NDNC4
MCID: NLD014
MIFTS: 40

Nail Disorder, Nonsyndromic Congenital, 4 (NDNC4)

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

Aliases & Classifications for Nail Disorder, Nonsyndromic Congenital, 4

MalaCards integrated aliases for Nail Disorder, Nonsyndromic Congenital, 4:

Name: Nail Disorder, Nonsyndromic Congenital, 4 57 70
Anonychia Congenita 57 12 20 43 36 13 44
Anonychia 43 29 6 32
Hyponychia Congenita 12 43 72
Nonsyndromic Congenital Nail Disorder 4 12 15
Anonychia/hyponychia Congenita 57 72
Isolated Congenital Anonychia 20 58
Anonychia Congenita Totalis 58 72
Ndnc4 57 72
Autosomal Recessive Nonsyndromic Congenital Nail Disorder-4 20
Nail Disorder, Nonsyndromic, Congenital, Type 4 39
Nail Disorder, Non-Syndromic Congenital, 4 72
Nonsyndromic Congenital Nail Disorder, 4 20
Congenital Absence of Nails 43
Congenital Anonychia 20
Isolated Anonychia 58
Anonychia Totalis 57
Aplastic Nails 43
Absent Nails 43

Characteristics:

Orphanet epidemiological data:

58
isolated congenital anonychia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);
anonychia congenita totalis
Inheritance: Autosomal recessive;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
patients have no abnormalities of hair, teeth, or bone


HPO:

31
nail disorder, nonsyndromic congenital, 4:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0080082
OMIM® 57 206800
OMIM Phenotypic Series 57 PS161050
KEGG 36 H00683
ICD10 32 Q84.3
ICD10 via Orphanet 33 Q84.3
UMLS via Orphanet 71 C0265998
SNOMED-CT via HPO 68 23610003 258211005
UMLS 70 C3277900

Summaries for Nail Disorder, Nonsyndromic Congenital, 4

OMIM® : 57 Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050). (206800) (Updated 20-May-2021)

MalaCards based summary : Nail Disorder, Nonsyndromic Congenital, 4, also known as anonychia congenita, is related to nail disorder, nonsyndromic congenital, 9 and epidermolysis bullosa. An important gene associated with Nail Disorder, Nonsyndromic Congenital, 4 is RSPO4 (R-Spondin 4), and among its related pathways/superpathways are mTOR signaling pathway (KEGG) and Wnt signaling pathway. Affiliated tissues include bone, breast and skin, and related phenotypes are anonychia and Decreased shRNA abundance (Z-score < -2)

Disease Ontology : 12 A nonsyndromic congenital nail disorder that is characterized by complete absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies, and that has material basis in homozygous or compound heterozygous mutation in the R-spondin-4 gene on chromosome 20p13.

MedlinePlus Genetics : 43 Anonychia congenita is a condition that affects the fingernails and toenails. Individuals with this condition are typically missing all of their fingernails and toenails (anonychia). This absence of nails is noticeable from birth (congenital). In some cases, only part of the nail is missing (hyponychia) or not all fingers and toes are affected. All of the other tissues at the tips of the fingers and toes, including structures that usually support the nail and its growth (such as the nail bed), are normal.Individuals with anonychia congenita do not have any other health problems related to the condition.

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79143 Definition Isolated congenital anonychia is characterized by nail abnormalities ranging from onychodystrophy (dystrophic nails) to anonychia (absence of nails). Onychodystrophy-anonychia has been described in at least four generations of a family with male-to-male transmission, suggesting autosomal dominant transmission. Anonychia has been described in approximately less than 20 cases; it is likely to be transmitted as an autosomal recessive trait. Total anonychia congenita, in which all the fingernails and toenails are absent, may have an autosomal dominant inheritance pattern.

KEGG : 36 Nonsyndromic anonychia is a condition in which the nails of the fingers and toes are congenitally absent without significant bone anomalies. The teeth and hair are normal. Mutation in RSPO4, a Wnt-signaling component, has been identified.

UniProtKB/Swiss-Prot : 72 Nail disorder, non-syndromic congenital, 4: A nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies.

Related Diseases for Nail Disorder, Nonsyndromic Congenital, 4

Diseases in the Nail Disease family:

Nail Disorder, Nonsyndromic Congenital, 6 Nail Disorder, Nonsyndromic Congenital, 2
Nail Disorder, Nonsyndromic Congenital, 3 Nail Disorder, Nonsyndromic Congenital, 1
Nail Disorder, Nonsyndromic Congenital, 5 Nail Disorder, Nonsyndromic Congenital, 4
Nail Disorder, Nonsyndromic Congenital, 7 Nail Disorder, Nonsyndromic Congenital, 8
Nail Disorder, Nonsyndromic Congenital, 9 Nonsyndromic Congenital Nail Disorder

Diseases related to Nail Disorder, Nonsyndromic Congenital, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 86)
# Related Disease Score Top Affiliating Genes
1 nail disorder, nonsyndromic congenital, 9 32.3 COL7A1 COL17A1
2 epidermolysis bullosa 30.1 KRT17 COL7A1 COL17A1
3 temple-baraitser syndrome 11.4
4 preaxial deficiency, postaxial polydactyly, and hypospadias 11.2
5 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 11.2
6 deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome 11.2
7 anonychia-ectrodactyly 11.2
8 onychodystrophy-anonychia 11.1
9 ulnar hypoplasia with mental retardation 11.1
10 anonychia-onychodystrophy with hypoplasia or absence of distal phalanges 11.1
11 deafness, congenital, with onychodystrophy, autosomal dominant 11.1
12 anonychia with flexural pigmentation 11.1
13 fontaine progeroid syndrome 11.0
14 coloboma of macula with type b brachydactyly 11.0
15 restrictive dermopathy, lethal 11.0
16 brachydactyly anonychia 11.0
17 nail disorder, nonsyndromic congenital, 6 10.9
18 santos syndrome 10.9
19 epidermolysis bullosa dystrophica, autosomal dominant 10.9
20 zimmermann-laband syndrome 1 10.9
21 fryns syndrome 10.9
22 epidermolysis bullosa, lethal acantholytic 10.9
23 autosomal dominant deafness-onychodystrophy syndrome 10.9
24 hypertrophy of the breast, juvenile 10.9
25 neurotic excoriation 10.2 COL7A1 COL17A1
26 split-hand/foot malformation 1 10.2
27 isolated split hand-split foot malformation 10.2
28 vulvar dystrophy 10.2 KRT17 COL17A1
29 blepharocheilodontic syndrome 1 10.2 COL7A1 COL17A1
30 epidermolysis bullosa, junctional, herlitz type 10.2 COL7A1 COL17A1
31 epidermolysis bullosa acquisita 10.2 COL7A1 COL17A1
32 kindler syndrome 10.1 COL7A1 COL17A1
33 epidermolysis bullosa dystrophica 10.1 COL7A1 COL17A1
34 epidermolysis bullosa simplex 10.1 KRT17 COL7A1 COL17A1
35 recessive dystrophic epidermolysis bullosa 10.0 COL7A1 COL17A1
36 acroosteolysis 10.0
37 witkop syndrome 10.0
38 craniodiaphyseal dysplasia 10.0 RSPO4 RSPO2
39 branchiootic syndrome 1 10.0
40 anonychia, total, with microcephaly 10.0
41 autosomal recessive disease 10.0
42 microcephaly 10.0
43 severe cutaneous adverse reaction 10.0
44 erythema multiforme 10.0
45 skin atrophy 10.0
46 alopecia 10.0
47 erythema multiforme major 10.0
48 x-linked intellectual disability-macrocephaly-macroorchidism syndrome 10.0
49 epidermolysis bullosa, junctional, non-herlitz type 9.9 COL7A1 COL17A1
50 uncombable hair syndrome 1 9.9

Graphical network of the top 20 diseases related to Nail Disorder, Nonsyndromic Congenital, 4:



Diseases related to Nail Disorder, Nonsyndromic Congenital, 4

Symptoms & Phenotypes for Nail Disorder, Nonsyndromic Congenital, 4

Human phenotypes related to Nail Disorder, Nonsyndromic Congenital, 4:

31
# Description HPO Frequency HPO Source Accession
1 anonychia 31 HP:0001798

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skin Nails Hair Nails:
complete absence of all fingernails (anonychia), congenital
complete absence of all toenails

Clinical features from OMIM®:

206800 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Nail Disorder, Nonsyndromic Congenital, 4 according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.4 RSPO3
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-123 9.4 PDIK1L
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 9.4 PDIK1L
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 9.4 PDIK1L
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-160 9.4 ESCO1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-169 9.4 PDIK1L
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-2 9.4 PDIK1L
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-38 9.4 ESCO1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.4 ESCO1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-76 9.4 ESCO1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-82 9.4 PDIK1L
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 9.4 PDIK1L

Drugs & Therapeutics for Nail Disorder, Nonsyndromic Congenital, 4

Search Clinical Trials , NIH Clinical Center for Nail Disorder, Nonsyndromic Congenital, 4

Cochrane evidence based reviews: anonychia congenita

Genetic Tests for Nail Disorder, Nonsyndromic Congenital, 4

Genetic tests related to Nail Disorder, Nonsyndromic Congenital, 4:

# Genetic test Affiliating Genes
1 Anonychia 29 RSPO4

Anatomical Context for Nail Disorder, Nonsyndromic Congenital, 4

MalaCards organs/tissues related to Nail Disorder, Nonsyndromic Congenital, 4:

40
Bone, Breast, Skin

Publications for Nail Disorder, Nonsyndromic Congenital, 4

Articles related to Nail Disorder, Nonsyndromic Congenital, 4:

(show all 16)
# Title Authors PMID Year
1
Anonychia congenita. 61 57 6
4702713 1973
2
RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4. 6 57
17914448 2008
3
Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. 57 6
17186469 2006
4
The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. 57 6
17041604 2006
5
Total anonychia congenita: a rare heterogeneic disorder. 57 61
15083698 2004
6
Anonychia congenita totalis: a case report and review of the literature. 57 61
12121551 2002
7
A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family. 6
18070203 2008
8
Simple anonychia. Further evidence for autosomal recessive inheritance. 57
5149532 1971
9
[Congenital complete anonychia of fingers and toes]. 57
5767934 1969
10
ANONYCHIA AS A RECESSIVE AUTOSOMAL TRAIT IN MAN. 57
14126263 1964
11
Anonychia congenita in different generations of a single Saudi family. 61
32020155 2020
12
Anonychia congenita. 61
23130298 2012
13
[An infant without nails]. 61
22217238 2011
14
A syndromic form of autosomal recessive congenital microcephaly (Jawad syndrome) maps to chromosome 18p11.22-q11.2. 61
18071751 2008
15
Total anonychia congenita in a woman with normal intelligence: report of a further case. 61
10681628 2000
16
Total anonychia congenita and microcephaly with normal intelligence: a new autosomal-recessive syndrome? 61
8985482 1996

Variations for Nail Disorder, Nonsyndromic Congenital, 4

ClinVar genetic disease variations for Nail Disorder, Nonsyndromic Congenital, 4:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RSPO4 NM_001029871.4(RSPO4):c.194A>G (p.Gln65Arg) SNV Pathogenic 1190 rs74315420 GRCh37: 20:948667-948667
GRCh38: 20:968024-968024
2 RSPO4 NM_001029871.4(RSPO4):c.319T>C (p.Cys107Arg) SNV Pathogenic 1191 rs74315421 GRCh37: 20:947907-947907
GRCh38: 20:967264-967264
3 RSPO4 NM_001029871.4(RSPO4):c.353G>A (p.Cys118Tyr) SNV Pathogenic 1192 rs74315422 GRCh37: 20:947873-947873
GRCh38: 20:967230-967230
4 RSPO4 NM_001029871.4(RSPO4):c.218G>A (p.Cys73Tyr) SNV Pathogenic 1193 rs74315423 GRCh37: 20:948643-948643
GRCh38: 20:968000-968000
5 RSPO4 NM_001029871.4(RSPO4):c.98dup (p.Asn34fs) Duplication Pathogenic 1194 rs768138495 GRCh37: 20:948762-948763
GRCh38: 20:968119-968120
6 RSPO4 NM_001029871.4(RSPO4):c.301C>T (p.Gln101Ter) SNV Pathogenic 30845 rs387907026 GRCh37: 20:947925-947925
GRCh38: 20:967282-967282
7 RSPO4 NM_001029871.4(RSPO4):c.190C>T (p.Arg64Cys) SNV Pathogenic 30846 rs387907027 GRCh37: 20:948671-948671
GRCh38: 20:968028-968028
8 RSPO4 NM_001029871.4(RSPO4):c.199G>C (p.Gly67Arg) SNV Pathogenic 30847 rs387907028 GRCh37: 20:948662-948662
GRCh38: 20:968019-968019
9 KRT17 NM_000422.3(KRT17):c.960+5G>A SNV Pathogenic 523369 rs370554150 GRCh37: 17:39777213-39777213
GRCh38: 17:41620961-41620961
10 COL17A1 NM_000494.4(COL17A1):c.4143_4144AG[1] (p.Glu1382fs) Microsatellite Pathogenic 599000 rs765243124 GRCh37: 10:105793711-105793714
GRCh38: 10:104033953-104033956
11 COL7A1 NM_000094.3(COL7A1):c.2005C>T (p.Arg669Ter) SNV Pathogenic 374052 rs780261665 GRCh37: 3:48627691-48627691
GRCh38: 3:48590258-48590258
12 COL7A1 NM_000094.3(COL7A1):c.425A>G (p.Lys142Arg) SNV Pathogenic 29636 rs121912856 GRCh37: 3:48630971-48630971
GRCh38: 3:48593538-48593538

UniProtKB/Swiss-Prot genetic disease variations for Nail Disorder, Nonsyndromic Congenital, 4:

72
# Symbol AA change Variation ID SNP ID
1 RSPO4 p.Gln65Arg VAR_030399 rs74315420
2 RSPO4 p.Cys95Phe VAR_030400 rs780506366
3 RSPO4 p.Cys107Arg VAR_030401 rs74315421
4 RSPO4 p.Cys118Tyr VAR_030402 rs74315422

Expression for Nail Disorder, Nonsyndromic Congenital, 4

Search GEO for disease gene expression data for Nail Disorder, Nonsyndromic Congenital, 4.

Pathways for Nail Disorder, Nonsyndromic Congenital, 4

Pathways related to Nail Disorder, Nonsyndromic Congenital, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.73 SEH1L RSPO4 RSPO3 RSPO2
2 11.55 RSPO4 RSPO3 RSPO2
3
Show member pathways
10.29 RSPO4 RSPO3 RSPO2

GO Terms for Nail Disorder, Nonsyndromic Congenital, 4

Biological processes related to Nail Disorder, Nonsyndromic Congenital, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Wnt signaling pathway GO:0016055 9.13 RSPO4 RSPO3 RSPO2
2 positive regulation of Wnt signaling pathway GO:0030177 8.8 RSPO4 RSPO3 RSPO2

Molecular functions related to Nail Disorder, Nonsyndromic Congenital, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent conferring tensile strength GO:0030020 8.96 COL7A1 COL17A1
2 heparin binding GO:0008201 8.8 RSPO4 RSPO3 RSPO2

Sources for Nail Disorder, Nonsyndromic Congenital, 4

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....