Getting a Diagnosis/Genetic Testing

Genetic testing and other helpful diagnostic resources for autoinflammatory diseases.

Click here for a printable PDF of these resources.

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 SAID a patient may have 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.

fever syndrome genetic testing

DNA photo by Mike_Kiev/Bigstockphoto.com

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, and TRAPS is important when diagnosing PFAPA. Genetic testing is one important tool to use to help rule out other fever syndromes along with other labs and an evaluation of clinical symptoms. 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…

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 MNG Laboratoris, Blueprint Genetics, and Fulgent test for several fever syndromes and some 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 immune deficiencies.

Gene/SyndromeMNG LaboratoriesFulgentBlueprint GeneticsARUP Laboratories and GeneDx
Gene/SyndromeMNG LaboratoriesFulgentBlueprint GeneticsARUP Laboratories and GeneDx
Number of Genes3721257
Cost (Pricing is as of December 2016. Contact the lab for updated pricing.)$1995. Only bills institutions contracted with. Self pay available. Click here for price sheet. Pricing not listed on website. Will bill insurance. Patient assistance and payment plans offered.$1400. Will bill insurance. Offers, "financial assistance and/or a flexible payment plan to eligible patients."Pricing not listed on website. Will bill insurance.
Test Name Fever Syndromes NextGen DNA Sequencing Panel (37 Genes). Test Code: NGS319Periodic Fever/Autoinflammatory Disorders NGS Panel. Autoinflammatory Syndrome Panel. Test Code: IM0201Periodic Fever Syndromes Panel Click here for ARUP panel. Click here for GeneDx panel.
MEFV – Familial Mediterranean Fever (FMF)XXXX
LPIN2 – Majeed SyndromeXXXX
MVK – Mevalonate Kinase Deficiencies (MKD): HIDS and MAXXXX
NLRP3 – Cryopyrin Associated Periodic Syndromes (CAPS): MWS, FCAS, and NOMIDXXXX
PSTPIP1 – Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA)XXXX
TNFRSF1A – Tumor Necrosis Factor (TNF) – Associated Periodic Syndrome (TRAPS)XXXX
ELANE - Cyclic neutropeniaXXXX
CARD14 – Familial Psoriasis (PSORS2)XXX
IL1RN – Deficiency of Interleukin-1ß (IL-1ß) Receptor Antagonist (DIRA)XXX
IL36RN – Deficiency of Interleukin-36-Receptor Antagonist (DITRA)XXX
NLRP12 – Familial Cold Autoinflammatory Syndrome 2 (FCAS2)XXX
PLCG2 – PLCG2-associated Antibody Deficiency & Immune Dysregulation (PLAID) or Familial Atypical Cold Urticaria (FACU) or FCAS3 and APLAIDXXX
NOD2 – Blau SyndromeXXX
PSMB8 – Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome (CANDLE)XXX
IL10, IL10RA, IL10RB – Early-Onset Inflammatory Bowel Disease (Eo-IBD25, EO-IBD28, and EO-IBD with Il-10 deficiency)XX
SH3BP2 – CherubismXX
SLC29A3 – SLC29A3 Spectrum Disorder, aka H. syndrome; Pigmented Hypertrichosis with Insulin-dependent Diabetes Mellitus (IDDM)XX
TNFRSF11A – TNFRSF11A-associated hereditary fever disease (TRAPS11)XX
TMEM173 – STING-associated vasculopathy with onset in infancy (SAVI)XX
AP1S3 – Pustular Psoriasis (PSORS15)X
CECR1 – Deficiency of Adenosine Deaminase 2 (DADA2) – aka Fever with Early Onset Stroke (FEOS)X
NLRC4 – NLRC4 Macrophage Activation-like Syndrome (NLRC4-MAS)X
TRNT1 - Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)X
Aicardi-Goutieres syndromes (AGS): TREX1 (AGS1), RNASEH2B (AGS2), RNASEH2C (AGS3), RNASEH2A (AGS4), SAMHD1 (AGS5), ADAR (AGS6), and IFIH1 (AGS7) X
NLRP7 - Recurrent hydatidiform moleXX
GCH1 - Dopa-responsive dystonia, Tetrahydrobiopterin deficiencyX
HTR1A - Periodic fever, menstrual cycle-dependent (PFMC)X
NEFL - Charcot-Marie-Tooth diseaseX
ORAI1 - Myopathy, tubular aggregate, 2 (TAM2), Immunodeficiency 9 (IMD9)X
RANBP2 - Encephalopathy, acute, infection-induced, 3 (IIAE3)X
RBCK1 - Polyglucosan body myopathy 1 with or without immunodeficiency (PGBM1)X
SCO2 - Myopia 6 (MYP6), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (CEMCOX1)X
SLC19A3 - biotin-thiamine-responsive basal ganglia diseaseX
SLC25A19 - Amish lethal microcephalyX
TLR3 - Human immunodeficiency virus type 1, susceptibility toX
TPK1 - Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5)X
TRAF3 - Herpes simplex encephalitis, susceptibility toX
ACP5 - Spondyloenchondrodysplasia with immune dysregulationX
DDX58 - Singleton-Merten syndromeX
ISG15 - Immunodeficiency 38 with basal ganglia calcification (IMD38)X

Some labs, such as GeneDx, 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 this 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.