AIADK
MCID: ATN014
MIFTS: 39

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 57 73 29 6
Hereditary Autoinflammatory Diseases 44 71
Aiadk 57 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
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
Onset and clinical course infantile onset


Classifications:



Summaries for Autoinflammation with Arthritis and Dyskeratosis

OMIM® : 57 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) (Updated 05-Mar-2021)

MalaCards based summary : Autoinflammation with Arthritis and Dyskeratosis, also known as hereditary autoinflammatory diseases, is related to familial mediterranean fever and periodic fever, familial, autosomal dominant. 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 Pathways and Cytosolic sensors of pathogen-associated DNA. The drugs Colchicine and Tubulin Modulators have been mentioned in the context of this disorder. 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 45)
# Related Disease Score Top Affiliating Genes
1 familial mediterranean fever 31.1 NLRP1 IL18 CASP1
2 periodic fever, familial, autosomal dominant 29.8 IL18 CASP1
3 mevalonic aciduria 29.6 IL18 CASP1
4 meningitis 29.4 IL18 CASP1
5 cinca syndrome 29.4 NLRP1 IL18 CASP1
6 familial cold autoinflammatory syndrome 29.2 NLRP1 IL18 CASP1
7 muckle-wells syndrome 29.2 NLRP1 IL18 CASP1
8 respiratory papillomatosis, juvenile recurrent, congenital 11.0
9 arthritis 10.3
10 brucellosis 10.2
11 progressive familial heart block, type ia 10.2
12 vitiligo-associated multiple autoimmune disease susceptibility 6 10.2
13 vitiligo-associated multiple autoimmune disease susceptibility 1 10.2
14 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
15 left bundle branch hemiblock 10.2
16 juvenile rheumatoid arthritis 10.2
17 blau syndrome 10.0
18 hyper-igd syndrome 10.0
19 aseptic meningitis 10.0
20 plica syndrome 10.0
21 synovitis 10.0
22 pyoderma 10.0
23 acne 10.0
24 pyoderma gangrenosum 10.0
25 bacterial meningitis 10.0
26 wells syndrome 10.0
27 autoinflammatory syndrome 10.0
28 congenital toxoplasmosis 9.9 NLRP1 IL18
29 schnitzler syndrome 9.8 IL18 CASP1
30 streptococcus pneumonia 9.8 IL18 CASP1
31 silicosis 9.8 IL18 CASP1
32 salmonellosis 9.8 IL18 CASP1
33 legionellosis 9.8 IL18 CASP1
34 shigellosis 9.8 IL18 CASP1
35 toxoplasmosis 9.8 NLRP1 CASP1
36 chlamydia 9.8 IL18 CASP1
37 anthrax disease 9.8 NLRP1 CASP1
38 primary bacterial infectious disease 9.7 IL18 CASP1
39 bacterial infectious disease 9.7 IL18 CASP1
40 bone inflammation disease 9.7 IL18 CASP1
41 acute pancreatitis 9.7 IL18 CASP1
42 chronic granulomatous disease 9.6 IL18 CASP1
43 behcet syndrome 9.6 IL18 CASP1
44 renal infectious disease 9.5 NLRP1 IL18 CASP1
45 crohn's disease 9.5 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 23)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 very rare (1%) HP:0001508
2 splenomegaly 31 very rare (1%) HP:0001744
3 hepatomegaly 31 very rare (1%) HP:0002240
4 photophobia 31 very rare (1%) HP:0000613
5 dry skin 31 very rare (1%) HP:0000958
6 growth delay 31 very rare (1%) HP:0001510
7 thyroiditis 31 very rare (1%) HP:0100646
8 uveitis 31 very rare (1%) HP:0000554
9 corneal neovascularization 31 very rare (1%) HP:0011496
10 keratoconjunctivitis sicca 31 very rare (1%) HP:0001097
11 follicular hyperkeratosis 31 very rare (1%) HP:0007502
12 elevated c-reactive protein level 31 very rare (1%) HP:0011227
13 recurrent fever 31 very rare (1%) HP:0001954
14 palmoplantar hyperkeratosis 31 very rare (1%) HP:0000972
15 autoimmune hemolytic anemia 31 very rare (1%) HP:0001890
16 increased circulating iga level 31 very rare (1%) HP:0003261
17 antinuclear antibody positivity 31 very rare (1%) HP:0003493
18 polyarticular arthritis 31 very rare (1%) HP:0005764
19 hypereosinophilia 31 very rare (1%) HP:0032061
20 increased circulating igg level 31 very rare (1%) HP:0003237
21 punctate keratitis 31 very rare (1%) HP:0011859
22 laryngeal papilloma 31 very rare (1%) HP:0033001
23 epidermal acanthosis 31 HP:0025092

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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
uveitis
corneal neovascularization
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 (Updated 05-Mar-2021)

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 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-1 9.26 CASP1
2 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-2 9.26 CASP1 IL18 NLRP1
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.02 IL18 NLRP1
4 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.02 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 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Colchicine Approved Phase 4 64-86-8 6167 2833
2 Tubulin Modulators Phase 4
3 Antirheumatic Agents Phase 4
4 Antimitotic Agents Phase 4
5 Pharmaceutical Solutions Phase 3
6 Interleukin 1 Receptor Antagonist Protein Phase 3
7
Rilonacept Approved, Investigational Phase 2 501081-76-1 104924
8 Anti-Inflammatory Agents Phase 2
9 Kallikreins Phase 2

Interventional clinical trials:

(show all 28)
# 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 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
3 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
4 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
5 Controlled Ceasing of Colchicine Therapy in Familial Mediterranean Fever (FMF) Patients With Single MEFV (Mediterranean Fever) Gene Mutation Unknown status NCT02175589 Phase 2
6 Phase 2 Study of IL-1 Trap (Rilonacept) for Treatment of Familial Mediterranean Fever (FMF) Completed NCT00582907 Phase 2 Rilonacept;Placebo
7 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
8 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
9 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
10 Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study Completed NCT03446209 Phase 2 Tocilizumab Infusion RoAcemtra (EU);0.9% physiological saline
11 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
12 Factor XII-associated Cold Autoinflammatory Syndrome (FACAS) Linked to Kallikrein-kinin Pathology: Proof of Concept Treatment With Lanadelumab (DX-2930) Recruiting NCT04278885 Phase 2 Lanadelumab
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 Assessment of a Functional Test to Detect Familial Mediterranean Fever Unknown status NCT03747315
16 Gluten-related Disorders in Patients Affected With Familial Mediterranean Fever Completed NCT03563300
17 An Exploratory Study of the Genetics, Pathophysiology, and Natural History of Autoinflammatory Diseases Recruiting NCT00001373
18 The Movement Imagery Ability in Patients With Familial Mediterranean Fever Recruiting NCT04729218
19 Creation of a Tool to Assess Quality of Life in Patient With Auto-inflammatory Diseases Active, not recruiting NCT03569644
20 Heat Intolerance in the Group of FMF Patients Enrolling by invitation NCT01059279
21 Comparison the Effectiveness of Online Aerobic Dance Exercises Versus Physical Activity Counseling in Patients With Juvenile Familial Mediterranean Fever Enrolling by invitation NCT04724993
22 The Effect of Pilates Based Exercise Practice on Physical and Psychological Parameters in Patients With Behçet and Familial Mediterranean Fever. Enrolling by invitation NCT04402255
23 Pain, Sleep, Fatigue, Physical Activity Level, Quality of Life and Exercise Habits in Patients With Familial Mediterranean Fever and Behçet: Analysis Before and After Covid19 Pandemic Enrolling by invitation NCT04403438
24 Immunome Project Consortium for Autoinflammatory Disorders Not yet recruiting NCT03919110
25 Musculoskeletal Ultrasound of the Ankles in Erysipelas-like Erythema of Familial Mediterranean Fever Not yet recruiting NCT03917277
26 Characterization of a Functional Test for Mediterranean Family Fever Screening - 2 Not yet recruiting NCT04478409
27 The Effect of Probiotics on Response to Therapy and on Adverse Effect in Patients Treated With Colchicine for Familial Mediterranean Fever. Withdrawn NCT02021084
28 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

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). 6 57 61
27965258 2017
2
Vitamin a deficiency phrynoderma associated with chronic giardiasis. 57 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.2170G>A (p.Glu724Lys) SNV Uncertain significance 931045 17:5461846-5461846 17:5558526-5558526
3 NLRP1 NM_033004.4(NLRP1):c.790del (p.Cys264fs) Deletion Uncertain significance 808210 rs1597460588 17:5463226-5463226 17:5559906-5559906
4 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

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

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.13 NLRP1 IL18 CASP1
2
Show member pathways
12 IL18 CASP1
3 11.87 IL18 CASP1
4 11.72 NLRP1 CASP1
5 11.69 NLRP1 IL18 CASP1
6 11.57 IL18 CASP1
7
Show member pathways
11.46 NLRP1 CASP1
8 11.12 IL18 CASP1
9 10.74 NLRP1 IL18 CASP1
10 10.14 NLRP1 IL18 CASP1
11 10 IL18 CASP1

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 interleukin-1 beta production GO:0032731 8.96 NLRP1 CASP1
6 pyroptosis GO:0070269 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
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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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