: mutations in the elastin gene (ELN; 7q11.1-q21.1) have been reported in some cases, whereas mutations in the gene encoding fibulin-5 (FBLN5; 14q31) have been identified in others. Homozygous mutations in the FBLN5 are associated with the more severe form of CL with extensive systemic involvement, autosomal recessive CL type 1 (ARCL1; see this term).Diagnostic methodsDiagnosis is based on clinical examination, family history and pathognomonic histological findings (sparse, fragmented elastic fibers) on skin biopsies. Molecular testing may allow confirmation of the diagnosis.Differential diagnosisThe differential diagnosis may include other forms of CL (ARC1 and ARCL2, and X-linked CL) and related syndromes (gerodermia osteodysplastica, wrinkly skin syndrome and De Barsy syndrome), together with the Ehlers-Danlos syndromes, Cantu syndrome and Costello syndrome (see these terms).Genetic counselingGenetic counseling should be provided to affected families and prenatal diagnosis may be feasible for families in which the disease-causing mutation has been identified.Management and treatmentThere is no specific treatment for cutis laxa. Management should include symptomatic treatment of any associated manifestations. ADCL is generally a mild cutaneous disease and internal organ involvement is rare.PrognosisMost patients have a good prognosis and life expectancy is usually normal.Visit the Orphanet disease page for more resources.

MalaCards based summary : Cutis Laxa, Autosomal Dominant 1, also known as cutis laxa, autosomal dominant, is related to cutis laxa, autosomal dominant 2 and supravalvular aortic stenosis. An important gene associated with Cutis Laxa, Autosomal Dominant 1 is ELN (Elastin), and among its related pathways/superpathways are Elastic fibre formation and Arginine and proline metabolism. Affiliated tissues include skin, testes and heart, and related phenotypes are redundant skin and premature skin wrinkling

Disease Ontology : 12 An autosomal dominant cutis laxa that has material basis in heterozygous mutations in the ELN gene on chromosome 7q11.

OMIM : 57 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 classic 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). Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. The characteristic loose skin may be accompanied by gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema (summary by Graul-Neumann et al., 2008). Loose, inelastic skin is a clinical feature of many disorders, e.g., geroderma osteodysplasticum (GO; 231070) and Costello syndrome (218040). For a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (123700)

UniProtKB/Swiss-Prot : 74 Cutis laxa, autosomal dominant, 1: 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. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema.

Related Diseases for Cutis Laxa, Autosomal Dominant 1

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
Acquired Cutis Laxa Autosomal Recessive Cutis Laxa Type 2

Diseases related to Cutis Laxa, Autosomal Dominant 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 24)
# Related Disease Score Top Affiliating Genes
1 cutis laxa, autosomal dominant 2 32.3 FBLN5 ELN
2 supravalvular aortic stenosis 30.4 FBLN5 ELN
3 autosomal recessive cutis laxa type iii 30.0 ELN ATP6V0A2 ALDH18A1
4 cutis laxa 29.9 FBLN5 ELN ATP6V0A2 ALDH18A1
5 cutis laxa, autosomal dominant 3 12.8
6 cutis laxa, autosomal recessive, type ia 11.4
7 pulmonary emphysema 10.3
8 ltbp4-related cutis laxa 10.3
9 acquired cutis laxa 10.2 FBLN5 ELN
10 mid-dermal elastolysis 10.2 FBLN5 ELN
11 strabismus 10.1
12 williams-beuren syndrome 10.1
13 wrinkly skin syndrome 10.1
14 scoliosis 10.1
15 inguinal hernia 10.1
16 lung disease 10.1
17 mechanical strabismus 10.1
18 bronchiectasis 10.1
19 7q11.23 duplication syndrome 10.1
20 atp6v0a2-related cutis laxa 10.1
21 efemp2-related cutis laxa 10.1
22 pelvic organ prolapse 10.0 FBLN5 ELN
23 autosomal recessive cutis laxa type i 9.9 FBLN5 ELN ATP6V0A2
24 aortic aneurysm 9.8 FBLN5 ELN

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Dominant 1:



Diseases related to Cutis Laxa, Autosomal Dominant 1

Symptoms & Phenotypes for Cutis Laxa, Autosomal Dominant 1

Human phenotypes related to Cutis Laxa, Autosomal Dominant 1:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 redundant skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001582
2 premature skin wrinkling 59 32 hallmark (90%) Very frequent (99-80%) HP:0100678
3 hypertelorism 59 32 frequent (33%) Frequent (79-30%) HP:0000316
4 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
5 joint hyperflexibility 59 32 frequent (33%) Frequent (79-30%) HP:0005692
6 bowel diverticulosis 59 32 frequent (33%) Frequent (79-30%) HP:0005222
7 inguinal hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000023
8 umbilical hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001537
9 emphysema 59 32 occasional (7.5%) Occasional (29-5%) HP:0002097
10 abnormal heart valve morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001654
11 pulmonic stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001642
12 aortic aneurysm 59 32 occasional (7.5%) Occasional (29-5%) HP:0004942
13 prematurely aged appearance 59 32 Frequent (79-30%) HP:0007495
14 hernia 59 Occasional (29-5%)
15 mitral regurgitation 32 HP:0001653
16 abnormality of the face 32 HP:0000271
17 aortic regurgitation 32 HP:0001659
18 progeroid facial appearance 32 HP:0005328
19 cutis laxa 59 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

57
Genitourinary External Genitalia Male:
inguinal hernia

Skin Nails Hair Skin:
cutis laxa
loose redundant skin
skin lacks elastic recoil
excessive skin folds
no skin hyperelasticity
more
Cardiovascular Heart:
mitral valve regurgitation
aortic valve regurgitation

Respiratory Lung:
emphysema

Head And Neck Face:
premature aged appearance

Skin Nails Hair Skin Histology:
sparse, fragmented elastic fibers

Clinical features from OMIM:

123700

Drugs & Therapeutics for Cutis Laxa, Autosomal Dominant 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Feasibility of Implementing a Mental Health Care Program and Home-based Training for Mothers of Children With Autism Spectrum Disorder in an Urban Population in Bangladesh Recruiting NCT03025646

Search NIH Clinical Center for Cutis Laxa, Autosomal Dominant 1

Genetic Tests for Cutis Laxa, Autosomal Dominant 1

Genetic tests related to Cutis Laxa, Autosomal Dominant 1:

# Genetic test Affiliating Genes
1 Cutis Laxa, Autosomal Dominant 1 29 ELN
2 Cutis Laxa, Autosomal Dominant 29

Anatomical Context for Cutis Laxa, Autosomal Dominant 1

MalaCards organs/tissues related to Cutis Laxa, Autosomal Dominant 1:

41
Skin, Testes, Heart, Lung

Publications for Cutis Laxa, Autosomal Dominant 1

Articles related to Cutis Laxa, Autosomal Dominant 1:

(show all 20)
# Title Authors PMID Year
1
Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene. 8 71
18348261 2008
2
Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. 8 71
16085695 2006
3
Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin. 8 71
15955094 2005
4
Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). 8 71
9873040 1999
5
An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa. 8 71
9580666 1998
6
Congenital cutis laxa with a dominant inheritance and early onset emphysema. 8 71
8091333 1994
7
The dominant and recessive forms of cutis laxa. 8 71
5046633 1972
8
Cutis laxa: autosomal dominant inheritance in five generations. 38 8
1907230 1991
9
Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa. 71
26320891 2015
10
FBLN5-Related Cutis Laxa 71
20301756 2009
11
Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene. 71
12618961 2003
12
New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV. 71
9643297 1998
13
Transforming growth factor-beta reverses a posttranscriptional defect in elastin synthesis in a cutis laxa skin fibroblast strain. 71
7884000 1995
14
Heterogeneity of elastin expression in cutis laxa fibroblast strains. 8
2745999 1989
15
Acquired cutis laxa concomitant with nephrotic syndrome. 8
3307640 1987
16
A familial cutis laxa syndrome with ultrastructural abnormalities of collagen and elastin. 8
7430706 1980
17
Generalized elastolysis (cutis laxa). 8
707540 1978
18
Cutis hyperelastica (Ehlers-Danlos) and cutis laxa. 8
13973774 1963
19
Ehlers-Danlos syndrome and cutis laxa: an account of families in the Oxford area. 8
13910947 1962
20
Cutis laxa. 8
13748595 1961

Variations for Cutis Laxa, Autosomal Dominant 1

ClinVar genetic disease variations for Cutis Laxa, Autosomal Dominant 1:

6 (show top 50) (show all 82)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ELN ELN, 1-BP DEL, 2012G deletion Pathogenic
2 ELN ELN, 1-BP DEL, 748A deletion Pathogenic
3 ELN ELN, 1-BP DEL, 2039C deletion Pathogenic
4 ELN ELN, EX9-33DUP duplication Pathogenic
5 ELN ELN, 25-BP DEL, NT2114 deletion Pathogenic
6 ELN ELN, 1-BP DEL, 2159C deletion Pathogenic
7 ELN ELN, 1621C-T single nucleotide variant Pathogenic
8 FBLN5 NM_006329.3(FBLN5): c.380-9061_873dup duplication Pathogenic 14:92347752-92370477 14:91881408-91904133
9 ELN NM_000501.4(ELN): c.1150+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs727503030 7:73469100-73469100 7:74054770-74054770
10 ELN NM_000501.4(ELN): c.2161del (p.Arg721fs) deletion Likely pathogenic rs794729201 7:73483015-73483015 7:74068685-74068685
11 ELN NM_000501.4(ELN): c.659C> T (p.Pro220Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs201012726 7:73462020-73462020 7:74047690-74047690
12 ELN NM_000501.4(ELN): c.470-10C> G single nucleotide variant Conflicting interpretations of pathogenicity rs200663056 7:73459542-73459542 7:74045212-74045212
13 ELN NM_000501.4(ELN): c.328G> A (p.Ala110Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs137953195 7:73457316-73457316 7:74042986-74042986
14 ELN NM_000501.4(ELN): c.930C> T (p.Ala310=) single nucleotide variant Conflicting interpretations of pathogenicity rs147367888 7:73466294-73466294 7:74051964-74051964
15 ELN NM_000501.4(ELN): c.2077C> T (p.Pro693Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs369804770 7:73480318-73480318 7:74065988-74065988
16 ELN NM_000501.4(ELN): c.1339G> A (p.Ala447Thr) single nucleotide variant Uncertain significance rs139335797 7:73471025-73471025 7:74056695-74056695
17 ELN NM_000501.4(ELN): c.*629T> C single nucleotide variant Uncertain significance rs776424755 7:73483659-73483659 7:74069329-74069329
18 ELN NM_000501.4(ELN): c.*1062dup duplication Uncertain significance rs574934142 7:73484092-73484092 7:74069762-74069762
19 ELN NM_001278918.1(ELN): c.-70G> C single nucleotide variant Uncertain significance rs537200597 7:73442448-73442448 7:74028118-74028118
20 ELN NM_000501.3(ELN): c.1096+45_1096+50dupGTGTGT duplication Uncertain significance rs10579871 7:73467684-73467689 7:74053354-74053359
21 ELN NM_000501.3(ELN): c.1096+49_1096+50dupGT duplication Uncertain significance rs10579871 7:73467688-73467689 7:74053358-74053359
22 ELN NM_000501.4(ELN): c.1234G> A (p.Gly412Arg) single nucleotide variant Uncertain significance rs375116795 7:73470684-73470684 7:74056354-74056354
23 ELN NM_000501.4(ELN): c.*489G> T single nucleotide variant Uncertain significance rs886062432 7:73483519-73483519 7:74069189-74069189
24 ELN NM_000501.4(ELN): c.*997G> T single nucleotide variant Uncertain significance rs886062434 7:73484027-73484027 7:74069697-74069697
25 ELN NM_000501.4(ELN): c.163+13A> G single nucleotide variant Uncertain significance rs782388951 7:73450927-73450927 7:74036597-74036597
26 ELN NM_000501.4(ELN): c.*251C> T single nucleotide variant Uncertain significance rs886062430 7:73483281-73483281 7:74068951-74068951
27 ELN NM_000501.4(ELN): c.*458C> T single nucleotide variant Uncertain significance rs886062431 7:73483488-73483488 7:74069158-74069158
28 ELN NM_000501.3(ELN): c.1096+47_1096+50dupGTGT duplication Uncertain significance rs10579871 7:73467686-73467689 7:74053356-74053359
29 ELN NM_000501.3(ELN): c.1096+49_1096+50delGT deletion Uncertain significance rs10579871 7:73467688-73467689 7:74053358-74053359
30 ELN NM_000501.4(ELN): c.1281C> T (p.Pro427=) single nucleotide variant Uncertain significance rs376496267 7:73470731-73470731 7:74056401-74056401
31 ELN NM_000501.4(ELN): c.326G> A (p.Gly109Asp) single nucleotide variant Uncertain significance rs145519139 7:73457314-73457314 7:74042984-74042984
32 ELN NM_000501.4(ELN): c.647G> T (p.Gly216Val) single nucleotide variant Uncertain significance rs145612009 7:73462008-73462008 7:74047678-74047678
33 ELN NM_000501.4(ELN): c.1943G> A (p.Gly648Glu) single nucleotide variant Uncertain significance rs140085632 7:73477975-73477975 7:74063645-74063645
34 ELN NM_000501.4(ELN): c.1675G> A (p.Val559Ile) single nucleotide variant Uncertain significance rs560081099 7:73474759-73474759 7:74060429-74060429
35 ELN NM_000501.4(ELN): c.*794C> T single nucleotide variant Uncertain significance rs185988110 7:73483824-73483824 7:74069494-74069494
36 ELN NM_000501.4(ELN): c.*570G> A single nucleotide variant Uncertain significance rs565400803 7:73483600-73483600 7:74069270-74069270
37 ELN NM_000501.4(ELN): c.*663C> T single nucleotide variant Uncertain significance rs886062433 7:73483693-73483693 7:74069363-74069363
38 ELN NM_000501.4(ELN): c.*1145dup duplication Uncertain significance rs886062436 7:73484175-73484175 7:74069845-74069845
39 ELN NM_000501.4(ELN): c.1358-199G> A single nucleotide variant Uncertain significance 7:73471771-73471771 7:74057441-74057441
40 ELN NM_000501.4(ELN): c.*1195C> T single nucleotide variant Likely benign rs115872030 7:73484225-73484225 7:74069895-74069895
41 ELN NM_000501.4(ELN): c.1232T> G (p.Val411Gly) single nucleotide variant Likely benign rs200180992 7:73470682-73470682 7:74056352-74056352
42 ELN NM_000501.4(ELN): c.1338C> T (p.Ala446=) single nucleotide variant Likely benign rs146576615 7:73471024-73471024 7:74056694-74056694
43 ELN NM_000501.4(ELN): c.1909G> A (p.Ala637Thr) single nucleotide variant Likely benign rs536177240 7:73477690-73477690 7:74063360-74063360
44 ELN NM_000501.4(ELN): c.*172G> A single nucleotide variant Likely benign rs56120764 7:73483202-73483202 7:74068872-74068872
45 ELN NM_000501.4(ELN): c.1269C> G (p.Val423=) single nucleotide variant Likely benign rs61734583 7:73470719-73470719 7:74056389-74056389
46 ELN NM_000501.4(ELN): c.2132G> A (p.Gly711Asp) single nucleotide variant Likely benign rs41511151 7:73482987-73482987 7:74068657-74068657
47 ELN NM_000501.4(ELN): c.1622-13C> T single nucleotide variant Likely benign rs41362346 7:73474693-73474693 7:74060363-74060363
48 ELN NM_000501.4(ELN): c.1999C> T (p.Pro667Ser) single nucleotide variant Likely benign rs142316834 7:73480029-73480029 7:74065699-74065699
49 ELN NM_000501.4(ELN): c.1821G> C (p.Gly607=) single nucleotide variant Likely benign rs144835575 7:73477517-73477517 7:74063187-74063187
50 ELN NM_000501.4(ELN): c.*95C> T single nucleotide variant Likely benign rs181078432 7:73483125-73483125 7:74068795-74068795

Expression for Cutis Laxa, Autosomal Dominant 1

Search GEO for disease gene expression data for Cutis Laxa, Autosomal Dominant 1.

Pathways for Cutis Laxa, Autosomal Dominant 1

Pathways related to Cutis Laxa, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.02 FBLN5 ELN
2
Show member pathways
10.71 CKB ALDH18A1
3
Show member pathways
10 CKB ALDH18A1

GO Terms for Cutis Laxa, Autosomal Dominant 1

Cellular components related to Cutis Laxa, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 elastic fiber GO:0071953 8.62 FBLN5 ELN

Molecular functions related to Cutis Laxa, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.61 LIF KIR3DL2 FBLN5 ELN CKB CHRNA5
2 extracellular matrix constituent conferring elasticity GO:0030023 8.62 FBLN5 ELN

Sources for Cutis Laxa, Autosomal Dominant 1

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