PKKSCC
MCID: PLM173
MIFTS: 34

Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal (PKKSCC)

Categories: Cancer diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

MalaCards integrated aliases for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

Name: Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal 57 29 6
Palmoplantar Hyperkeratosis and True Hermaphroditism 57 29 13 6
Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and Sex Reversal 57 72 36
Palmoplantar Hyperkeratosis-Xx Sex Reversal-Predisposition to Squamous Cell Carcinoma Syndrome 58
Palmoplantar Keratoderma-Xx Sex Reversal-Predisposition to Squamous Cell Carcinoma Syndrome 58
Keratoderma, Palmoplantar, with Squamous Cell Carcinoma of Skin and Sex Reversal 72
Pkkscc 72

Characteristics:

Orphanet epidemiological data:

58
palmoplantar keratoderma-xx sex reversal-predisposition to squamous cell carcinoma syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
one consanguineous italian family and 1 unrelated patient have been reported (last curated november 2016)


HPO:

31
palmoplantar hyperkeratosis with squamous cell carcinoma of skin and 46,xx sex reversal:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare gynaecological and obstetric diseases
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

KEGG : 36 Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal (PPK-SCC) is a form of 46,XX disorder of sex development. It is a rare autosomal recessive disorder caused due to biallelic loss of function mutations in RSPO1 gene. RSPO1 is one of the most important genes controlling female gonadal differentiation.

MalaCards based summary : Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal, is also known as palmoplantar hyperkeratosis and true hermaphroditism. An important gene associated with Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal is RSPO1 (R-Spondin 1), and among its related pathways/superpathways is Wnt signaling pathway. Affiliated tissues include skin, and related phenotypes are palmoplantar keratoderma and squamous cell carcinoma of the skin

UniProtKB/Swiss-Prot : 72 Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal: A recessive syndrome characterized by XX (female to male) SRY- independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin.

More information from OMIM: 610644

Related Diseases for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Symptoms & Phenotypes for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Human phenotypes related to Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000982
2 squamous cell carcinoma of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0006739
3 sex reversal 58 31 hallmark (90%) Very frequent (99-80%) HP:0012245
4 hypertriglyceridemia 31 HP:0002155
5 hypercholesterolemia 31 HP:0003124
6 hypospadias 31 HP:0000047
7 gynecomastia 31 HP:0000771
8 decreased testicular size 31 HP:0008734
9 nail dystrophy 31 HP:0008404
10 laryngeal carcinoma 31 HP:0012118
11 small nail 31 HP:0001792
12 sclerodactyly 31 HP:0011838
13 clitoral hypertrophy 31 HP:0008665
14 ovotestis 31 HP:0012861
15 palmoplantar hyperhidrosis 31 HP:0007410
16 orthokeratotic hyperkeratosis 31 HP:0025080
17 premature loss of permanent teeth 31 HP:0006357
18 carcinoma 31 HP:0030731

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Laboratory Abnormalities:
hypertriglyceridemia
hypercholesterolemia

Neoplasia:
laryngeal carcinoma
multiple squamous cell carcinomas in areas of hyperkeratotic skin
pulmonary metastases of squamous cell carcinoma

Head And Neck Teeth:
premature loss of permanent teeth
chronic periodontal disease

Genitourinary External Genitalia Female:
clitoral enlargement
ambiguous external genitalia

Genitourinary External Genitalia Male:
severe hypogenitalism (in 46,xx males)
hypospadias (in 46,xx males)

Genitourinary Internal Genitalia Female:
ovotestis (in 46,xx female)
seminiferous tubules surrounded by ovarian-type stroma (in 46,xx female)
seminoma infiltrating stroma (in 46,xx female)

Skin Nails Hair Skin:
palmoplantar keratoderma
sclerodactyly
hyperhidrosis of palms and soles
squamous cell carcinomas in areas of hyperkeratosis

Skin Nails Hair Skin Histology:
orthokeratotic hyperkeratosis
moderately differentiated squamous cell carcinoma

Skin Nails Hair Nails:
dystrophic nails
nail hypoplasia
longitudinal ridging of nails

Chest Breasts:
gynecomastia (in 46,xx males)

Genitourinary Internal Genitalia Male:
testicular hypoplasia (in 46,xx males)
nodular hyperplasia of leydig cells (in 46,xx males)
seminoma (right groin mass in 46,xx female)

Endocrine Features:
hypogenitalism (in 46,xx males)
low plasma testosterone levels (in 46,xx males)
high plasma follicle-stimulating hormone (fsh) levels (in 46,xx males)

Clinical features from OMIM®:

610644 (Updated 05-Apr-2021)

Drugs & Therapeutics for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Search Clinical Trials , NIH Clinical Center for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal

Genetic Tests for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Genetic tests related to Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

# Genetic test Affiliating Genes
1 Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal 29 RSPO1
2 Palmoplantar Hyperkeratosis and True Hermaphroditism 29

Anatomical Context for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

MalaCards organs/tissues related to Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

40
Skin

Publications for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Articles related to Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

# Title Authors PMID Year
1
Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. 57 6
18085567 2008
2
R-spondin1 is essential in sex determination, skin differentiation and malignancy. 6 57
17041600 2006
3
XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family. 6 57
16158431 2005
4
R-spondin1 tips the balance in sex determination. 57
17072299 2006
5
Association of palmoplantar keratoderma, cutaneous squamous cell carcinoma, dental anomalies, and hypogenitalism in four siblings with 46,XX karyotype: a new syndrome. 57
16227098 2005
6
Huriez syndrome: association with squamous cell carcinoma and a surgical approach. 57
16079734 2005
7
Huriez syndrome: case report with a detailed analysis of skin dendritic cells. 57
11069529 2000
8
An SRY-negative XX male with Huriez syndrome. 57
10733237 2000
9
A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. 57
8475082 1993
10
Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with palmoplantar keratoderma: A review of literature and expansion of clinical phenotype. 61
29575617 2018

Variations for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

ClinVar genetic disease variations for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RSPO1 RSPO1, 1-BP INS, 896G Insertion Pathogenic 1603 GRCh37:
GRCh38:
2 RSPO1 RSPO1, EX4 DEL Deletion Pathogenic 1604 GRCh37:
GRCh38:
3 RSPO1 NM_001242908.2(RSPO1):c.286+1G>A SNV Pathogenic 1605 rs1570099690 GRCh37: 1:38082155-38082155
GRCh38: 1:37616483-37616483
4 RSPO1 NM_001242908.2(RSPO1):c.315C>A (p.Cys105Ter) SNV Pathogenic 1034391 GRCh37: 1:38079977-38079977
GRCh38: 1:37614305-37614305

Cosmic variations for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal:

9 (show top 50) (show all 15557)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM108405939 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.316C>T p.P106S 16:31064213-31064213 15
2 COSM131595377 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.947C>T p.S316L 16:31062050-31062050 15
3 COSM101742625 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.878C>T p.S293L 16:31062050-31062050 15
4 COSM131595368 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1886C>T p.P629L 16:31061111-31061111 15
5 COSM87498632 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.247C>T p.P83S 16:31064213-31064213 15
6 COSM101742795 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.247C>T p.P83S 16:31064213-31064213 15
7 COSM133260761 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.878C>T p.S293L 16:31062050-31062050 15
8 COSM132355968 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1817C>T p.P606L 16:31061111-31061111 15
9 COSM132355981 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.878C>T p.S293L 16:31062050-31062050 15
10 COSM131595526 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.316C>T p.P106S 16:31064213-31064213 15
11 COSM87498178 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1817C>T p.P606L 16:31061111-31061111 15
12 COSM101742614 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1817C>T p.P606L 16:31061111-31061111 15
13 COSM133260750 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1817C>T p.P606L 16:31061111-31061111 15
14 COSM133260941 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.247C>T p.P83S 16:31064213-31064213 15
15 COSM108405783 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.1886C>T p.P629L 16:31061111-31061111 15
16 COSM108405799 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.947C>T p.S316L 16:31062050-31062050 15
17 COSM132356152 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.247C>T p.P83S 16:31064213-31064213 15
18 COSM87498195 ZNF668 skin,NS,carcinoma,squamous cell carcinoma c.878C>T p.S293L 16:31062050-31062050 15
19 COSM101590418 ZMYM2 skin,NS,carcinoma,squamous cell carcinoma c.946C>T p.Q316* 13:20002948-20002948 15
20 COSM143109510 ZMYM2 skin,NS,carcinoma,squamous cell carcinoma c.946C>T p.Q316* 13:20002948-20002948 15
21 COSM101612017 ZMYM2 skin,NS,carcinoma,squamous cell carcinoma c.946C>T p.Q316* 13:20002948-20002948 15
22 COSM107139107 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.683A>C p.K228T 3:147395971-147395971 15
23 COSM101870708 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.522C>T p.F174= 3:147396018-147396018 15
24 COSM129142467 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.672C>T p.F224= 3:147396018-147396018 15
25 COSM118697764 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.71-4725A>C p.? 3:147395971-147395971 15
26 COSM115494047 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.569A>C p.K190T 3:147395971-147395971 15
27 COSM118700792 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.71-4772C>T p.? 3:147396018-147396018 15
28 COSM115497576 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.282C>G p.A94= 3:147396258-147396258 15
29 COSM129137619 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.135G>A p.K45= 3:147403964-147403964 15
30 COSM129143394 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.1026G>C p.P342= 3:147391059-147391059 15
31 COSM115492982 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.-15-1152G>A p.? 3:147403964-147403964 15
32 COSM107143716 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.396C>G p.A132= 3:147396258-147396258 15
33 COSM129143406 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.432C>G p.A144= 3:147396258-147396258 15
34 COSM101872056 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.282C>G p.A94= 3:147396258-147396258 15
35 COSM120258678 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.-16G>A p.? 3:147403964-147403964 15
36 COSM101866693 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.569A>C p.K190T 3:147395971-147395971 15
37 COSM101864973 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.-15-1152G>A p.? 3:147403964-147403964 15
38 COSM115497565 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.876G>C p.P292= 3:147391059-147391059 15
39 COSM120264120 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.876G>C p.P292= 3:147391059-147391059 15
40 COSM107142798 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.636C>T p.F212= 3:147396018-147396018 15
41 COSM101867690 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.314T>G p.V105G 3:147396226-147396226 15
42 COSM120260940 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.314T>G p.V105G 3:147396226-147396226 15
43 COSM118702064 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.71-5012C>G p.? 3:147396258-147396258 15
44 COSM129140070 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.464T>G p.V155G 3:147396226-147396226 15
45 COSM120260164 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.569A>C p.K190T 3:147395971-147395971 15
46 COSM118698551 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.71-4980T>G p.? 3:147396226-147396226 15
47 COSM101872044 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.876G>C p.P292= 3:147391059-147391059 15
48 COSM118702056 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.258G>C p.P86= 3:147391059-147391059 15
49 COSM129139322 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.719A>C p.K240T 3:147395971-147395971 15
50 COSM107143709 ZIC4 skin,NS,carcinoma,squamous cell carcinoma c.990G>C p.P330= 3:147391059-147391059 15

Expression for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Search GEO for disease gene expression data for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal.

Pathways for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Pathways related to Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin and 46,xx Sex Reversal according to KEGG:

36
# Name Kegg Source Accession
1 Wnt signaling pathway hsa04310

GO Terms for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

Sources for Palmoplantar Hyperkeratosis with Squamous Cell Carcinoma of Skin...

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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