PPKCA1
MCID: PLM158
MIFTS: 37

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 56 12 73 15
Autosomal Dominant Palmoplantar Hyperkeratosis and Congenital Alopecia 12 52 58
Autosomal Dominant Palmoplantar Keratoderma and Congenital Alopecia 12 52 58
Palmoplantar Keratoderma and Congenital Alopecia, Stevanovic Type 12 52 58
Keratoderma-Hypotrichosis-Leukonychia Totalis Syndrome 56 12 73
Ppk-Ca, Stevanovic Type 12 52 58
Ppkca1 56 12 73
Ppkca, Stevanovic Type 56 73
Alopecia Congenita with Hyperkeratosis of the Palms and Soles 52
Keratoderma, Palmoplantar, with Congenital Alopecia, Type 1 39
Palmoplantar Keratoderma with Congenital Alopecia 56
Alopecia Congenita Keratosis Palmoplantaris 43
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:

56
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 56 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

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1010 Definition A rare genetic skin disorder characterized by absence of scalp and body hair and palmoplantar keratoderma, without other hand complications. Epidemiology To date, ten individuals with a clinical diagnosis of autosomal dominant palmoplantar keratoderma and congenital alopecia (PPK-CA) have been reported. Clinical description Autosomal 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). Etiology The genetic basis of autosomal dominant PPK-CA is unknown. Transmission appears to be autosomal dominant. Genetic counseling Transmission 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 keratosis and hypotrichosis. 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 : 56 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)

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 2 family:

Palmoplantar Keratoderma and Congenital Alopecia 1

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

(show all 47)
# Related Disease Score Top Affiliating Genes
1 keratosis 30.7 GJB2 GJA1
2 hypotrichosis 29.5 GJB4 GJB3 GJB2 GJA1
3 palmoplantar keratoderma and congenital alopecia 2 11.3
4 nail disorder, nonsyndromic congenital, 3 10.7
5 alopecia, congenital 10.5
6 alopecia 10.5
7 leukodystrophy, hypomyelinating, 2 9.9 GJB4 GJA1
8 keratitis-ichthyosis-deafness syndrome, autosomal dominant 9.9 GJB2 GJA1
9 deafness, autosomal recessive 9.7 GJB3 GJB2
10 nonsyndromic hearing loss and deafness, dfnb1 9.7 GJB3 GJB2
11 nonsyndromic hearing loss 9.7 GJB3 GJB2
12 dfnb1 9.7 GJB3 GJB2
13 deafness, autosomal dominant 2b 9.6 GJB3 GJB2
14 deafness, autosomal dominant 3b 9.6 GJB3 GJB2
15 drug-induced hearing loss 9.6 GJB3 GJB2
16 deafness, autosomal recessive 91 9.6 GJB3 GJB2
17 deafness, autosomal dominant 2a 9.6 GJB3 GJB2
18 deafness, autosomal recessive 1b 9.6 GJB3 GJB2
19 deafness, autosomal dominant 9 9.6 GJB3 GJB2
20 x-linked nonsyndromic deafness 9.6 GJB3 GJB2
21 vestibular disease 9.5 GJB3 GJB2
22 deafness, x-linked 2 9.5 GJB3 GJB2
23 autosomal dominant non-syndromic sensorineural deafness type dfna 9.5 GJB3 GJB2
24 palmoplantar keratoderma, epidermolytic 9.5 GJB3 GJB2
25 auditory system disease 9.4 GJB3 GJB2
26 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.4 GJB3 GJB2
27 inner ear disease 9.3 GJB3 GJB2
28 autosomal recessive non-syndromic sensorineural deafness type dfnb 9.3 GJB3 GJB2 GJA1
29 hypotrichosis-deafness syndrome 9.3 GJB4 GJB3 GJB2
30 deafness, autosomal dominant 3a 9.3 GJB4 GJB3 GJB2
31 deafness, autosomal recessive 1a 9.3 GJB4 GJB3 GJB2
32 nevus, epidermal 9.3 GJB4 GJB3 GJB2
33 autosomal dominant nonsyndromic deafness 9.2 GJB3 GJB2
34 pseudoainhum 9.0 GJB4 GJB3 GJB2 GJA1
35 hereditary lymphedema ic 9.0 GJB4 GJB3 GJB2 GJA1
36 knuckle pads 9.0 GJB4 GJB3 GJB2 GJA1
37 keratoderma, palmoplantar, with deafness 9.0 GJB4 GJB3 GJB2 GJA1
38 clouston syndrome 9.0 GJB4 GJB3 GJB2 GJA1
39 oculodentodigital dysplasia 9.0 GJB4 GJB3 GJB2 GJA1
40 palmoplantar keratosis 9.0 GJB4 GJB3 GJB2 GJA1
41 ectodermal dysplasia 8.9 GJB4 GJB3 GJB2 GJA1
42 vohwinkel syndrome 8.9 GJB5 GJB4 GJB3 GJB2
43 skin disease 8.9 GJB4 GJB3 GJB2 GJA1
44 erythrokeratoderma 8.6 GJB5 GJB4 GJB3 GJB2 GJA1
45 bart-pumphrey syndrome 8.6 GJB5 GJB4 GJB3 GJB2 GJA1
46 erythrokeratodermia variabilis et progressiva 1 8.6 GJB5 GJB4 GJB3 GJB2 GJA1
47 charcot-marie-tooth disease 8.6 GJB5 GJB4 GJB3 GJB2 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:

56
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

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 embryo MP:0005380 9.26 GJA1 GJB2 GJB3 GJB5
2 hearing/vestibular/ear MP:0005377 8.8 GJA1 GJB2 GJB3

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. 6 56
25168385 2015
2
Palmoplantar keratoderma, pseudo-ainhum, and universal atrichia: A new patient and review of the palmoplantar keratoderma-congenital alopecia syndrome. 56
20635335 2010
3
Keratoderma, hypotrichosis and leukonychia totalis: a new syndrome? 56
7577599 1995
4
Possible second case of tricho-oculo-dermo-vertebral (Alves) syndrome. 56
8488878 1993
5
Alopecia congenita: the incomplete dominant form of inheritance with varying expressivity. 56
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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.76 GJB5 GJB4 GJB3 GJB2 GJA1
2
Show member pathways
12.42 GJB5 GJB4 GJB3 GJB2 GJA1
3
Show member pathways
11.95 GJB3 GJB2 GJA1
4
Show member pathways
11.84 GJB5 GJB4 GJB3 GJB2 GJA1
5
Show member pathways
11.01 GJB5 GJB4 GJB3 GJB2 GJA1
6
Show member pathways
10.28 GJB2 GJA1

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 integral component of membrane GO:0016021 9.72 GJB5 GJB4 GJB3 GJB2 GJA1
2 plasma membrane GO:0005886 9.65 GJB5 GJB4 GJB3 GJB2 GJA1
3 cell junction GO:0030054 9.55 GJB5 GJB4 GJB3 GJB2 GJA1
4 gap junction GO:0005921 9.35 GJB5 GJB4 GJB3 GJB2 GJA1
5 connexin complex GO:0005922 9.02 GJB5 GJB4 GJB3 GJB2 GJA1

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.65 GJB5 GJB4 GJB3 GJB2 GJA1
2 cell-cell signaling GO:0007267 9.55 GJB5 GJB4 GJB3 GJB2 GJA1
3 response to lipopolysaccharide GO:0032496 9.51 GJB2 GJA1
4 response to estradiol GO:0032355 9.49 GJB2 GJA1
5 response to ischemia GO:0002931 9.48 GJB2 GJA1
6 response to retinoic acid GO:0032526 9.46 GJB2 GJA1
7 decidualization GO:0046697 9.43 GJB2 GJA1
8 gap junction assembly GO:0016264 9.4 GJB2 GJA1
9 cell communication by electrical coupling GO:0010644 9.37 GJB2 GJA1
10 gap junction-mediated intercellular transport GO:1990349 9.32 GJB4 GJB2
11 epididymis development GO:1905867 9.13 GJB5 GJB2 GJA1
12 cell communication GO:0007154 9.02 GJB5 GJB4 GJB3 GJB2 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 9.02 GJB5 GJB4 GJB3 GJB2 GJA1
2 gap junction channel activity involved in cell communication by electrical coupling GO:1903763 8.96 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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