MCID: ATS393
MIFTS: 38

Autosomal Recessive Cutis Laxa Type I

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

Aliases & Classifications for Autosomal Recessive Cutis Laxa Type I

MalaCards integrated aliases for Autosomal Recessive Cutis Laxa Type I:

Name: Autosomal Recessive Cutis Laxa Type I 12
Autosomal Recessive Cutis Laxa Type 1 12 59
Autosomal Recessive Cutis Laxa with Severe Systemic Involvement 59
Autosomal Recessive Cutis Laxa, Pulmonary Emphysema Type 59
Cutis Laxa, Autosomal Recessive, Type I 73
Cutis Laxa, Autosomal Recessive Type 1 53
Cutis Laxa, Autosomal Recessive 53
Cutis Laxa, Type 1 53
Arcl1 59

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive cutis laxa type 1
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

Classifications:



Summaries for Autosomal Recessive Cutis Laxa Type I

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90349Disease definitionAutosomal recessive cutis laxa, type 1 (ARCL1) is a generalized connective tissue disorder characterized by the association of wrinkled, redundant and sagging inelastic skin with severe systemic manifestations (lung atelectesias and emphysema, vascular anomalies, and gastrointestinal and genitourinary tract diverticuli).EpidemiologyThe prevalence of ARCL1 is unknown but around 60 cases have been reported in the literature so far.Clinical descriptionThe skin manifestations affect the whole body and are usually recognizable from birth. The excessive lax skin is particularly prominent around the axillae, groins and neck and on the face (giving patients an aged appearance with eyelid ptosis and drooping cheeks). Pulmonary emphysema develops early in life (during the neonatal period or by early childhood), often leading to respiratory failure. Common vascular anomalies include arterial aneurysms, fibromuscular artery dysplasia and stenosis leading to progressive heart failure. Genitourinary tract diverticuli lead to vesicoureteral reflux and recurrent infections. Less frequent findings include late closure of the fontanel, joint laxity, hip dislocation, inguinal hernia, arachnodactyly, bone fragility, vascular tortuosity and aortic aneurysm. Intelligence is normal.EtiologyARCL1 is genetically heterogeneous and, although the etiology remains unknown in the majority of cases, mutations have been identified in some patients in the FBLN5 (14q31) and EFEMP2 (11q13) genes, encoding the extracellular matrix proteins fibulin-5 and EGF-containing fibulin-like extracellular matrix protein 2 (Fibulin-4), respectively. Arachnodactyly, bone fragility, vascular tortuosity and aortic aneurysms are common findings in patients carrying EFEMP2 mutations.Diagnostic methodsDetailed clinical evaluation and histological studies of skin biopsies (revealing a moth-eaten appearance, abnormal elastin fiber branching and lose microfibrils associated with reduced elastin synthesis) are usually diagnostic in ARCL1. Molecular testing, available on a research basis only, may confirm the diagnosis in carriers of FBLN5 and EFEMP2 mutations.Differential diagnosisThe differential diagnosis should include other forms of CL (autosomal recessive type 2, autosomal dominant and X-lined CL) and related syndromes (gerodermia osteodysplastica, Cantu syndrome, wrinkly skin syndrome and De Barsy syndrome), together with the Ehlers-Danlos syndromes and Costello syndrome (see these terms).Genetic counselingGenetic counseling should be provided to affected families and prenatal diagnosis through molecular testing is feasible for families in which the disease-causing mutation has been identified.Management and treatmentThere are no effective therapeutic strategies available for ARCL1. Care should be multidisciplinary with symptomatic treatment of pulmonary emphysema, prophylactic therapy for infections and hernia repair.PrognosisThe disease course in ARCL1 is severe, with most patients dying in childhood from cardiac or respiratory failure.Visit the Orphanet disease page for more resources.

MalaCards based summary : Autosomal Recessive Cutis Laxa Type I, also known as autosomal recessive cutis laxa type 1, is related to cutis laxa, autosomal recessive, type ia and cutis laxa. An important gene associated with Autosomal Recessive Cutis Laxa Type I is FBLN5 (Fibulin 5), and among its related pathways/superpathways are Degradation of the extracellular matrix and Elastic fibre formation. Affiliated tissues include skin, lung and bone, and related phenotypes are recurrent urinary tract infections and bladder diverticulum

Disease Ontology : 12 A cutis laxa characterized by wrinkled, redundant and sagging inelastic skin and severe systemic manifestations particulary in the lungs, vasculature, and gastrointestinal and genitourinary systems.

Related Diseases for Autosomal Recessive Cutis Laxa Type I

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



Diseases related to Autosomal Recessive Cutis Laxa Type I

Symptoms & Phenotypes for Autosomal Recessive Cutis Laxa Type I

Human phenotypes related to Autosomal Recessive Cutis Laxa Type I:

59 32 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 recurrent urinary tract infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0000010
2 bladder diverticulum 59 32 hallmark (90%) Very frequent (99-80%) HP:0000015
3 inguinal hernia 59 32 frequent (33%) Frequent (79-30%) HP:0000023
4 vesicoureteral reflux 59 32 occasional (7.5%) Occasional (29-5%) HP:0000076
5 delayed cranial suture closure 59 32 frequent (33%) Frequent (79-30%) HP:0000270
6 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
7 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
8 congenital diaphragmatic hernia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000776
9 hypothyroidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000821
10 osteoporosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000939
11 arachnodactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001166
12 redundant skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001582
13 congestive heart failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0001635
14 pulmonic stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001642
15 emphysema 59 32 hallmark (90%) Very frequent (99-80%) HP:0002097
16 respiratory distress 59 32 occasional (7.5%) Occasional (29-5%) HP:0002098
17 ileus 59 32 frequent (33%) Frequent (79-30%) HP:0002595
18 wormian bones 59 32 occasional (7.5%) Occasional (29-5%) HP:0002645
19 recurrent fractures 59 32 occasional (7.5%) Occasional (29-5%) HP:0002757
20 aortic aneurysm 59 32 frequent (33%) Frequent (79-30%) HP:0004942
21 bowel diverticulosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0005222
22 arterial fibromuscular dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005313
23 joint hyperflexibility 59 32 frequent (33%) Frequent (79-30%) HP:0005692
24 arrhythmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0011675
25 arterial stenosis 59 32 frequent (33%) Frequent (79-30%) HP:0100545
26 premature skin wrinkling 59 32 hallmark (90%) Very frequent (99-80%) HP:0100678
27 atelectasis 59 32 hallmark (90%) Very frequent (99-80%) HP:0100750
28 renal diverticulum 59 32 hallmark (90%) Very frequent (99-80%) HP:0100877
29 cutis laxa 59 Very frequent (99-80%)
30 aneurysm 59 Frequent (79-30%)
31 prematurely aged appearance 59 Very frequent (99-80%)
32 hernia 59 Frequent (79-30%)

MGI Mouse Phenotypes related to Autosomal Recessive Cutis Laxa Type I:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.43 TGFB1 EFEMP2 FBLN5
2 integument MP:0010771 9.33 TGFB1 EFEMP2 FBLN5
3 muscle MP:0005369 9.13 TGFB1 EFEMP2 FBLN5
4 respiratory system MP:0005388 8.8 EFEMP2 FBLN5 TGFB1

Drugs & Therapeutics for Autosomal Recessive Cutis Laxa Type I

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

Genetic Tests for Autosomal Recessive Cutis Laxa Type I

Anatomical Context for Autosomal Recessive Cutis Laxa Type I

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

41
Skin, Lung, Bone, Heart, Testes

Publications for Autosomal Recessive Cutis Laxa Type I

Articles related to Autosomal Recessive Cutis Laxa Type I:

# Title Authors Year
1
Altered TGFbeta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency. ( 20389311 )
2010

Variations for Autosomal Recessive Cutis Laxa Type I

Expression for Autosomal Recessive Cutis Laxa Type I

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

Pathways for Autosomal Recessive Cutis Laxa Type I

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.79 EFEMP2 FBLN5 TGFB1
2
Show member pathways
10.66 EFEMP2 FBLN5 TGFB1

GO Terms for Autosomal Recessive Cutis Laxa Type I

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

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.33 EFEMP2 FBLN5 TGFB1
2 extracellular space GO:0005615 9.13 EFEMP2 FBLN5 TGFB1
3 extracellular matrix GO:0031012 8.62 FBLN5 TGFB1

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

# Name GO ID Score Top Affiliating Genes
1 elastic fiber assembly GO:0048251 8.62 EFEMP2 FBLN5

Sources for Autosomal Recessive Cutis Laxa Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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