NDNC4
MCID: NLD014
MIFTS: 42

Nail Disorder, Nonsyndromic Congenital, 4 (NDNC4)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases
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Aliases & Classifications for Nail Disorder, Nonsyndromic Congenital, 4

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

Name: Nail Disorder, Nonsyndromic Congenital, 4 57 71
Anonychia Congenita 57 11 19 42 12 43
Anonychia 42 75 28 5 31
Hyponychia Congenita 11 42 73
Nonsyndromic Congenital Nail Disorder 4 11 14
Anonychia/hyponychia Congenita 57 73
Isolated Congenital Anonychia 19 58
Anonychia Congenita Totalis 58 73
Ndnc4 57 73
Autosomal Recessive Nonsyndromic Congenital Nail Disorder-4 19
Nail Disorder, Nonsyndromic, Congenital, Type 4 38
Nail Disorder, Non-Syndromic Congenital, 4 73
Nonsyndromic Congenital Nail Disorder, 4 19
Congenital Absence of Nails 42
Congenital Anonychia 19
Isolated Anonychia 58
Anonychia Totalis 57
Aplastic Nails 42
Absent Nails 42

Characteristics:


Inheritance:

Nail Disorder, Nonsyndromic Congenital, 4: Autosomal recessive 57
Isolated Congenital Anonychia: Autosomal dominant,Autosomal recessive 58
Anonychia Congenita Totalis: Autosomal recessive 58

Prevelance:

Isolated Congenital Anonychia: <1/1000000 (Worldwide) 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
patients have no abnormalities of hair, teeth, or bone


Classifications:

Orphanet: 58  
Rare skin diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 11 DOID:0080082
OMIM® 57 206800
OMIM Phenotypic Series 57 PS161050
ICD10 31 Q84.3
ICD10 via Orphanet 32 Q84.3
UMLS via Orphanet 72 C0265998
SNOMED-CT via HPO 69 23610003
UMLS 71 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 08-Dec-2022)

MalaCards based summary: Nail Disorder, Nonsyndromic Congenital, 4, also known as anonychia congenita, is related to epidermolysis bullosa and coloboma of macula with type b brachydactyly. An important gene associated with Nail Disorder, Nonsyndromic Congenital, 4 is RSPO4 (R-Spondin 4), and among its related pathways/superpathways is Keratinization. Affiliated tissues include bone, skin and bone marrow, and related phenotype is anonychia.

MedlinePlus Genetics: 42 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.

Orphanet: 58 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.

Disease Ontology: 11 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.

UniProtKB/Swiss-Prot: 73 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.

Wikipedia: 75 Anonychia is the absence of fingernails or toenails, an anomaly which may be the result of a congenital... more...

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 107)
# Related Disease Score Top Affiliating Genes
1 epidermolysis bullosa 30.3 KRT17 COL7A1 COL17A1
2 coloboma of macula with type b brachydactyly 11.3
3 temple-baraitser syndrome 11.2
4 deafness, congenital, with onychodystrophy, autosomal dominant 11.2
5 preaxial deficiency, postaxial polydactyly, and hypospadias 11.2
6 anonychia-ectrodactyly 11.2
7 anonychia, total, with microcephaly 11.2
8 ulnar hypoplasia with mental retardation 11.2
9 onychodystrophy-anonychia 11.2
10 ulna hypoplasia-intellectual disability syndrome 11.2
11 anonychia with flexural pigmentation 11.1
12 hypertrophy of the breast, juvenile 11.0
13 jawad syndrome 11.0
14 brachydactyly anonychia 11.0
15 nail disorder, nonsyndromic congenital, 6 11.0
16 santos syndrome 11.0
17 epidermolysis bullosa dystrophica, autosomal dominant 10.9
18 zimmermann-laband syndrome 1 10.9
19 epidermolysis bullosa, junctional 1a, intermediate 10.9
20 fryns syndrome 10.9
21 triphalangeal thumbs with brachyectrodactyly 10.9
22 mammary-digital-nail syndrome 10.9
23 psoriasis 14, pustular 10.9
24 nail dysplasia, isolated congenital 10.9
25 neurotic excoriation 10.3 COL7A1 COL17A1
26 split-hand/foot malformation 1 10.3
27 split hand-foot malformation 10.3
28 isolated split hand-split foot malformation 10.3
29 mucinoses 10.2 KRT74 KRT71
30 junctional epidermolysis bullosa non-herlitz type 10.2 COL7A1 COL17A1
31 woolly hair, autosomal dominant 10.2 KRT74 KRT71
32 hypotrichosis 3 10.2 KRT74 KRT71
33 epidermolysis bullosa, junctional 1b, severe 10.2 COL7A1 COL17A1
34 hypotrichosis 4 10.2 KRT74 KRT71
35 hypotrichosis 13 10.2 KRT74 KRT71
36 hypotrichosis 8 10.2 KRT74 KRT71
37 epidermolysis bullosa, junctional 5b, with pyloric atresia 10.2 COL7A1 COL17A1
38 epidermolysis bullosa simplex 1a, generalized severe 10.2 KRT74 COL7A1
39 pompholyx 10.2 EDARADD COL17A1
40 epidermolysis bullosa simplex 10.2 KRT17 COL7A1 COL17A1
41 pachyonychia congenita 1 10.2 KRT74 KRT17 COL7A1
42 recessive dystrophic epidermolysis bullosa 10.1 COL7A1 COL17A1
43 palmoplantar keratoderma, epidermolytic 10.1 KRT17 COL7A1
44 hypotrichosis 6 10.1 KRT81 KRT74 KRT71
45 epidermolytic hyperkeratosis 10.1 KRT81 KRT17 COL7A1
46 familial woolly hair syndrome 10.1 KRT81 KRT74 KRT71
47 acroosteolysis 10.1
48 witkop syndrome 10.1
49 epidermolysis bullosa acquisita 10.1 COL7A1 COL17A1
50 hypotrichosis 10.0 KRT74 KRT71 EDARADD

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:

30
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 anonychia 30 HP:0001798

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Skin Nails Hair Nails:
complete absence of all fingernails (anonychia), congenital
complete absence of all toenails

Clinical features from OMIM®:

206800 (Updated 08-Dec-2022)

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 28 RSPO4

Anatomical Context for Nail Disorder, Nonsyndromic Congenital, 4

Organs/tissues related to Nail Disorder, Nonsyndromic Congenital, 4:

MalaCards : Bone, Skin, Bone Marrow, Tongue, Heart, Breast, Liver

Publications for Nail Disorder, Nonsyndromic Congenital, 4

Articles related to Nail Disorder, Nonsyndromic Congenital, 4:

(show top 50) (show all 173)
# Title Authors PMID Year
1
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. 62 57 5
17914448 2008
2
A novel missense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a consanguineous Pakistani family. 62 57 5
18070203 2008
3
Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. 62 57 5
17186469 2006
4
The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. 62 57 5
17041604 2006
5
Anonychia congenita. 62 57 5
4702713 1973
6
Total anonychia congenita: a rare heterogeneic disorder. 62 57
15083698 2004
7
Anonychia congenita totalis: a case report and review of the literature. 62 57
12121551 2002
8
Simple anonychia. Further evidence for autosomal recessive inheritance. 62 57
5149532 1971
9
[Congenital complete anonychia of fingers and toes]. 62 57
5767934 1969
10
ANONYCHIA AS A RECESSIVE AUTOSOMAL TRAIT IN MAN. 62 57
14126263 1964
11
Anonychia Congenita - Rare Inheritance of a Rare Disorder. 62
35057601 2022
12
Acquired anonychia secondary to onychotemnomania. 62
35962490 2022
13
Congenital Nail Disorders among Children with Suspected Ectodermal Dysplasias. 62
36421794 2022
14
Congenital anonychia: A distinctive nail finding in a newborn. 62
36129199 2022
15
Description of the most severe signs in nail lichen planus: a strategy to contribute to the diagnosis of the severe stage. 62
35325468 2022
16
Doors Syndrome: Case Report. 62
36092206 2022
17
A rare case of Acrodermatitis continua of Hallopeau successfully treated with topical calcipotriol/betamethasone dipropionate ointment associated with Jaccaud's arthropathy: A case report. 62
36406304 2022
18
Porokeratosis of the Nail Unit: Case Series and Review. 62
34901183 2021
19
Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium. 62
34099859 2021
20
Pterygium Complicating Nail Psoriasis and Trachyonychia: Is It Rare? 62
34307478 2021
21
Nail Changes in Lichen Planus: A Single-Center Study. 62
33336579 2021
22
Review of Nail Lichen Planus: Epidemiology, Pathogenesis, Diagnosis, and Treatment. 62
33745635 2021
23
Squamous Cell Carcinoma Arising in Ungual Lichen Planus: Report and Review. 62
33614721 2021
24
Mammalian-specific ectodermal enhancers control the expression of Hoxc genes in developing nails and hair follicles. 62
33199643 2020
25
Brachydactyly-anonychia with congenital absent phalanges of the hand. 62
32068944 2020
26
A novel mutation in LMX1B gene in a newborn with nail-patella syndrome: Clinical and dermoscopic findings. 62
32892417 2020
27
A 17q24.3 duplication identified in a large Chinese family with brachydactyly-anonychia. 62
32583964 2020
28
[Lichenoid drug eruption with antituberculosis drugs associated with an anonychia]. 62
32229034 2020
29
Nail Changes in Leprosy: An Observational Study of 125 Patients. 62
32477978 2020
30
Anonychia congenita in different generations of a single Saudi family. 62
32020155 2020
31
Congenital Absence of Nails and Digital-Type Thumb due to Prenatal Phenytoin Exposure. 62
31122647 2019
32
Total Anonychia, Spastic Diplegia, and Mental Retardation in an Indian Boy: A Novel Syndrome? 62
31896855 2019
33
Nail Changes in S├ęzary Syndrome: A Single-Center Study and Review of the Literature. 62
30917680 2019
34
Severe digital malformations in a rare variant of fibrodysplasia ossificans progressiva. 62
31012264 2019
35
Acrodermatitis continua of Hallopeau: clinical perspectives. 62
31497529 2019
36
Iso-Kikuchi Syndrome: Report of 3 Pediatric Cases. 62
29102318 2018
37
Acral porokeratosis associated with anonychia. 62
29271370 2018
38
Progressive reticulate skin pigmentation and anonychia in a patient with bone marrow failure. 62
29033247 2017
39
Santos syndrome is caused by mutation in the WNT7A gene. 62
28855715 2017
40
Congenital non-syndromic anonychia totalis with acroosteolysis. 62
29122908 2017
41
Congenital Anonychia and Uncombable Hair Syndrome: Coinheritance of Homozygous Mutations in RSPO4 and PADI3. 62
28087452 2017
42
Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails. 62
28003643 2017
43
A novel mutation in the RSPO4 gene in a patient with autosomal recessive anonychia. 62
28247548 2017
44
Distal limb anomalies in patients with congenital dyserythropoietic anemia. 62
27759939 2017
45
Anonychia with absent phalanges and brachydactyly: A report of two unrelated cases. 62
27320764 2016
46
Dual genetic diagnoses: Atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1. 62
26590955 2016
47
Hoyeraal-Hreidarsson Syndrome due to PARN Mutations: Fourteen Years of Follow-Up. 62
26810774 2016
48
Congenital anonychia. 62
25881976 2016
49
RBBP8 syndrome with microcephaly, intellectual disability, short stature and brachydactyly. 62
26333564 2015
50
Scaly plaque with pustules and anonychia on the middle finger. 62
26761938 2015

Variations for Nail Disorder, Nonsyndromic Congenital, 4

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

5 (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) DUP 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 COL7A1 NM_000094.4(COL7A1):c.2005C>T (p.Arg669Ter) SNV Pathogenic
374052 rs780261665 GRCh37: 3:48627691-48627691
GRCh38: 3:48590258-48590258
11 COL7A1 NM_000094.4(COL7A1):c.425A>G (p.Lys142Arg) SNV Pathogenic
29636 rs121912856 GRCh37: 3:48630971-48630971
GRCh38: 3:48593538-48593538
12 COL17A1 NM_000494.4(COL17A1):c.4145_4148del (p.Glu1382fs) MICROSAT Pathogenic
599000 rs765243124 GRCh37: 10:105793711-105793714
GRCh38: 10:104033953-104033956

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

73
# 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
11.56 KRT81 KRT74 KRT71 KRT38 KRT17

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 keratin filament GO:0045095 9.56 KRT81 KRT74 KRT71 KRT17
2 intermediate filament GO:0005882 9.32 KRT81 KRT74 KRT71 KRT38 KRT222 KRT17

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

# Name GO ID Score Top Affiliating Genes
1 keratinization GO:0031424 9.56 KRT81 KRT74 KRT71 KRT17
2 intermediate filament organization GO:0045109 9.32 KRT81 KRT74 KRT71 KRT38 KRT17

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

# Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 9.56 SEH1L KRT38 KRT222 KRT17
2 structural constituent of skin epidermis GO:0030280 9.1 KRT81 KRT74 KRT71

Sources for Nail Disorder, Nonsyndromic Congenital, 4

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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