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Infantile-onset periodic fever-panniculitis-dermatosis syndrome(ORAS; AIPDS)

MedGen UID:
934581
Concept ID:
C4310614
Disease or Syndrome
Synonyms: Autoinflammation, panniculitis, and dermatosis syndrome; OTULIN-RELATED AUTOINFLAMMATORY SYNDROME; OTULIPENIA
SNOMED CT: Otulipenia (765435009); OTULIN (OTU deubiquitinase with linear linkage specificity) related autoinflammatory syndrome (765435009); OTU deubiquitinase with linear linkage specificity related autoinflammatory syndrome (765435009); OTULIN-related autoinflammatory syndrome (765435009); Infantile-onset periodic fever, panniculitis, dermatosis syndrome (765435009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): OTULIN (5p15.2)
 
Monarch Initiative: MONDO:0014912
OMIM®: 617099
Orphanet: ORPHA500062

Definition

Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection. Patients exhibit no overt primary immunodeficiency (Damgaard et al., 2016 and Zhou et al., 2016). [from OMIM]

Additional description

From MedlinePlus Genetics
Otulipenia is characterized by abnormal inflammation throughout the body. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, the uncontrolled inflammation that occurs in otulipenia can damage many of the body's tissues and organs, including the gastrointestinal system, joints, and skin. Disorders such as otulipenia that result from abnormally increased inflammation are known as autoinflammatory diseases.

Signs and symptoms of otulipenia usually begin within the first few weeks of life, with recurring episodes of fever; diarrhea; painful, swollen joints; and skin rashes. The skin rashes are due to inflammation of the layer of fatty tissue under the skin (panniculitis), which causes painful red bumps. Some people with otulipenia have an abnormal distribution of fatty tissue in their bodies (lipodystrophy). Affected infants have difficulty growing and gaining weight at the expected rate (failure to thrive). Damage to the body's tissues and organs caused by inflammation is life-threatening if the condition is not treated.  https://medlineplus.gov/genetics/condition/otulipenia

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Vasculitis
MedGen UID:
12054
Concept ID:
C0042384
Disease or Syndrome
Inflammation of blood vessel.
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Joint swelling
MedGen UID:
56258
Concept ID:
C0152031
Finding
The presence of swelling in a joint.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Panniculitis
MedGen UID:
45301
Concept ID:
C0030326
Disease or Syndrome
Inflammation of subcutaneous adipose tissue.
Neutrophilia
MedGen UID:
57729
Concept ID:
C0151683
Finding
Increased number of neutrophils circulating in blood.
Increased circulating IgA concentration
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Increased circulating IgM level
MedGen UID:
333454
Concept ID:
C1839972
Finding
An abnormally increased level of immunoglobulin M in blood.
Increased proportion of CD4-positive T cells
MedGen UID:
1704350
Concept ID:
C5139204
Finding
An elevation in the proportion of CD4-positive T cells relative to the total number of T cells.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInfantile-onset periodic fever-panniculitis-dermatosis syndrome

Professional guidelines

PubMed

Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, Carrizosa J, Elia M, Craiu D, Jovic NJ, Nordli D, Hirtz D, Wong V, Glauser T, Mizrahi EM, Cross JH
Epilepsia 2015 Aug;56(8):1185-97. Epub 2015 Jun 30 doi: 10.1111/epi.13057. PMID: 26122601

Recent clinical studies

Etiology

Mitta N, Menon RN, McTague A, Radhakrishnan A, Sundaram S, Cherian A, Madhavilatha GK, Mannan AU, Nampoothiri S, Thomas SV
Epilepsy Res 2020 Oct;166:106398. Epub 2020 Jun 18 doi: 10.1016/j.eplepsyres.2020.106398. PMID: 32593896
Li Y, Zhang T, Li B, Li J, Wang L, Jiang Z
Medicine (Baltimore) 2019 Dec;98(51):e18075. doi: 10.1097/MD.0000000000018075. PMID: 31860957Free PMC Article
Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, Carrizosa J, Elia M, Craiu D, Jovic NJ, Nordli D, Hirtz D, Wong V, Glauser T, Mizrahi EM, Cross JH
Epilepsia 2015 Aug;56(8):1185-97. Epub 2015 Jun 30 doi: 10.1111/epi.13057. PMID: 26122601
Ramaekers V, Sequeira JM, Quadros EV
Clin Chem Lab Med 2013 Mar 1;51(3):497-511. doi: 10.1515/cclm-2012-0543. PMID: 23314536
Ganesh R, Arvindkumar R, Vasanthi T
Clin Pediatr (Phila) 2009 Apr;48(3):271-4. Epub 2008 Oct 3 doi: 10.1177/0009922808324950. PMID: 18836058

Diagnosis

Suri D, Rawat A, Jindal AK, Vignesh P, Gupta A, Pilania RK, Joshi V, Arora K, Kumrah R, Anjani G, Aggarwal A, Phadke S, Aboobacker FN, George B, Edison ES, Desai M, Taur P, Gowri V, Pandrowala AA, Bhattad S, Kanakia S, Gottorno M, Ceccherini I, Almeida de Jesus A, Goldbach-Mansky R, Hershfield MS, Singh S
Front Immunol 2021;12:630691. Epub 2021 Mar 19 doi: 10.3389/fimmu.2021.630691. PMID: 33815380Free PMC Article
Sukumaran S, Vijayan V
JAMA Pediatr 2017 Nov 1;171(11):1122-1123. doi: 10.1001/jamapediatrics.2017.2531. PMID: 28975215
Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, Carrizosa J, Elia M, Craiu D, Jovic NJ, Nordli D, Hirtz D, Wong V, Glauser T, Mizrahi EM, Cross JH
Epilepsia 2015 Aug;56(8):1185-97. Epub 2015 Jun 30 doi: 10.1111/epi.13057. PMID: 26122601
Ramaekers V, Sequeira JM, Quadros EV
Clin Chem Lab Med 2013 Mar 1;51(3):497-511. doi: 10.1515/cclm-2012-0543. PMID: 23314536
Kossoff EH, Ferenc L, Comi AM
Epilepsia 2009 Sep;50(9):2154-7. Epub 2009 Apr 6 doi: 10.1111/j.1528-1167.2009.02072.x. PMID: 19389148

Therapy

Li Y, Zhang T, Li B, Li J, Wang L, Jiang Z
Medicine (Baltimore) 2019 Dec;98(51):e18075. doi: 10.1097/MD.0000000000018075. PMID: 31860957Free PMC Article
Cuisset JM, Sukno S, Trauffler A, Latour P, Dobbelaere D, Michaud L, Vallée L
J Med Case Rep 2016 Sep 6;10(1):241. doi: 10.1186/s13256-016-1038-9. PMID: 27599728Free PMC Article
Ramaekers V, Sequeira JM, Quadros EV
Clin Chem Lab Med 2013 Mar 1;51(3):497-511. doi: 10.1515/cclm-2012-0543. PMID: 23314536
Schara U, Christen HJ, Durmus H, Hietala M, Krabetz K, Rodolico C, Schreiber G, Topaloglu H, Talim B, Voss W, Pihko H, Abicht A, Müller JS, Lochmüller H
Eur J Paediatr Neurol 2010 Jul;14(4):326-33. Epub 2009 Nov 8 doi: 10.1016/j.ejpn.2009.09.009. PMID: 19900826
Ganesh R, Arvindkumar R, Vasanthi T
Clin Pediatr (Phila) 2009 Apr;48(3):271-4. Epub 2008 Oct 3 doi: 10.1177/0009922808324950. PMID: 18836058

Prognosis

Li Y, Zhang T, Li B, Li J, Wang L, Jiang Z
Medicine (Baltimore) 2019 Dec;98(51):e18075. doi: 10.1097/MD.0000000000018075. PMID: 31860957Free PMC Article
Chang FC, Westenberger A, Dale RC, Smith M, Pall HS, Perez-Dueñas B, Grattan-Smith P, Ouvrier RA, Mahant N, Hanna BC, Hunter M, Lawson JA, Max C, Sachdev R, Meyer E, Crimmins D, Pryor D, Morris JG, Münchau A, Grozeva D, Carss KJ, Raymond L, Kurian MA, Klein C, Fung VS
Mov Disord 2016 Jul;31(7):1033-40. Epub 2016 Apr 8 doi: 10.1002/mds.26598. PMID: 27061943Free PMC Article
Ramaekers V, Sequeira JM, Quadros EV
Clin Chem Lab Med 2013 Mar 1;51(3):497-511. doi: 10.1515/cclm-2012-0543. PMID: 23314536
Kossoff EH, Ferenc L, Comi AM
Epilepsia 2009 Sep;50(9):2154-7. Epub 2009 Apr 6 doi: 10.1111/j.1528-1167.2009.02072.x. PMID: 19389148
Ganesh R, Arvindkumar R, Vasanthi T
Clin Pediatr (Phila) 2009 Apr;48(3):271-4. Epub 2008 Oct 3 doi: 10.1177/0009922808324950. PMID: 18836058

Clinical prediction guides

Mitta N, Menon RN, McTague A, Radhakrishnan A, Sundaram S, Cherian A, Madhavilatha GK, Mannan AU, Nampoothiri S, Thomas SV
Epilepsy Res 2020 Oct;166:106398. Epub 2020 Jun 18 doi: 10.1016/j.eplepsyres.2020.106398. PMID: 32593896
Li Y, Zhang T, Li B, Li J, Wang L, Jiang Z
Medicine (Baltimore) 2019 Dec;98(51):e18075. doi: 10.1097/MD.0000000000018075. PMID: 31860957Free PMC Article
Degtyareva AV, Mikhailova SV, Zakharova EY, Tumanova EL, Puchkova AA
J Med Case Rep 2016 Jun 1;10(1):143. doi: 10.1186/s13256-016-0925-4. PMID: 27250337Free PMC Article
Bi W, Glass IA, Muzny DM, Gibbs RA, Eng CM, Yang Y, Sun A
Am J Med Genet A 2016 Aug;170(8):2181-5. Epub 2016 May 12 doi: 10.1002/ajmg.a.37727. PMID: 27170158
Brunklaus A, Ellis R, Reavey E, Forbes GH, Zuberi SM
Brain 2012 Aug;135(Pt 8):2329-36. Epub 2012 Jun 19 doi: 10.1093/brain/aws151. PMID: 22719002

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