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Sterile multifocal osteomyelitis with periostitis and pustulosis(DIRA; OMPP; CRMO2)

MedGen UID:
411230
Concept ID:
C2748507
Disease or Syndrome
Synonyms: CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS 2, WITH PERIOSTITIS AND PUSTULOSIS; Interleukin 1 Receptor Antagonist Deficiency
SNOMED CT: Autoinflammatory disease due to interleukin-1 receptor antagonist deficiency (773702002); Interleukin-1 receptor antagonist deficiency (773702002); OMPP - sterile osteomyelitis, multifocal with periostitis and pustulosis (773702002); Sterile multifocal osteomyelitis with periostitis and pustulosis (773702002)
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): IL1RN (2q14.1)
 
Monarch Initiative: MONDO:0013021
OMIM®: 612852
Orphanet: ORPHA210115

Definition

Chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2) is an autosomal recessive multisystemic autoinflammatory disorder characterized by onset of symptoms in early infancy. Affected individuals present with joint swelling and pain, pustular rash, oral mucosal lesions, and fetal distress. The disorder progresses in severity to generalized severe pustulosis or ichthyosiform lesions and diffuse bone lesions. Radiographic studies show widening of the anterior rib ends, periosteal elevation along multiple long bones, multifocal osteolytic lesions, heterotopic ossification, and metaphyseal erosions of the long bones. Laboratory studies show elevation of inflammatory markers. The disorder results from unopposed activation of the IL1 inflammatory signaling pathway. Treatment with the interleukin-1 receptor antagonist anakinra may result in clinical improvement (Aksentijevich et al., 2009). For a discussion of genetic heterogeneity of CRMO, see 609628. [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Failure to thrive in infancy
MedGen UID:
358083
Concept ID:
C1867873
Finding
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Periostitis
MedGen UID:
45816
Concept ID:
C0031111
Disease or Syndrome
Inflammation of the periosteum
Joint swelling
MedGen UID:
56258
Concept ID:
C0152031
Finding
The presence of swelling in a joint.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
Flaring of rib cage
MedGen UID:
381496
Concept ID:
C1854780
Finding
The presence of wide, concave anterior rib ends.
Fused cervical vertebrae
MedGen UID:
854386
Concept ID:
C3887527
Congenital Abnormality
A congenital anomaly characterized by a joining (fusion) of two or more cervical vertebral bodies with one another.
Osteolysis
MedGen UID:
1648424
Concept ID:
C4721411
Pathologic Function
Osteolysis refers to the destruction of bone through bone resorption with removal or loss of calcium.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Abscess
MedGen UID:
1684
Concept ID:
C0000833
Disease or Syndrome
An abscess is a localized collection of purulent material surrounded by inflammation and granulation.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Stomatitis
MedGen UID:
52511
Concept ID:
C0038362
Disease or Syndrome
Stomatitis is an inflammation of the mucous membranes of any of the structures in the mouth.
Neutrophilia
MedGen UID:
57729
Concept ID:
C0151683
Finding
Increased number of neutrophils circulating in blood.
Pustule
MedGen UID:
488804
Concept ID:
C0241157
Finding
A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
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.
Epidermal acanthosis
MedGen UID:
65136
Concept ID:
C0221270
Finding
Diffuse hypertrophy or thickening of the stratum spinosum of the epidermis (prickle cell layer of the skin).
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Fetal distress
MedGen UID:
5164
Concept ID:
C0015930
Pathologic Function
An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Sterile multifocal osteomyelitis with periostitis and pustulosis in Orphanet.

Recent clinical studies

Therapy

Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgård U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R
N Engl J Med 2009 Jun 4;360(23):2426-37. doi: 10.1056/NEJMoa0807865. PMID: 19494218Free PMC Article

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