FPHH
MCID: HYP744
MIFTS: 38

Hyperpigmentation with or Without Hypopigmentation, Familial Progressive (FPHH)

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hyperpigmentation with or Without Hypopigmentation, Familial...

MalaCards integrated aliases for Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

Name: Hyperpigmentation with or Without Hypopigmentation, Familial Progressive 56 73
Familial Progressive Hyperpigmentation with or Without Hypopigmentation 12 29 6 15
Fphh 56 12 58 73
Melanosis Universalis Hereditaria 56 12 73
Muh 56 12 73
Hyperpigmentation, Familial Progressive, 2, Formerly; Fph2, Formerly 56
Hyperpigmentation, Familial Progressive, 2, Formerly 56
Hyperpigmentation with or Without Hypopigmentation 56
Familial Progressive Hyper- and Hypopigmentation 58
Hyperpigmentation, Familial Progressive 71
Melanosis Universalis Hereditaria; Muh 56
Fph2, Formerly 56

Characteristics:

Orphanet epidemiological data:

58
familial progressive hyper- and hypopigmentation
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset birth to early infancy
hyperpigmented patches increased in size and number with age


HPO:

31
hyperpigmentation with or without hypopigmentation, familial progressive:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0111373
OMIM 56 145250
ICD10 via Orphanet 33 L81.8
UMLS via Orphanet 72 C1840392
Orphanet 58 ORPHA280628
MedGen 41 C1840392
UMLS 71 C1840392

Summaries for Hyperpigmentation with or Without Hypopigmentation, Familial...

OMIM : 56 Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is characterized by diffuse hyperpigmentation of variable intensity sometimes associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules. These features, which involve the face, neck, trunk, and limbs, are seen at birth or develop early in infancy (summary by Wang et al., 2009 and Amyere et al., 2011). Also see familial progressive hyperpigmentation (FPH1; 614233). (145250)

MalaCards based summary : Hyperpigmentation with or Without Hypopigmentation, Familial Progressive, also known as familial progressive hyperpigmentation with or without hypopigmentation, is related to familial progressive hyperpigmentation and hyperpigmentation, familial progressive, 1. An important gene associated with Hyperpigmentation with or Without Hypopigmentation, Familial Progressive is KITLG (KIT Ligand), and among its related pathways/superpathways are Hematopoietic Stem Cells and Lineage-specific Markers and Fc-GammaR Pathway. Affiliated tissues include skin, and related phenotypes are vitiligo and hyperkeratosis

Disease Ontology : 12 A skin disease characterized by progressive, diffuse hyperpigmentation of variable intensity sometimes associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules that has material basis in heterozygous mutation in KITLG on chromosome 12q21.32.

UniProtKB/Swiss-Prot : 73 Hyperpigmentation with or without hypopigmentation, familial progressive: A disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age. Hyperpigmentation has variable intensity, and sometimes is associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules.

Related Diseases for Hyperpigmentation with or Without Hypopigmentation, Familial...

Diseases related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 familial progressive hyperpigmentation 11.7
2 hyperpigmentation, familial progressive, 1 11.3
3 anemia, x-linked, with or without neutropenia and/or platelet abnormalities 11.2
4 sickle cell anemia 11.2
5 neisseria meningitidis infection 11.2
6 mu chain disease 10.4 VPREB1 IGLL1
7 bird fancier's lung 10.3 IGLL1 CD79A
8 lambda 5 deficiency 10.3 VPREB1 IGLL1 CD79B
9 monoclonal paraproteinemia 10.3 IGHV4-38-2 CD79A
10 retina lymphoma 10.2 IGLL5 IGHV4-38-2
11 agammaglobulinemia, non-bruton type 10.2 IGLL1 CD79B CD79A
12 mental retardation, x-linked, syndromic, wu type 10.2 SMAD9 CACNA1E
13 dowling-degos disease 1 10.2
14 pediatric lymphoma 10.2 IGHV4-38-2 CD79A
15 composite lymphoma 10.1 IGHV4-38-2 CD79A
16 testicular lymphoma 10.1 IGHV4-38-2 CD79B CD79A
17 waldenstroem's macroglobulinemia 10.1 IGHV4-38-2 CD79B CD79A
18 agammaglobulinemia 10.1 VPREB1 IGLL1 CD79B CD79A
19 spleen cancer 10.1 IGHV4-38-2 CD79B CD79A
20 cll/sll 10.1 IGHV4-38-2 CD79B CD79A
21 46,xy sex reversal 9 10.1 SMAD9 CACNA1E
22 central nervous system hematologic cancer 10.1 IGHV4-38-2 CD79B CD79A
23 failure of tooth eruption, primary 10.1 SPAG17 AP4M1
24 marginal zone b-cell lymphoma 10.1 IGHV4-38-2 CD79B CD79A
25 lentigines 10.1
26 legius syndrome 10.1
27 dyschromatosis universalis hereditaria 2 10.1
28 dyschromatosis universalis hereditaria 10.1
29 pigmentation disease 10.1
30 erythrokeratoderma ''en cocardes'' 10.1
31 rare genetic skin disease 10.1
32 thyroid carcinoma 10.1
33 plasma cell neoplasm 10.1 IGLL5 IGHV4-38-2 CD79A
34 schuurs-hoeijmakers syndrome 10.0 IGLL5 IGHV4-38-2
35 indolent systemic mastocytosis 10.0 VPREB1 KITLG
36 mature b-cell neoplasm 10.0 IGLL5 IGHV4-38-2 CD79A
37 lymphoma, mucosa-associated lymphoid type 10.0 IGHV4-38-2 CD79B CD79A

Graphical network of the top 20 diseases related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:



Diseases related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive

Symptoms & Phenotypes for Hyperpigmentation with or Without Hypopigmentation, Familial...

Human phenotypes related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 vitiligo 31 occasional (7.5%) HP:0001045
2 hyperkeratosis 31 HP:0000962
3 hypopigmented skin patches 31 HP:0001053
4 multiple lentigines 31 HP:0001003
5 cafe-au-lait spot 31 HP:0000957
6 progressive hyperpigmentation 31 HP:0007505

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
hypopigmented skin patches
cafe-au-lait spots
familial progressive hyperpigmentation and hypopigmentation
hyperpigmented skin patches (face, neck, trunk, limbs, lip, oral mucosa, palms, and soles)
lentiginosis, generalized (in some patients)
more
Skin Nails Hair Skin Histology:
hyperkeratosis with increased melanin in epidermis, especially basal cell layer and tips of rete ridges

Clinical features from OMIM:

145250

GenomeRNAi Phenotypes related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.32 KITLG
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-130 9.32 MAP3K12
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-141 9.32 NME3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 9.32 MAP3K12
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.32 MAP3K12
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.32 NME3
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-41 9.32 KITLG
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-47 9.32 NME3
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-88 9.32 NME3
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-9 9.32 NME3
11 Decreased replication of vaccinia virus (VACV) GR00362-A 8.65 ERH

Drugs & Therapeutics for Hyperpigmentation with or Without Hypopigmentation, Familial...

Search Clinical Trials , NIH Clinical Center for Hyperpigmentation with or Without Hypopigmentation, Familial Progressive

Genetic Tests for Hyperpigmentation with or Without Hypopigmentation, Familial...

Genetic tests related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

# Genetic test Affiliating Genes
1 Familial Progressive Hyperpigmentation with or Without Hypopigmentation 29 KITLG

Anatomical Context for Hyperpigmentation with or Without Hypopigmentation, Familial...

MalaCards organs/tissues related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

40
Skin

Publications for Hyperpigmentation with or Without Hypopigmentation, Familial...

Articles related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

(show all 13)
# Title Authors PMID Year
1
KITLG mutations cause familial progressive hyper- and hypopigmentation. 61 56 6
21368769 2011
2
Gain-of-function mutation of KIT ligand on melanin synthesis causes familial progressive hyperpigmentation. 56 6
19375057 2009
3
Familial hyper- and hypopigmentation with age-related pattern change. 56 6
15551335 2005
4
Progressive hyperpigmentation and generalized lentiginosis without associated systemic symptoms: a rare hereditary pigmentation disorder in south-east Germany. 6 56
15040480 2004
5
Universal inherited melanodyschromatosis: a case of melanosis universalis hereditaria? 56
2802660 1989
6
Hereditary congenital hypopigmented and hyperpigmented macules. 56
666331 1978
7
Familial progressive hyperpigmentation. 56
4326548 1971
8
Diffuse pigmentation in brothers. 56
14371572 1955
9
Novel mutation in the KITLG gene in familial progressive hyperpigmentation with or without hypopigmentation. 61
32189379 2020
10
Electrochemical Mechanism and Effect of Carbon Nanotubes on the Electrochemical Performance of Fe1.19(PO4)(OH)0.57(H2O)0.43 Cathode Material for Li-Ion Batteries. 61
30216721 2018
11
Familial progressive hyper- and hypopigmentation: a report on a Chinese family and evidence for genetic heterogeneity. 61
29186243 2017
12
Familial progressive hyper- and hypopigmentation and malignancy in two families with new mutations in KITLG. 61
26179221 2015
13
Familial progressive hypo- and hyperpigmentation: a variant case. 61
22565436 2012

Variations for Hyperpigmentation with or Without Hypopigmentation, Familial...

ClinVar genetic disease variations for Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KITLG NM_000899.5(KITLG):c.107A>G (p.Asn36Ser)SNV Pathogenic 12813 rs121918653 12:88939551-88939551 12:88545774-88545774
2 KITLG NM_000899.5(KITLG):c.98T>C (p.Val33Ala)SNV Pathogenic 183168 rs730882156 12:88939560-88939560 12:88545783-88545783
3 KITLG NM_000899.5(KITLG):c.100A>C (p.Thr34Pro)SNV Pathogenic 183169 rs730882157 12:88939558-88939558 12:88545781-88545781

UniProtKB/Swiss-Prot genetic disease variations for Hyperpigmentation with or Without Hypopigmentation, Familial Progressive:

73
# Symbol AA change Variation ID SNP ID
1 KITLG p.Asn36Ser VAR_063237 rs121918653

Expression for Hyperpigmentation with or Without Hypopigmentation, Familial...

Search GEO for disease gene expression data for Hyperpigmentation with or Without Hypopigmentation, Familial Progressive.

Pathways for Hyperpigmentation with or Without Hypopigmentation, Familial...

Pathways related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.2 KITLG CD79B CD79A
2
Show member pathways
11.04 RHOH CD79B CD79A CACNA1E

GO Terms for Hyperpigmentation with or Without Hypopigmentation, Familial...

Cellular components related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 external side of plasma membrane GO:0009897 9.35 IGLL5 IGLL1 IGHV4-38-2 CD79B CD79A
2 immunoglobulin complex, circulating GO:0042571 9.33 IGLL5 IGLL1 IGHV4-38-2
3 B cell receptor complex GO:0019815 8.62 CD79B CD79A

Biological processes related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 complement activation, classical pathway GO:0006958 9.5 IGLL5 IGLL1 IGHV4-38-2
2 phagocytosis, engulfment GO:0006911 9.43 IGLL5 IGLL1 IGHV4-38-2
3 positive regulation of B cell activation GO:0050871 9.33 IGLL5 IGLL1 IGHV4-38-2
4 phagocytosis, recognition GO:0006910 9.13 IGLL5 IGLL1 IGHV4-38-2
5 B cell receptor signaling pathway GO:0050853 9.02 IGLL5 IGLL1 IGHV4-38-2 CD79B CD79A

Molecular functions related to Hyperpigmentation with or Without Hypopigmentation, Familial Progressive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 antigen binding GO:0003823 9.13 IGLL5 IGLL1 IGHV4-38-2
2 immunoglobulin receptor binding GO:0034987 8.8 IGLL5 IGLL1 IGHV4-38-2

Sources for Hyperpigmentation with or Without Hypopigmentation, Familial...

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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