NDNC4
MCID: NLD014
MIFTS: 38

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 72
Anonychia Congenita 57 12 53 25 37 13 44
Anonychia 25 29 6 33
Hyponychia Congenita 12 25 74
Anonychia/hyponychia Congenita 57 74
Isolated Congenital Anonychia 53 59
Anonychia Congenita Totalis 59 74
Ndnc4 57 74
Autosomal Recessive Nonsyndromic Congenital Nail Disorder-4 53
Nail Disorder, Nonsyndromic, Congenital, Type 4 40
Nail Disorder, Non-Syndromic Congenital, 4 74
Nonsyndromic Congenital Nail Disorder, 4 53
Nonsyndromic Congenital Nail Disorder 4 12
Congenital Absence of Nails 25
Congenital Anonychia 53
Isolated Anonychia 59
Anonychia Totalis 57
Aplastic Nails 25
Absent Nails 25

Characteristics:

Orphanet epidemiological data:

59
isolated congenital anonychia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide);
anonychia congenita totalis
Inheritance: Autosomal recessive;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
nail disorder, nonsyndromic congenital, 4:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080082
KEGG 37 H00683
ICD10 33 Q84.3
ICD10 via Orphanet 34 Q84.3
UMLS via Orphanet 73 C0265998
UMLS 72 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)

MalaCards based summary : Nail Disorder, Nonsyndromic Congenital, 4, also known as anonychia congenita, is related to epidermolysis bullosa and anonychia-ectrodactyly. An important gene associated with Nail Disorder, Nonsyndromic Congenital, 4 is RSPO4 (R-Spondin 4). Affiliated tissues include bone and skin, and related phenotype is anonychia.

Disease Ontology : 12 A nail disease that is characterized by absence of fingernails and toenails, has material basis in homozygous or compound heterozygous mutation in the R-spondin-4 gene on chromosome 20p13.

Genetics Home Reference : 25 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.

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79143DefinitionIsolated 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.Visit the Orphanet disease page for more resources.

KEGG : 37
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 : 74 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 Nail Disorder, Nonsyndromic Congenital, 10

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

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 epidermolysis bullosa 29.1 COL7A1 COL17A1
2 anonychia-ectrodactyly 12.4
3 anonychia-onychodystrophy with brachydactyly type b and ectrodactyly 12.4
4 anonychia with flexural pigmentation 12.3
5 brachydactyly anonychia 12.3
6 nail disorder, nonsyndromic congenital, 9 12.0
7 temple-baraitser syndrome 11.9
8 deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures syndrome 11.6
9 santos syndrome 11.5
10 anonychia-onychodystrophy with hypoplasia or absence of distal phalanges 11.4
11 ulnar hypoplasia with mental retardation 11.4
12 preaxial deficiency, postaxial polydactyly, and hypospadias 11.4
13 onychodystrophy-anonychia 11.3
14 ulna hypoplasia-intellectual disability syndrome 11.3
15 coloboma of macula with type b brachydactyly 11.3
16 restrictive dermopathy, lethal 11.3
17 nail disorder, nonsyndromic congenital, 6 11.3
18 fontaine progeroid syndrome 11.2
19 hypertrophy of the breast, juvenile 11.2
20 deafness, congenital, with onychodystrophy, autosomal dominant 11.2
21 zimmermann-laband syndrome 1 11.2
22 fryns syndrome 11.1
23 psoriatic arthritis 11.1
24 epidermolysis bullosa, lethal acantholytic 11.1
25 zimmermann-laband syndrome 2 11.1
26 autosomal dominant deafness-onychodystrophy syndrome 11.1
27 dominant dystrophic epidermolysis bullosa 11.1
28 split-hand/foot malformation 1 10.4
29 isolated split hand-split foot malformation 10.4
30 acroosteolysis 10.2
31 witkop syndrome 10.2
32 severe cutaneous adverse reaction 10.2
33 erythema multiforme 10.2
34 skin atrophy 10.2
35 alopecia 10.2
36 erythema multiforme major 10.2
37 x-linked intellectual disability-macrocephaly-macroorchidism syndrome 10.2
38 anonychia, total, with microcephaly 10.2
39 autosomal recessive disease 10.2
40 microcephaly 10.2
41 uncombable hair syndrome 1 10.0
42 brachydactyly 10.0
43 pemphigus 10.0
44 lichen planus 10.0
45 depression 10.0
46 acromial dimples 10.0
47 brachydactyly, type b1 10.0
48 brachydactyly-ectrodactyly with fibular aplasia or hypoplasia 10.0
49 chromosome 2q35 duplication syndrome 10.0
50 fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly 10.0

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:

32
# Description HPO Frequency HPO Source Accession
1 anonychia 32 HP:0001798

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Nails:
complete absence of all fingernails (anonychia), congenital
complete absence of all toenails

Clinical features from OMIM:

206800

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:

41
Bone, Skin

Publications for Nail Disorder, Nonsyndromic Congenital, 4

Articles related to Nail Disorder, Nonsyndromic Congenital, 4:

(show all 15)
# Title Authors PMID Year
1
Anonychia congenita. 38 8 71
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. 8 71
17914448 2008
3
Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. 8 71
17186469 2006
4
The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. 8 71
17041604 2006
5
Total anonychia congenita: a rare heterogeneic disorder. 38 8
15083698 2004
6
Anonychia congenita totalis: a case report and review of the literature. 38 8
12121551 2002
7
A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family. 71
18070203 2008
8
Simple anonychia. Further evidence for autosomal recessive inheritance. 8
5149532 1971
9
[Congenital complete anonychia of fingers and toes]. 8
5767934 1969
10
ANONYCHIA AS A RECESSIVE AUTOSOMAL TRAIT IN MAN. 8
14126263 1964
11
Anonychia congenita. 38
23130298 2012
12
[An infant without nails]. 38
22217238 2011
13
A syndromic form of autosomal recessive congenital microcephaly (Jawad syndrome) maps to chromosome 18p11.22-q11.2. 38
18071751 2008
14
Total anonychia congenita in a woman with normal intelligence: report of a further case. 38
10681628 2000
15
Total anonychia congenita and microcephaly with normal intelligence: a new autosomal-recessive syndrome? 38
8985482 1996

Variations for Nail Disorder, Nonsyndromic Congenital, 4

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

6 (show all 12)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 COL7A1 NM_000094.3(COL7A1): c.2005C> T (p.Arg669Ter) single nucleotide variant Pathogenic rs780261665 3:48627691-48627691 3:48590258-48590258
2 KRT17 NM_000422.3(KRT17): c.960+5G> A single nucleotide variant Pathogenic rs370554150 17:39777213-39777213 17:41620961-41620961
3 RSPO4 NM_001029871.4(RSPO4): c.194A> G (p.Gln65Arg) single nucleotide variant Pathogenic rs74315420 20:948667-948667 20:968024-968024
4 RSPO4 NM_001029871.4(RSPO4): c.319T> C (p.Cys107Arg) single nucleotide variant Pathogenic rs74315421 20:947907-947907 20:967264-967264
5 RSPO4 NM_001029871.4(RSPO4): c.353G> A (p.Cys118Tyr) single nucleotide variant Pathogenic rs74315422 20:947873-947873 20:967230-967230
6 RSPO4 NM_001029871.4(RSPO4): c.218G> A (p.Cys73Tyr) single nucleotide variant Pathogenic rs74315423 20:948643-948643 20:968000-968000
7 RSPO4 NM_001029871.4(RSPO4): c.98dup (p.Asn34fs) duplication Pathogenic rs768138495 20:948763-948763 20:968120-968120
8 COL7A1 NM_000094.3(COL7A1): c.425A> G (p.Lys142Arg) single nucleotide variant Pathogenic rs121912856 3:48630971-48630971 3:48593538-48593538
9 RSPO4 NM_001029871.4(RSPO4): c.301C> T (p.Gln101Ter) single nucleotide variant Pathogenic rs387907026 20:947925-947925 20:967282-967282
10 RSPO4 NM_001029871.4(RSPO4): c.190C> T (p.Arg64Cys) single nucleotide variant Pathogenic rs387907027 20:948671-948671 20:968028-968028
11 RSPO4 NM_001029871.4(RSPO4): c.199G> C (p.Gly67Arg) single nucleotide variant Pathogenic rs387907028 20:948662-948662 20:968019-968019
12 COL17A1 NM_000494.4(COL17A1): c.4143_4144AG[1] (p.Glu1382fs) short repeat Pathogenic 10:105793710-105793714 10:104033953-104033956

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

74
# 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

GO Terms for Nail Disorder, Nonsyndromic Congenital, 4

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

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.54 RSPO4 COL7A1 COL17A1
2 extracellular matrix GO:0031012 9.32 COL7A1 COL17A1
3 endoplasmic reticulum lumen GO:0005788 9.26 COL7A1 COL17A1
4 collagen-containing extracellular matrix GO:0062023 9.16 COL7A1 COL17A1
5 basement membrane GO:0005604 8.96 COL7A1 COL17A1
6 collagen trimer GO:0005581 8.62 COL7A1 COL17A1

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 8.96 COL7A1 COL17A1
2 epidermis development GO:0008544 8.8 KRT17 COL7A1 COL17A1

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 8.62 COL7A1 COL17A1

Sources for Nail Disorder, Nonsyndromic Congenital, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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