PPKCA1
MCID: PLM158
MIFTS: 42

Palmoplantar Keratoderma and Congenital Alopecia 1 (PPKCA1)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Palmoplantar Keratoderma and Congenital Alopecia 1

MalaCards integrated aliases for Palmoplantar Keratoderma and Congenital Alopecia 1:

Name: Palmoplantar Keratoderma and Congenital Alopecia 1 57 12 73 15
Autosomal Dominant Palmoplantar Hyperkeratosis and Congenital Alopecia 12 20 58
Autosomal Dominant Palmoplantar Keratoderma and Congenital Alopecia 12 20 58
Palmoplantar Keratoderma and Congenital Alopecia, Stevanovic Type 12 20 58
Keratoderma-Hypotrichosis-Leukonychia Totalis Syndrome 57 12 73
Ppk-Ca, Stevanovic Type 12 20 58
Ppkca1 57 12 73
Alopecia Congenita with Hyperkeratosis of the Palms and Soles 20 6
Ppkca, Stevanovic Type 57 73
Keratoderma, Palmoplantar, with Congenital Alopecia, Type 1 39
Palmoplantar Keratoderma with Congenital Alopecia 57
Alopecia Congenita Keratosis Palmoplantaris 44
Ppkca Stevanovic Type 12

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant palmoplantar keratoderma and congenital alopecia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy


HPO:

31
palmoplantar keratoderma and congenital alopecia 1:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0111244
OMIM® 57 104100
ICD10 via Orphanet 33 Q82.8
UMLS via Orphanet 72 C1863093
Orphanet 58 ORPHA1010
UMLS 71 C1863093

Summaries for Palmoplantar Keratoderma and Congenital Alopecia 1

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1010DefinitionA rare genetic skin disorder characterized by absence of scalp and body hair and palmoplantar keratoderma, without other hand complications.EpidemiologyTo date, ten individuals with a clinical diagnosis of autosomal dominant palmoplantar keratoderma and congenital alopecia (PPK-CA) have been reported.Clinical descriptionAutosomal dominant PPK-CA usually presents during infancy. Its very early onset is often characterized by fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features which appear in the following years. Palmoplantar keratoderma develops during infancy and may have an unusual pattern, affecting the two sides of fingers and palms, but usually sparing the palmar sides. Periungueal involvement is typical, leading to secondary nail dystrophy. Autosomal dominant PPK-CA seems to have a more benign course than autosomal recessive PPK-CA (see this term).EtiologyThe genetic basis of autosomal dominant PPK-CA is unknown. Transmission appears to be autosomal dominant.Genetic counselingTransmission appears to be autosomal dominant.Visit the Orphanet disease page for more resources.

MalaCards based summary : Palmoplantar Keratoderma and Congenital Alopecia 1, also known as autosomal dominant palmoplantar hyperkeratosis and congenital alopecia, is related to hypotrichosis and keratosis. An important gene associated with Palmoplantar Keratoderma and Congenital Alopecia 1 is GJA1 (Gap Junction Protein Alpha 1), and among its related pathways/superpathways are Vesicle-mediated transport and G-Beta Gamma Signaling. Affiliated tissues include skin, and related phenotypes are palmoplantar keratoderma and palmoplantar hyperkeratosis

Disease Ontology : 12 An ectodermal dysplasia characterized by autosomal dominant inheritance of severe hyperkeratosis, congenital alopecia, and in some patients nail anomalies that has material basis in heterozygous mutation in GJA1 on 6q22.31.

OMIM® : 57 Palmoplantar keratoderma and congenital alopecia-1 (PPKCA1) is a rare autosomal dominant disorder characterized by severe hyperkeratosis and congenital alopecia. Nail changes occur in some patients (summary by Castori et al., 2010). Also see PPKCA2 (212360), an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation. (104100) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : 73 Palmoplantar keratoderma and congenital alopecia 1: A rare autosomal dominant disorder characterized by severe hyperkeratosis of the palms and soles, and congenital hypotrichosis or alopecia. Dystrophic nail changes occur in some patients.

Related Diseases for Palmoplantar Keratoderma and Congenital Alopecia 1

Diseases in the Palmoplantar Keratoderma and Congenital Alopecia 1 family:

Palmoplantar Keratoderma and Congenital Alopecia 2

Diseases related to Palmoplantar Keratoderma and Congenital Alopecia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Related Disease Score Top Affiliating Genes
1 hypotrichosis 30.9 GJB4 GJB3 GJB2 GJA1
2 keratosis 30.5 IVL GJB3 GJB2 GJA1
3 palmoplantar keratoderma and congenital alopecia 2 10.9
4 nail disorder, nonsyndromic congenital, 3 10.5
5 ainhum 10.4 GJB4 GJB2
6 alopecia, congenital 10.3
7 alopecia 10.3
8 hypotrichosis-deafness syndrome 10.3 GJB4 GJB3 GJB2
9 x-linked charcot-marie-tooth disease 10.2 GJB2 GJB1
10 deafness, autosomal dominant 2b 10.2 GJB3 GJB2
11 drug-induced hearing loss 10.2 GJB3 GJB2
12 deafness, autosomal recessive 91 10.2 GJB3 GJB2
13 1q21.1 recurrent microdeletion 10.2 GJA8 GJA5
14 deafness, autosomal dominant 2a 10.2 GJB3 GJB2
15 craniometaphyseal dysplasia, autosomal dominant 10.2 GJC1 GJA4 GJA1
16 deafness, autosomal dominant 9 10.2 GJB3 GJB2
17 palmoplantar keratosis 10.1 GJB4 GJB3 GJB2 GJA1
18 atrioventricular septal defect 10.1 GJC1 GJA5 GJA1
19 nonsyndromic hearing loss and deafness, dfna3 10.1 GJB6 GJB2
20 pelizaeus-merzbacher-like disease 10.1 GJC2 GJB1 GJA1
21 purulent labyrinthitis 10.1 GJB6 GJB2
22 labyrinthitis 10.1 GJB6 GJB2
23 viral labyrinthitis 10.1 GJB6 GJB2
24 syndactyly, type iii 10.1 GJC1 GJA1
25 congenital cytomegalovirus 10.1 GJB6 GJB2
26 spastic paraplegia 44, autosomal recessive 10.0 GJC2 GJB1
27 charcot-marie-tooth disease type x 10.0 GJC3 GJC2 GJB1
28 nonsyndromic hearing loss and deafness, dfnb1 10.0 GJB6 GJB3 GJB2
29 dfnb1 10.0 GJB6 GJB3 GJB2
30 keratitis-ichthyosis-deafness syndrome, autosomal dominant 10.0 GJB6 GJB2 GJA1
31 charcot-marie-tooth disease, x-linked dominant, 1 10.0 GJC3 GJC2 GJB1
32 deafness, autosomal dominant 3b 10.0 GJB6 GJB3 GJB2
33 deafness, autosomal recessive 1b 10.0 GJB6 GJB3 GJB2
34 vestibular disease 10.0 GJB6 GJB3 GJB2
35 x-linked nonsyndromic deafness 10.0 GJB6 GJB3 GJB2
36 deafness, x-linked 2 10.0 GJB6 GJB3 GJB2
37 hallermann-streiff syndrome 10.0 GJC2 GJC1 GJB1 GJA1
38 auditory system disease 10.0 GJB6 GJB3 GJB2
39 mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma 10.0 GJB4 GJB3
40 nevus, epidermal 10.0 IVL GJB4 GJB3 GJB2
41 inner ear disease 10.0 GJB6 GJB3 GJB2
42 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.9 GJB6 GJB3 GJB2
43 autosomal dominant nonsyndromic deafness 9.9 GJB6 GJB3 GJB2
44 deafness, autosomal dominant 3a 9.9 GJB6 GJB4 GJB3 GJB2
45 atrial standstill 9.9 SCN5A GJA5
46 deafness, autosomal recessive 1a 9.9 GJB6 GJB4 GJB3 GJB2
47 balo concentric sclerosis 9.9 GJC3 GJC2 GJB6
48 myasthenic syndrome, congenital, 5 9.8 SCN5A GJA5 GJA1
49 progressive familial heart block, type ia 9.8 SCN5A GJA5
50 atrioventricular block 9.8 SCN5A GJA5 GJA1

Graphical network of the top 20 diseases related to Palmoplantar Keratoderma and Congenital Alopecia 1:



Diseases related to Palmoplantar Keratoderma and Congenital Alopecia 1

Symptoms & Phenotypes for Palmoplantar Keratoderma and Congenital Alopecia 1

Human phenotypes related to Palmoplantar Keratoderma and Congenital Alopecia 1:

58 31 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000982
2 palmoplantar hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000972
3 congenital alopecia totalis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005597
4 fingernail dysplasia 58 31 frequent (33%) Frequent (79-30%) HP:0100798
5 abnormality of skin pigmentation 31 very rare (1%) HP:0001000
6 alopecia 31 HP:0001596
7 nail dysplasia 31 HP:0002164
8 dystrophic fingernails 31 HP:0008391
9 brittle hair 31 HP:0002299
10 leukonychia 31 HP:0001820
11 keratosis pilaris 31 HP:0032152

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skin Nails Hair Skin:
palmoplantar keratosis
pigmentary changes on the shins (1 patient)
focal palmoplantar keratoderma on weight-bearing areas
transgradient palmoplantar keratoderma on dorsal hands and feet
hyperkeratosis of perianal areas, auricles, knuckles, knees, and ankles
more
Skin Nails Hair Nails:
leukonychia totalis
dystrophic nails, mild

Skin Nails Hair Skin Histology:
orthohyperkeratosis
follicular plugging
perivascular lymphocytic infiltration in papillary dermis

Skin Nails Hair Hair:
alopecia, congenital
sparse, short, brittle hair on scalp
scant body hair
multiple pits on electron microscopy
cuticular weathering on electron microscopy

Clinical features from OMIM®:

104100 (Updated 05-Mar-2021)

GenomeRNAi Phenotypes related to Palmoplantar Keratoderma and Congenital Alopecia 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.62 GJB1
2 Decreased viability GR00055-A-2 9.62 GJB1
3 Decreased viability GR00240-S-1 9.62 GJA1
4 Decreased viability GR00249-S 9.62 GJA5 GJB1 IVL SP1
5 Decreased viability GR00381-A-1 9.62 ENTPD2
6 Decreased viability GR00386-A-1 9.62 GJA8 GJB4 GJB5 GJB6 GJC3 IVL
7 Decreased viability GR00402-S-2 9.62 ENTPD2 GJA4 GJB1 GJB2 SCN5A SP1

MGI Mouse Phenotypes related to Palmoplantar Keratoderma and Congenital Alopecia 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.06 GJA1 GJA4 GJA5 GJA8 GJB2 GJB3
2 embryo MP:0005380 9.86 GJA1 GJA8 GJB2 GJB3 GJB5 GJC1
3 nervous system MP:0003631 9.85 ENTPD2 GJA1 GJB1 GJB2 GJB6 GJC1
4 no phenotypic analysis MP:0003012 9.5 GJA1 GJA5 GJB2 GJB3 GJB6 GJC1
5 vision/eye MP:0005391 9.28 GJA1 GJA8 GJB1 GJB2 GJC1 GJC2

Drugs & Therapeutics for Palmoplantar Keratoderma and Congenital Alopecia 1

Search Clinical Trials , NIH Clinical Center for Palmoplantar Keratoderma and Congenital Alopecia 1

Cochrane evidence based reviews: alopecia congenita keratosis palmoplantaris

Genetic Tests for Palmoplantar Keratoderma and Congenital Alopecia 1

Anatomical Context for Palmoplantar Keratoderma and Congenital Alopecia 1

MalaCards organs/tissues related to Palmoplantar Keratoderma and Congenital Alopecia 1:

40
Skin

Publications for Palmoplantar Keratoderma and Congenital Alopecia 1

Articles related to Palmoplantar Keratoderma and Congenital Alopecia 1:

# Title Authors PMID Year
1
Exome sequencing reveals mutation in GJA1 as a cause of keratoderma-hypotrichosis-leukonychia totalis syndrome. 57 6
25168385 2015
2
Palmoplantar keratoderma, pseudo-ainhum, and universal atrichia: A new patient and review of the palmoplantar keratoderma-congenital alopecia syndrome. 57
20635335 2010
3
Keratoderma, hypotrichosis and leukonychia totalis: a new syndrome? 57
7577599 1995
4
Possible second case of tricho-oculo-dermo-vertebral (Alves) syndrome. 57
8488878 1993
5
Alopecia congenita: the incomplete dominant form of inheritance with varying expressivity. 57
13834517 1959
6
Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease. 61
31817921 2019
7
Connexin43 mutations linked to skin disease have augmented hemichannel activity. 61
30631135 2019

Variations for Palmoplantar Keratoderma and Congenital Alopecia 1

ClinVar genetic disease variations for Palmoplantar Keratoderma and Congenital Alopecia 1:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GJA1 NM_000165.5(GJA1):c.23G>T (p.Gly8Val) SNV Pathogenic 203467 rs864309644 6:121768016-121768016 6:121446870-121446870

UniProtKB/Swiss-Prot genetic disease variations for Palmoplantar Keratoderma and Congenital Alopecia 1:

73
# Symbol AA change Variation ID SNP ID
1 GJA1 p.Gly8Val VAR_075754 rs864309644

Expression for Palmoplantar Keratoderma and Congenital Alopecia 1

Search GEO for disease gene expression data for Palmoplantar Keratoderma and Congenital Alopecia 1.

Pathways for Palmoplantar Keratoderma and Congenital Alopecia 1

Pathways related to Palmoplantar Keratoderma and Congenital Alopecia 1 according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.24 GJD2 GJC2 GJC1 GJB6 GJB5 GJB4
2
Show member pathways
12.4 SP1 SCN5A IVL GJD2 GJC2 GJC1
3
Show member pathways
12.32 GJD2 GJC1 GJB3 GJB2 GJB1 GJA8
4
Show member pathways
12.29 SP1 GJD2 GJC2 GJC1 GJB6 GJB5
5
Show member pathways
11.96 GJD2 GJC2 GJC1 GJB6 GJB5 GJB4
6 11.9 SP1 SCN5A GJA1
7 11.64 SP1 IVL GJA1
8 11.38 SCN5A GJA5 GJA1
9 11.14 SP1 IVL GJA1
10 11.09 GJA5 GJA4 GJA1
11
Show member pathways
10.5 GJB2 GJB1 GJA1
12
Show member pathways
10.48 GJD2 GJC1

GO Terms for Palmoplantar Keratoderma and Congenital Alopecia 1

Cellular components related to Palmoplantar Keratoderma and Congenital Alopecia 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.31 SCN5A GJD2 GJC3 GJC2 GJC1 GJB6
2 integral component of membrane GO:0016021 10.22 SCN5A GJD2 GJC3 GJC2 GJC1 GJB6
3 plasma membrane GO:0005886 10.16 SCN5A GJD2 GJC3 GJC2 GJC1 GJB6
4 cell junction GO:0030054 10 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5
5 connexin complex GO:0005922 9.8 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5
6 intercalated disc GO:0014704 9.67 SCN5A GJC1 GJA5 GJA1
7 lateral plasma membrane GO:0016328 9.61 SCN5A GJB2 GJB1
8 gap junction GO:0005921 9.47 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5

Biological processes related to Palmoplantar Keratoderma and Congenital Alopecia 1 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 cell-cell signaling GO:0007267 10 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5
2 cell communication GO:0007154 9.8 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5
3 gap junction assembly GO:0016264 9.73 GJC1 GJB6 GJB2 GJB1 GJA5 GJA1
4 cell communication by electrical coupling GO:0010644 9.72 GJC2 GJB6 GJB2 GJA5 GJA1
5 gap junction-mediated intercellular transport GO:1990349 9.71 GJB6 GJB4 GJB2 GJA8
6 epididymis development GO:1905867 9.67 GJB5 GJB2 GJB1 GJA1
7 atrial cardiac muscle cell action potential GO:0086014 9.65 SCN5A GJC1 GJA1
8 endothelium development GO:0003158 9.63 GJA5 GJA4 GJA1
9 AV node cell to bundle of His cell communication by electrical coupling GO:0086053 9.61 GJC3 GJC1 GJA5
10 decidualization GO:0046697 9.57 GJB2 GJA1
11 positive regulation of blood vessel diameter GO:0097755 9.56 GJA5 GJA1
12 cell communication by electrical coupling involved in cardiac conduction GO:0086064 9.55 GJA5 GJA1
13 regulation of atrial cardiac muscle cell membrane depolarization GO:0060371 9.54 SCN5A GJA5
14 regulation of cell communication by electrical coupling GO:0010649 9.52 GJA5 GJA1
15 SA node cell to atrial cardiac muscle cell communication by electrical coupling GO:0086021 9.51 GJC1 GJA5
16 transmembrane transport GO:0055085 9.5 SCN5A GJD2 GJC3 GJC2 GJC1 GJB6
17 positive regulation of cell communication by chemical coupling GO:0010652 9.49 GJA5 GJA1

Molecular functions related to Palmoplantar Keratoderma and Congenital Alopecia 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction channel activity GO:0005243 9.47 GJD2 GJC3 GJC2 GJC1 GJB6 GJB5
2 connexin binding GO:0071253 9.4 GJA5 GJA1
3 gap junction hemi-channel activity GO:0055077 9.37 GJA5 GJA1
4 gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling GO:0086077 9.33 GJC3 GJC1 GJA5
5 gap junction channel activity involved in cardiac conduction electrical coupling GO:0086075 9.32 GJA5 GJA1
6 gap junction channel activity involved in SA node cell-atrial cardiac muscle cell electrical coupling GO:0086020 9.26 GJC1 GJA5
7 gap junction channel activity involved in cell communication by electrical coupling GO:1903763 9.26 GJC2 GJB6 GJB2 GJA1

Sources for Palmoplantar Keratoderma and Congenital Alopecia 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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