Diagnostic Tools/Genetic Testing

 Diagnostic Tools for Autoinflammatory Diseases

Genetic testing and other helpful resources for periodic fever syndromes.

autoinflamamtory databaseSystemic Autoinflammatory Diseases Database

Edited and Co-authored by Autoinflammatory Alliance President Karen Durrant, RN BSN and leading experts on autoinflammatory diseases, this free online database describes the notable symptoms of currently known autoinflammatory syndromes. This database has become a highly respected and important diagnostic tool for doctors around the world. Since these diseases can be very similar and have overlapping symptoms, the chart can help narrow down which SAIDs to consider for a patient and can help guide further testing.

Eurofever Classification Criteria

This diagnostic questionnaire by the EUROFEVER project is really helpful for doctors considering symptoms when trying to diagnose some of the hereditary periodic fever (autoinflammatory) syndromes, like CAPS, TRAPS, HIDS and FMF.

Genetic Testing

For many of the periodic fever syndromes/autoflammatory diseases, there is genetic testing available to help with diagnosis. Genetic testing for mutations on genes known to cause autoinflammatory diseases can also be used to help rule out possible syndromes when making a clinical diagnosis. Often insurance will cover the full cost of these tests, but check with your provider to determine if these tests are covered.

Since many of the autoinflammatory diseases share similar symptoms that may include recurrent high fevers, mouth ulcers, swollen lymph nodes, rashes, joint pain and/or swelling and other symptoms, running a fever panel that tests for multiple syndromes at once is both efficient and cost effective. It also reduces the chances of missing the cause of the symptoms or missing comorbid conditions when an individual patient has genetics for multiple autoinflammatory diseases.

The most common fever syndrome PFAPA does not have a genetic test, but ruling out fever syndromes that can have similar symptoms, such as HIDS, CAPS, FMF, Behcet-like familial autoinflammatory syndrome (HA20) and TRAPS is important when diagnosing PFAPA. Doctors Lawson and Hersh state, “The various periodic fever syndromes have overlapping symptoms; therefore, a definitive diagnosis of PFAPA cannot be made until other periodic fever syndromes have been excluded via genetic testing…

fever syndrome genetic testing

DNA photo by Mike_Kiev/Bigstockphoto.com

There are several labs in the U.S. that have panels available for periodic fever syndromes. Below are the commonly used panels. All use next generation DNA sequencing and are very accurate tests.

The larger panels by Invitae, MNG Laboratories, Blueprint Genetics, Prevention Genetics, and Fulgent test for several fever syndromes and other conditions that may have similar symptoms, recurring fevers, recurring symptoms, and/or involve cytokine dysregulation. Some genes included in these panels are related to autoimmune diseases, immune deficiencies, and inflammatory bowel diseases.

Invitae has a 207 gene panel here that includes several autoinflammatory, autoimmune, and immunodeficiency genes in one panel. Invitae’s patient pay price is $250.

GeneDx’s XomeDxSlice Tool is available for doctors to create a customized panel of up to 150 genes. Panels of more than 150 genes are an option with GeneDx clinical staff review. This is a more comprehensive and economical option then the 7-gene autoinflammatory panel.

Autoinflammatory Genetic Panel Comparisons; Genes Tested by Lab

Use the search box to search for a specific gene or disease and to see what labs include that condition in their panel. Below the chart, use the scroll bar or the "Next" button to see more labs and genes. On a phone you can swipe to move the chart and see all the labs.
 GeneDx XomeDxSlice ToolMNG LaboratoriesFulgentInvitaeBlueprint GeneticsPrevention GeneticsARUP Laboratories and GeneDx
Number of GenesUp to 150. 150+ genes review. 362820725137
CostPrice unlisted. Compassionate care pricing/payment plans available. Will bill insurance.$1995 Bills contracted institutions. Self-pay available.Price unlisted. Will bill insurance. Patient assistance/ payment plans available.Patient-pay price $250 Will bill insurance.$1400 Will bill insurance. Financial assistance available.$1440 Will bill insurance.Price unlisted. Will bill insurance.
Test NameXomeDxSlice ToolFever SyndromesPeriodic Fever/Autoinflammatory Disorders NGS PanelPrimary Immunodeficiency Panel (Includes Autoinflammatory)Autoinflammatory Syndrome PanelPeriodic Fever Syndromes Sequencing PanelPeriodic Fever Syndromes Panel
Gene/Syndrome      
MEFV – Familial Mediterranean Fever (FMF)X-per doctor requestXXXXXX
LPIN2 – Majeed SyndromeX-per doctor requestXXXXXX
MVK – Mevalonate Kinase Deficiencies (MKD): HIDS and MAX-per doctor requestXXXXXX
NLRP3 – Cryopyrin Associated Periodic Syndromes (CAPS): MWS, FCAS, and NOMIDX-per doctor requestXXXXXX
PSTPIP1 – Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA)X-per doctor requestXXXXXX
TNFRSF1A – Tumor Necrosis Factor (TNF) – Associated Periodic Syndrome (TRAPS)X-per doctor requestXXXXXX
ELANE - Cyclic neutropeniaX-per doctor requestXXXXXX
ABCB1 – Inflammatory bowel disease 13 X-per doctor request      
ACP5 - Spondyloenchondrodysplasia with immune dysregulationX-per doctor request  XX  
ADAM17 - Inflammatory skin and bowel disease, neonatal 1X-per doctor request  X   
Aicardi-Goutieres syndromes (AGS) - TREX1 (AGS1), RNASEH2B (AGS2), RNASEH2C (AGS3), RNASEH2A (AGS4), SAMHD1 (AGS5), ADAR (AGS6), and IFIH1 (AGS7)X-per doctor request  XX  
AP1S3 - Pustular psoriasis (PSORS15)X-per doctor request X    
ATG16L1 – Increased risk for Crohn’s diseaseX-per doctor request      
CARD14 – Familial psoriasis (PSORS2)X-per doctor requestXXXXX 
CECR1/ADA2 – Deficiency of adenosine deaminase 2 (DADA2), aka Fever with early onset stroke (FEOS)X-per doctor requestXXX   
COPA - COPA syndrome, aka Autoimmune interstitial lung, joint, and kidney diseaseX-per doctor request  X   
DDX58 - Singleton-Merten syndrome
X-per doctor request   X  
FOXP3 - IPEX syndromeX-per doctor requestX  X   
GCH1 - Dopa-responsive dystonia, Tetrahydrobiopterin deficiencyX-per doctor requestX     
HAX1 - Severe congenital neutropeniaX-per doctor request X    
HLA-C - Psoriasis susceptibility 1, Human immunodeficiency virus type 1, susceptibility toX-per doctor request      
HTR1A - Periodic fever, menstrual cycle-dependent (PFMC)X-per doctor requestX     
IL10, IL10RA, IL10RB – Early-onset inflammatory bowel disease (EO-IBD25, EO-IBD28, and EO-IBD with Il-10 deficiency)X-per doctor requestXXX   
IL1RN – Deficiency of interleukin-1ß (IL-1ß) receptor antagonist (DIRA)X-per doctor requestXXXX  
IL23A – Risk for inflammatory demyelinating diseasesX-per doctor request      
IL23R – Risk for: ankylosing spondylitis, Crohn’s, psoriatic arthritis, ulcerative colitis, psoriasisX-per doctor request      
IL36RN – Deficiency of interleukin-36-receptor antagonist (DITRA)X-per doctor requestXXXXX 
IL6 – Risk for juvenile rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease 1X-per doctor request      
IRF5 – Risk for autoimmune disorders: lupus, rheumatoid arthritis, systemic scleroderma, ulcerative colitisX-per doctor request      
IRGM – Risk for Crohn’s diseaseX-per doctor request      
ISG15 - Immunodeficiency 38 with basal ganglia calcification (IMD38)X-per doctor request   XX  
NCSTN – Hidradenitis suppurativaX-per doctor request      
NEFL - Charcot-Marie-tooth diseaseX-per doctor requestX     
NFAT5 - NFAT5 haploinsufficiencyX-per doctor request  X   
NLRC4 – NLRC4 Macrophage activation-like syndrome (NLRC4-MAS)X-per doctor request XX   
NLRP1 - NLRP1-associated autoinflammation with arthritis and dyskeratosis (NAIAD), Risk for: Autoimmune Addison disease, vitiligo, autoimmune disordersX-per doctor requestX
NLRP7 - Recurrent hydatidiform moleX-per doctor requestXX    
NLRP12 – Familial cold autoinflammatory syndrome 2 (FCAS2)X-per doctor requestXXXXX 
NOD2 – Blau syndromeX-per doctor requestXXXXX 
ORAI1 - Myopathy, tubular aggregate, 2 (TAM2), Immunodeficiency 9 (IMD9)X-per doctor requestX  X   
PLCG2 – PLCG2-associated antibody deficiency & immune dysregulation (PLAID) or Familial atypical cold urticaria (FACU) or FCAS3 and APLAIDX-per doctor requestXXXX  
PSENEN - Hidradenitis suppurativaX-per doctor request      
PSMB8 - Chronic atypical neurtophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE)X-per doctor requestXXXXX 
PTPN2 – Risk for ulcerative colitisX-per doctor request      
RBCK1 - Polyglucosan body myopathy 1 with or without immunodeficiency (PGBM1), HOIL-1 deficiency
X-per doctor requestXXX   
SCO2 - Myopia 6 (MYP6), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (CEMCOX1)X-per doctor requestX     
SH3BP2 – CherubismX-per doctor requestXXX   
SLC19A3 - Biotin-thiamine-responsive basal ganglia diseaseX-per doctor requestX     
SLC25A19 - Amish lethal microcephaly. Leigh syndromeX-per doctor requestX     
SLC29A3 – SLC29A3 Spectrum disorder, aka H. syndrome; Pigmented hypertrichosis with insulin-dependent diabetes mellitus (IDDM)X-per doctor requestXXX   
TLR3 - Human immunodeficiency virus type 1, susceptibility toX-per doctor requestX  X   
TMEM173 – STING-associated vasculopathy with onset in infancy (SAVI)X-per doctor requestXX XX  
TNFAIP3 - Haploinsufficiency of A20 (HA20), aka Behcet-like familial autoinflammatory syndromeX-per doctor request    X 
TNFRSF11A – TNFRSF11A-associated hereditary fever disease (TRAPS11)X-per doctor requestXX    
TPK1 - Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5)X-per doctor requestX     
TRAF3 - Herpes simplex encephalitis, susceptibility toX-per doctor requestX  X   
TRAF3IP2 - Psoriasis susceptibility 13, Candidiasis, familial, 8X-per doctor request   X   
TRNT1 - Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)X-per doctor requestXX   
ACD-Dyskeratosis congenitaX-per doctor requestX
ACTB-Baraitser-Winter syndromeX-per doctor requestX
ADA-severe combined immunodeficiency (SCID)X-per doctor requestX
AICDA-Immunodeficiency with hyper-IgM 2 (HIGM2)X-per doctor requestX
AIRE-autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)X-per doctor requestX
AK2-Reticular dysgenesis (RDYS)X-per doctor requestX
AP3B1-Hermansky Pudlak syndromeX-per doctor requestX
ATM- ataxia-telangiectasiaX-per doctor requestX
B2M-Amyloidosis 8 (AMYL8), Immunodeficiency 43 (IMD43)X-per doctor requestX
BCL10-Immunodeficiency 37 (IMD37)X-per doctor requestX
BLNK-Agammaglobulinemia 4X-per doctor requestX
BLOC1S6-Hermansky-Pudlak syndromeX-per doctor requestX
BTK-isolated growth hormone deficiency type III,X-linked agammaglobulinemia (XLA)X-per doctor requestX
CARD11-atopic dermatitis, immune system disordersX-per doctor requestX
CARD9-chronic mucocutaneous candidiasisX-per doctor requestX
CASP10&CASP8-Autoimmune lymphoproliferative syndromeX-per doctor requestX
CD247-Immunodeficiency 25 (IMD25)X-per doctor requestX
CD27-Lymphoproliferative syndrome 2 (LPFS2)X-per doctor requestX
CD3D-Immunodeficiency 19X-per doctor requestX
CD3E-Immunodeficiency 18X-per doctor requestX
CD3G-Immunodeficiency 17X-per doctor requestX
CD40LG-X-linked hyper IgM syndromeX-per doctor requestX
CD79A-Agammaglobulinemia 3X-per doctor requestX
CD79B-Agammaglobulinemia 6X-per doctor requestX
CD8A-Cd8 deficiency, familialX-per doctor requestX
CEBPE-Specific granule deficiencyX-per doctor requestX
CHD7-CHARGE syndromeX-per doctor requestX
CIITA-autoimmune Addison disease, bare lymphocyte syndrome type II (BLS II)X-per doctor requestX
CLPB-CLPB deficiencyX-per doctor requestX
CORO1A-Immunodeficiency 8X-per doctor requestX
CR2-Systemic lupus erythematosus, Common variable immune deficiencyX-per doctor requestX
CSF2RA-Surfactant dysfunctionX-per doctor requestX
CSF3R-Severe congenital neutropeniaX-per doctor requestX
CTC1-Coats plus syndromeX-per doctor requestX
CYBA-chronic granulomatous diseaseX-per doctor requestX
Chronic granulomatous disease- CYBA, CYBB, NCF2, NCF4X-per doctor requestX
DOCK8-utosomal recessive hyper-IgE syndromeX-per doctor requestX
Familial Hemophagocytic Lymphohistiocytosis- PRF1, STX11, STXBP2, RAB27A, UNC13D, SH2DIAX-per doctor requestX
SPINK5-Netherton syndromeX-per doctor requestX

XIAP-X-linked familial hemophagocytic lymphohistiocytosis

X-per doctor requestX

About Benign Variant Reports

Many labs no longer report all variant or novel mutations on the initial report provided to doctors. To get the full variant report, doctors must make a request for the benign variant/novel report from the lab. Click here for more information.

Genetic Testing Registry

You can search this registry to find genetic testing available around the world here.

Finding Doctors

To find a doctor experienced with fever syndromes, contact the Autoinflammatory Alliance here.

Becoming an Empowered Patient: A Toolkit for the Undiagnosed

This kit put out by the Global Genes Project has everything you need to navigate the medical system when trying to find a diagnosis for any rare condition. It includes information on staying organized, how to talk to doctors, how to get your medical records, and much more.

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