ARCL2A
MCID: CTS038
MIFTS: 35

Cutis Laxa, Autosomal Recessive, Type Iia (ARCL2A)

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 Iia

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

Name: Cutis Laxa, Autosomal Recessive, Type Iia 57 13 40 72
Cutis Laxa with Joint Laxity and Retarded Development 57 75 53 74
Arcl2a 57 12 53 74
Cutis Laxa with Growth and Developmental Delay 57 53 74
Cutis Laxa with Bone Dystrophy 57 53 74
Cutis Laxa, Debre Type 57 53 74
Cutis Laxa with Congenital Disorder of Glycosylation 57 74
Autosomal Recessive Cutis Laxa Type Iia 12 15
Arcl2 57 74
Cutis Laxa, Autosomal Recessive Type 2a 53
Cutis Laxa Autosomal Recessive Type Iia 74
Cutis Laxa, Autosomal Recessive, 2a 74
Cl Type Iia 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
skin abnormalities tend to decrease with age


HPO:

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


Classifications:



External Ids:

Disease Ontology 12 DOID:0070134
MeSH 44 D003483
ICD10 33 Q82.8
MedGen 42 C0268355
UMLS 72 C0268355

Summaries for Cutis Laxa, Autosomal Recessive, Type Iia

OMIM : 57 Autosomal recessive cutis laxa type II represents a spectrum of clinical entities with variable severity of cutis laxa, abnormal growth, developmental delay, and associated skeletal abnormalities. Aside from cutis laxa, persistent wide fontanels, frontal bossing, slight oxycephaly, downward-slanted palpebral fissures, reversed-V eyebrows, and dental caries are characteristic. Patients with ARCL2 can be divided into 2 major groups: ARCL2A, comprising those with a combined N- and O-linked glycosylation defect (CDG type II), and ARCL2B, those without a metabolic disorder (summary by Morava et al., 2009). Van Maldergem et al. (2008) concluded that ARCL2A should be considered more of a multisystem disorder with cobblestone-like brain dysgenesis manifesting as developmental delay and an epileptic neurodegenerative syndrome rather than purely a dermatologic disorder. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (219200)

MalaCards based summary : Cutis Laxa, Autosomal Recessive, Type Iia, also known as cutis laxa with joint laxity and retarded development, is related to atp6v0a2-related cutis laxa and autosomal recessive cutis laxa type 2, and has symptoms including seizures An important gene associated with Cutis Laxa, Autosomal Recessive, Type Iia is ATP6V0A2 (ATPase H+ Transporting V0 Subunit A2), and among its related pathways/superpathways is PI3K-Akt signaling pathway. Affiliated tissues include skin, brain and bone, and related phenotypes are malar flattening and low-set ears

Disease Ontology : 12 An autosomal recessive cutis laxa type II classic type that has material basis in homozygous or compound heterozygous mutations in the ATP6V0A2 gene on chromosome 12q24.

UniProtKB/Swiss-Prot : 74 Cutis laxa, autosomal recessive, 2A: A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Some affected individuals develop seizures and mental deterioration later in life, whereas the skin phenotype tends to become milder with age. At the molecular level, an abnormal glycosylation of serum proteins is observed in many cases.

Wikipedia : 75 De Barsy syndrome is a rare autosomal recessive genetic disorder. Symptoms include cutis laxa (loose... more...

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iia

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



Diseases related to Cutis Laxa, Autosomal Recessive, Type Iia

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

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

32 (show all 38)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 low-set ears 32 HP:0000369
3 frontal bossing 32 HP:0002007
4 high palate 32 HP:0000218
5 intellectual disability 32 HP:0001249
6 seizures 32 HP:0001250
7 muscular hypotonia 32 HP:0001252
8 failure to thrive 32 HP:0001508
9 scoliosis 32 HP:0002650
10 inguinal hernia 32 HP:0000023
11 carious teeth 32 HP:0000670
12 pes planus 32 HP:0001763
13 short nose 32 HP:0003196
14 microcephaly 32 HP:0000252
15 anteverted nares 32 HP:0000463
16 coarse hair 32 HP:0002208
17 feeding difficulties in infancy 32 HP:0008872
18 long philtrum 32 HP:0000343
19 generalized hypotonia 32 HP:0001290
20 strabismus 32 HP:0000486
21 narrow mouth 32 HP:0000160
22 flat face 32 HP:0012368
23 intrauterine growth retardation 32 HP:0001511
24 myopia 32 HP:0000545
25 lipodystrophy 32 HP:0009125
26 motor delay 32 HP:0001270
27 congenital hip dislocation 32 HP:0001374
28 dandy-walker malformation 32 HP:0001305
29 joint hypermobility 32 HP:0001382
30 downslanted palpebral fissures 32 HP:0000494
31 redundant skin 32 HP:0001582
32 midface retrusion 32 HP:0011800
33 wide anterior fontanel 32 HP:0000260
34 polymicrogyria 32 HP:0002126
35 pachygyria 32 HP:0001302
36 brittle hair 32 HP:0002299
37 cutis laxa 32 HP:0000973
38 abnormal isoelectric focusing of serum transferrin 32 HP:0003160

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears

Growth Other:
failure to thrive
intrauterine growth retardation (iugr)

Head And Neck Head:
microcephaly

Head And Neck Face:
long philtrum
flat face
midface hypoplasia

Muscle Soft Tissue:
lipodystrophy
hypotonia
abnormal distribution of subcutaneous fat

Skin Nails Hair Skin:
cutis laxa
loose redundant skin
excessive skin folds

Head And Neck Mouth:
high-arched palate
small mouth

Skeletal:
joint hyperextensibility

Abdomen Gastrointestinal:
feeding problems in infancy

Neurologic Central Nervous System:
seizures
dandy-walker malformation
polymicrogyria
hypotonia
delayed motor development
more
Head And Neck Nose:
short nose
anteverted nares

Skin Nails Hair Hair:
coarse hair
sparse, brittle hair

Head And Neck Eyes:
strabismus
myopia
downslanting palpebral fissures

Skeletal Pelvis:
congenital hip dislocation

Laboratory Abnormalities:
abnormal isoelectric focusing of serum transferrin
defect in n- and o-glycosylation

Skeletal Skull:
large anterior fontanel
delayed closure of the fontanel

Head And Neck Teeth:
dental caries

Skin Nails Hair Skin Histology:
abnormal, broken, shortened elastic fibers
decreased amount of elastin

Clinical features from OMIM:

219200

UMLS symptoms related to Cutis Laxa, Autosomal Recessive, Type Iia:


seizures

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

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

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iia

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iia

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

41
Skin, Brain, Bone, Eye

Publications for Cutis Laxa, Autosomal Recessive, Type Iia

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

(show all 27)
# Title Authors PMID Year
1
Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. 8 71
22773132 2012
2
Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. 8 71
18157129 2008
3
Defective protein glycosylation in patients with cutis laxa syndrome. 8 71
15657616 2005
4
ATP6V0A2-Related Cutis Laxa 38 71
20301755 2009
5
De Barsy syndrome and ATP6V0A2-CDG. 8
20010974 2010
6
Autosomal recessive cutis laxa syndrome revisited. 8
19401719 2009
7
Type II autosomal recessive cutis laxa: report of another patient and molecular studies concerning three candidate genes. 8
18819152 2008
8
Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debre type. 8
18716235 2008
9
Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. 8
17971833 2008
10
Genetic defects in the human glycome. 8
16755287 2006
11
Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. 8
15107842 2004
12
Wrinkly skin syndrome and the syndrome of cutis laxa with growth and developmental delay represent the same disorder. 8
10406678 1999
13
Neurological involvement in a child with the wrinkly skin syndrome. 8
9916839 1999
14
Cutis laxa: a feature of Costello syndrome. 8
7512146 1994
15
Male with type II autosomal recessive cutis laxa. 8
8149651 1994
16
Cutis laxa and the Costello syndrome. 8
8411045 1993
17
Syndrome of congenital cutis laxa with ligamentous laxity and delayed development: report of a brother and sister from Turkey. 8
1700609 1990
18
Facial anomalies in congenital cutis laxa with retarded growth and skeletal dysplasia. 8
2929668 1989
19
Congenital cutis laxa with retardation of growth and development. 8
3669050 1987
20
Congenital cutis laxa with retardation of growth and motor development: a recessive disorder of connective tissue with male lethality. 8
2420495 1986
21
Variable clinical presentation of cutis laxa. 8
4064367 1985
22
Cutis laxa with intrauterine growth retardation and hip dislocation in a male. 8
565809 1978
23
Cutis laxa associated with severe intrauterine growth retardation and congenital dislocation of the hip. 8
5579863 1971
24
A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing 38
30474613 2019
25
[Clinical and genetic analysis of a patient with cutis laxa]. 38
29419872 2018
26
Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica. 38
28294978 2017
27
Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: report of three affected patients. 38
24478233 2014

Variations for Cutis Laxa, Autosomal Recessive, Type Iia

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

6 (show all 17)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ATP6V0A2 NM_012463.4(ATP6V0A2): c.2293C> T (p.Gln765Ter) single nucleotide variant Pathogenic rs80356758 12:124239084-124239084 12:123754537-123754537
2 ATP6V0A2 NM_012463.4(ATP6V0A2): c.187C> T (p.Arg63Ter) single nucleotide variant Pathogenic rs80356750 12:124203239-124203239 12:123718692-123718692
3 ATP6V0A2 NM_012463.4(ATP6V0A2): c.1324G> T (p.Glu442Ter) single nucleotide variant Pathogenic rs80356755 12:124228882-124228882 12:123744335-123744335
4 ATP6V0A2 NM_012463.4(ATP6V0A2): c.2176-3_2176-2del deletion Pathogenic rs367543007 12:124238964-124238965 12:123754417-123754418
5 ATP6V0A2 NM_012463.4(ATP6V0A2): c.294+1G> A single nucleotide variant Pathogenic rs80356751 12:124206996-124206996 12:123722449-123722449
6 ATP6V0A2 NM_012463.4(ATP6V0A2): c.353_354del (p.Leu118fs) deletion Pathogenic rs80356752 12:124209259-124209260 12:123724712-123724713
7 ATP6V0A2 NM_012463.4(ATP6V0A2): c.732-2A> G single nucleotide variant Pathogenic rs80356753 12:124220076-124220076 12:123735529-123735529
8 ATP6V0A2 NM_012463.4(ATP6V0A2): c.840del (p.Glu281fs) deletion Pathogenic rs80356754 12:124221619-124221619 12:123737072-123737072
9 ATP6V0A2 NM_012463.4(ATP6V0A2): c.2356_2362del (p.Gly786fs) deletion Pathogenic 12:124241424-124241430 12:123756877-123756883
10 ATP6V0A2 ATP6V0A2, 1-BP INS, 100A insertion Pathogenic
11 ATP6V0A2 NM_012463.4(ATP6V0A2): c.1929del (p.Gln645fs) deletion Pathogenic/Likely pathogenic rs80356756 12:124233326-124233326 12:123748779-123748779
12 ATP6V0A2 NM_012463.4(ATP6V0A2): c.422G> T (p.Arg141Leu) single nucleotide variant Uncertain significance rs143509747 12:124209328-124209328 12:123724781-123724781
13 ATP6V0A2 NM_012463.4(ATP6V0A2): c.1018C> T (p.Arg340Trp) single nucleotide variant Uncertain significance rs781305219 12:124221798-124221798 12:123737251-123737251
14 ATP6V0A2 NM_012463.4(ATP6V0A2): c.309G> T (p.Lys103Asn) single nucleotide variant Uncertain significance rs144499089 12:124209215-124209215 12:123724668-123724668
15 ATP6V0A2 NM_012463.4(ATP6V0A2): c.614C> T (p.Ala205Val) single nucleotide variant Uncertain significance rs143802431 12:124212422-124212422 12:123727875-123727875
16 ATP6V0A2 NM_012463.4(ATP6V0A2): c.2302G> A (p.Asp768Asn) single nucleotide variant Benign rs367543008 12:124241370-124241370 12:123756823-123756823
17 ATP6V0A2 NM_012463.3(ATP6V0A2): c.*115C> T single nucleotide variant Benign rs367543009 12:124242694-124242694 12:123758147-123758147

Expression for Cutis Laxa, Autosomal Recessive, Type Iia

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

Pathways for Cutis Laxa, Autosomal Recessive, Type Iia

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.46 VWF ATP6V0A2

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iia

Sources for Cutis Laxa, Autosomal Recessive, Type Iia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
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33 ICD10
34 ICD10 via Orphanet
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44 MeSH
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51 NDF-RT
54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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