AIADK
MCID: ATN014
MIFTS: 40

Autoinflammation with Arthritis and Dyskeratosis (AIADK)

Categories: Genetic diseases, Skin diseases

Aliases & Classifications for Autoinflammation with Arthritis and Dyskeratosis

MalaCards integrated aliases for Autoinflammation with Arthritis and Dyskeratosis:

Name: Autoinflammation with Arthritis and Dyskeratosis 56 73 29 6
Hereditary Autoinflammatory Diseases 43 71
Aiadk 56 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable features present
based on report of 2 double first cousins and 1 unrelated sporadic heterozygote (patient a)


HPO:

31
autoinflammation with arthritis and dyskeratosis:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



Summaries for Autoinflammation with Arthritis and Dyskeratosis

OMIM : 56 Autoinflammation with arthritis and dyskeratosis is characterized by recurrent fever, widespread skin dyskeratosis, arthritis, elevated biologic markers of inflammation, and mild autoimmunity with a high transitional B-cell level (summary by Grandemange et al., 2016). (617388)

MalaCards based summary : Autoinflammation with Arthritis and Dyskeratosis, also known as hereditary autoinflammatory diseases, is related to familial mediterranean fever and muckle-wells syndrome. An important gene associated with Autoinflammation with Arthritis and Dyskeratosis is NLRP1 (NLR Family Pyrin Domain Containing 1), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and Shigellosis. The drugs Colchicine and Antimitotic Agents have been mentioned in the context of this disorder. Affiliated tissues include skin, b cells and thyroid, and related phenotypes are failure to thrive and splenomegaly

UniProtKB/Swiss-Prot : 73 Autoinflammation with arthritis and dyskeratosis: A disorder characterized by recurrent fever, diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Inheritance can be autosomal dominant or autosomal recessive.

Related Diseases for Autoinflammation with Arthritis and Dyskeratosis

Diseases related to Autoinflammation with Arthritis and Dyskeratosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 familial mediterranean fever 31.3 NLRP1 IL18 CASP1
2 muckle-wells syndrome 28.7 NLRP1 IL18 CASP1
3 familial cold autoinflammatory syndrome 28.7 NLRP1 IL18 CASP1
4 cinca syndrome 28.7 NLRP1 IL18 CASP1
5 progressive familial heart block, type ia 10.2
6 vitiligo-associated multiple autoimmune disease susceptibility 6 10.2
7 vitiligo-associated multiple autoimmune disease susceptibility 1 10.2
8 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
9 left bundle branch hemiblock 10.2
10 juvenile rheumatoid arthritis 10.2
11 systemic onset juvenile idiopathic arthritis 10.2
12 periodic fever, familial, autosomal dominant 10.1
13 neurofibromatosis, type ii 9.9
14 blau syndrome 9.9
15 hyper-igd syndrome 9.9
16 mevalonic aciduria 9.9
17 synovitis 9.9
18 pyoderma 9.9
19 pyoderma gangrenosum 9.9
20 wells syndrome 9.9
21 autoinflammatory syndrome 9.9
22 schnitzler syndrome 9.7 IL18 CASP1
23 tularemia 9.7 IL18 CASP1
24 silicosis 9.7 IL18 CASP1
25 legionellosis 9.7 IL18 CASP1
26 salmonellosis 9.6 IL18 CASP1
27 shigellosis 9.6 IL18 CASP1
28 chlamydia 9.6 IL18 CASP1
29 anthrax disease 9.6 NLRP1 CASP1
30 primary bacterial infectious disease 9.6 IL18 CASP1
31 bacterial infectious disease 9.5 IL18 CASP1
32 toxoplasmosis 9.5 NLRP1 CASP1
33 bone inflammation disease 9.5 IL18 CASP1
34 renal infectious disease 9.3 NLRP1 IL18 CASP1
35 acute pancreatitis 9.2 IL18 CASP1
36 inflammatory bowel disease 8.9 NLRP1 IL18 CASP1

Graphical network of the top 20 diseases related to Autoinflammation with Arthritis and Dyskeratosis:



Diseases related to Autoinflammation with Arthritis and Dyskeratosis

Symptoms & Phenotypes for Autoinflammation with Arthritis and Dyskeratosis

Human phenotypes related to Autoinflammation with Arthritis and Dyskeratosis:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 splenomegaly 31 HP:0001744
3 hepatomegaly 31 HP:0002240
4 photophobia 31 HP:0000613
5 fever 31 HP:0001945
6 hyperkeratosis 31 HP:0000962
7 dry skin 31 HP:0000958
8 growth delay 31 HP:0001510
9 thyroiditis 31 HP:0100646
10 keratoconjunctivitis sicca 31 HP:0001097
11 corneal neovascularization 31 HP:0011496
12 uveitis 31 HP:0000554
13 autoimmune hemolytic anemia 31 HP:0001890
14 epidermal acanthosis 31 HP:0025092
15 antinuclear antibody positivity 31 HP:0003493
16 hypereosinophilia 31 HP:0032061
17 polyarticular arthritis 31 HP:0005764
18 punctate keratitis 31 HP:0011859
19 increased circulating iga level 31 HP:0003261

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive
growth retardation, moderate

Skin Nails Hair Skin Histology:
hyperkeratosis
acanthosis
prominent granular cell layer
mild papillomatosis
dyskeratotic eosinophilic cells throughout all layers
more
Laboratory Abnormalities:
hypereosinophilia
persistently elevated c-reactive protein (crp)
reduced levels of vitamin a
reduced levels of retinal-binding protein
reduced levels of vitamin c

Head And Neck Neck:
thyroiditis (patient a)

Respiratory Airways:
subglottic edema (patient a)

Abdomen Spleen:
splenomegaly (requiring splenectomy, patient a)

Skeletal Hands:
arthritis of the hands

Skin Nails Hair Hair:
hair casts

Hematology:
hemolytic anemia, autoimmune (patient a)

Head And Neck Eyes:
photophobia
corneal neovascularization
uveitis
punctate keratitis
corneal dyskeratosis
more
Immunology:
hypereosinophilia
antinuclear antibodies
elevated iga
elevated ige
chronic candidiasis (patient a)
more
Skin Nails Hair Skin:
xerosis
impaired sweating
widespread follicular hyperkeratosis
filiform hyperkeratosis
brownish-purple pigmented macules in areas of hyperkeratosis
more
Respiratory Larynx:
verrucous lesions on vocal cords

Abdomen Liver:
massive hepatomegaly (patient a)

Skeletal Limbs:
polyarticular arthritis (involving wrists, knees, and ankles)
bilateral medial metaphyseal lesions in femora
abnormal striations of distal femoral metaphyses
dense and irregular condensations in metaphyseal plates of distal femur and proximal tibia

Skin Nails Hair Nails:
dyskeratotic nails

Metabolic Features:
recurrent episodes of fever

Clinical features from OMIM:

617388

GenomeRNAi Phenotypes related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.4 CASP1 IL18 NLRP1
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.4 CASP1 IL18 NLRP1

Drugs & Therapeutics for Autoinflammation with Arthritis and Dyskeratosis

Drugs for Autoinflammation with Arthritis and Dyskeratosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Colchicine Approved Phase 4 64-86-8 6167 2833
2 Antimitotic Agents Phase 4
3 Antirheumatic Agents Phase 4
4 Antibodies, Monoclonal Phase 3
5 Immunologic Factors Phase 3
6 Antibodies Phase 3
7 Immunoglobulins Phase 3
8 Interleukin 1 Receptor Antagonist Protein Phase 3
9 Pharmaceutical Solutions Phase 3
10
Rilonacept Approved, Investigational Phase 2 501081-76-1 104924
11 Givinostat hydrochloride Phase 2
12 Histone Deacetylase Inhibitors Phase 2
13 Anti-Inflammatory Agents Phase 2

Interventional clinical trials:

(show all 23)
# Name Status NCT ID Phase Drugs
1 The Comparison of the Efficacy of Once and Twice Daily Colchicine Dosage in Pediatric Patients With Familial Mediterranean Fever: A Randomized Trial Completed NCT02602028 Phase 4 colchicine
2 A French Open-label Extension Study of Canakinumab in Patients Who Participated in International Phase III Studies CACZ885G2301E1 or CACZ885G2306 in Systemic Juvenile Idiopathic Arthritis and CACZ885N2301 in Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF) Completed NCT02334748 Phase 3 canakinumab
3 A Randomized Placebo-Controlled Study of the Efficacy and Safety of Kineret (Anakinra), in Adult Patients With Colchicine-Resistant Familial Mediterranean Fever Completed NCT01705756 Phase 3 Kineret
4 A Randomized, Double-blind, Placebo Controlled Study of Canakinumab in Patients With Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), With Subsequent Randomized Withdrawal/Dosing Frequency Reduction and Open-label Long-term Treatment Epochs Completed NCT02059291 Phase 3 Canakinumab;Placebo
5 The Effects and Side Effects of ITS2357 in Autoinflammatory Syndromes Unknown status NCT00442182 Phase 2 ITF2357
6 Controlled Ceasing of Colchicine Therapy in Familial Mediterranean Fever (FMF) Patients With Single MEFV (Mediterranean Fever) Gene Mutation Unknown status NCT02175589 Phase 2
7 An Open-label, Exploratory Study to Establish the Safety and Efficacy of 3 Months Treatment With Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever Completed NCT01088880 Phase 2 Canakinumab
8 A 6 Month Phase 2, Multi-Center, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Treatment With Canakinumab in Pediatric Patients With Colchicine Intolerant or Colchicine Resistant Familial Mediterranean Fever Completed NCT01148797 Phase 2 Canakinumab
9 An Open-label, Multicenter, Efficacy and Safety Study of 4-month Canakinumab Treatment With 6-month Follow-up in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS). Completed NCT01242813 Phase 2 ACZ885
10 Phase 2 Study of IL-1 Trap (Rilonacept) for Treatment of Familial Mediterranean Fever (FMF) Completed NCT00582907 Phase 2 Rilonacept;Placebo
11 Continuation of a Pilot Open-Label Study of IL 1 Trap in Adult Subjects With Autoinflammatory Diseases: A Therapeutic Approach to Study Pathogenesis Completed NCT00094900 Phase 2 IL-1 Trap
12 Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study Recruiting NCT03446209 Phase 2 Tocilizumab Infusion RoAcemtra (EU);0.9% physiological saline
13 An Open-label, Parallel-group, Multiple-Dose, Pharmacokinetic and Safety Study of Colchicine Pediatric Formulation in Pediatric and Adult Patients With FMF Completed NCT01075906 Phase 1 colchicine sprinkle capsules;colchicine sprinkle capsules
14 Exertional Muscle Fatigue In FMF Patients Evaluated By MRI And MR Spectroscopy Of The Thigh Unknown status NCT00658060
15 Gluten-related Disorders in Patients Affected With Familial Mediterranean Fever Completed NCT03563300
16 Genetics and Pathophysiology of Autoinflammatory Disorders. Recruiting NCT00001373
17 Creation of a Tool to Assess Quality of Life in Patient With Auto-inflammatory Diseases Active, not recruiting NCT03569644
18 Heat Intolerance in the Group of FMF Patients Enrolling by invitation NCT01059279
19 Assessment of a Functional Test to Detect Familial Mediterranean Fever Not yet recruiting NCT03747315
20 Immunome Project Consortium for Autoinflammatory Disorders Not yet recruiting NCT03919110
21 Musculoskeletal Ultrasound of the Ankles in Erysipelas-like Erythema of Familial Mediterranean Fever Not yet recruiting NCT03917277
22 The Effect of Probiotics on Response to Therapy and on Adverse Effect in Patients Treated With Colchicine for Familial Mediterranean Fever. Withdrawn NCT02021084
23 Inflammatory Proteins in Familial Mediterranean Fever During Attack and Remission Withdrawn NCT00323440

Search NIH Clinical Center for Autoinflammation with Arthritis and Dyskeratosis

Cochrane evidence based reviews: hereditary autoinflammatory diseases

Genetic Tests for Autoinflammation with Arthritis and Dyskeratosis

Genetic tests related to Autoinflammation with Arthritis and Dyskeratosis:

# Genetic test Affiliating Genes
1 Autoinflammation with Arthritis and Dyskeratosis 29 NLRP1

Anatomical Context for Autoinflammation with Arthritis and Dyskeratosis

MalaCards organs/tissues related to Autoinflammation with Arthritis and Dyskeratosis:

40
Skin, B Cells, Thyroid, Testes, T Cells, Bone, Heart

Publications for Autoinflammation with Arthritis and Dyskeratosis

Articles related to Autoinflammation with Arthritis and Dyskeratosis:

# Title Authors PMID Year
1
A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis). 61 56 6
27965258 2017
2
Vitamin a deficiency phrynoderma associated with chronic giardiasis. 56 6
16918630 2006
3
Transient left bundle branch block and left ventricular dysfunction in a patient with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome. 61
30681047 2019
4
Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. 61
30291141 2018
5
A clinical update on inflammasomopathies. 61
28387826 2017

Variations for Autoinflammation with Arthritis and Dyskeratosis

ClinVar genetic disease variations for Autoinflammation with Arthritis and Dyskeratosis:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NLRP1 NM_033004.4(NLRP1):c.3641C>G (p.Pro1214Arg)SNV Pathogenic 393320 rs1057524876 17:5424986-5424986 17:5521666-5521666
2 NLRP1 NM_033004.4(NLRP1):c.2176C>T (p.Arg726Trp)SNV Uncertain significance 393319 rs776245016 17:5461840-5461840 17:5558520-5558520

Expression for Autoinflammation with Arthritis and Dyskeratosis

Search GEO for disease gene expression data for Autoinflammation with Arthritis and Dyskeratosis.

Pathways for Autoinflammation with Arthritis and Dyskeratosis

GO Terms for Autoinflammation with Arthritis and Dyskeratosis

Cellular components related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NLRP1 inflammasome complex GO:0072558 8.62 NLRP1 CASP1

Biological processes related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine-mediated signaling pathway GO:0019221 9.37 IL18 CASP1
2 regulation of apoptotic process GO:0042981 9.32 NLRP1 CASP1
3 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.26 NLRP1 CASP1
4 regulation of inflammatory response GO:0050727 9.16 NLRP1 CASP1
5 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043280 8.96 NLRP1 CASP1
6 positive regulation of interleukin-1 beta secretion GO:0050718 8.62 NLRP1 CASP1

Molecular functions related to Autoinflammation with Arthritis and Dyskeratosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0008656 8.62 NLRP1 CASP1

Sources for Autoinflammation with Arthritis and Dyskeratosis

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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