MCID: CFF003
MIFTS: 51

Caffey Disease

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Caffey Disease

MalaCards integrated aliases for Caffey Disease:

Name: Caffey Disease 53 12 72 23 49 24 55 71 13 51 14
Infantile Cortical Hyperostosis 53 12 23 49 24 55 71 36 28
Cortical Congenital Hyperostosis 12 69
Hyperostosis Cortical Infantile 72 49
Hyperostosis, Cortical, Congenital 41
Caffey-Silverman Syndrome 24
De Toni-Caffey Disease 24
Caffd 71

Characteristics:

Orphanet epidemiological data:

55
caffey disease
Inheritance: Autosomal dominant; Age of onset: Antenatal,Childhood,Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant


HPO:

31
caffey disease:
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Incomplete penetrance based on family history or molecular genetic testing has been noted [newberg & tampas 1981, cho et al 2008]. in a family studied by gensure et al [2005], 19 of 24 (79%) individuals with the defining col1a1 pathogenic variant had a clinical history of an episode consistent with caffey disease...

Classifications:



External Ids:

OMIM 53 114000
Disease Ontology 12 DOID:4257
ICD10 32 M89.8
MeSH 41 D006958
SNOMED-CT 64 123258003 24752008
Orphanet 55 ORPHA1310
UMLS via Orphanet 70 C0020497
ICD10 via Orphanet 33 M89.8
KEGG 36 H00613
UMLS 69 C0020497

Summaries for Caffey Disease

Genetics Home Reference : 24 Caffey disease, also called infantile cortical hyperostosis, is a bone disorder that most often occurs in babies. Excessive new bone formation (hyperostosis) is characteristic of Caffey disease. The bone abnormalities mainly affect the jawbone, shoulder blades (scapulae), collarbones (clavicles), and the shafts (diaphyses) of long bones in the arms and legs. Affected bones may double or triple in width, which can be seen by x-ray imaging. In some cases two bones that are next to each other, such as two ribs or the pairs of long bones in the forearms (radius and ulna) or lower legs (tibia and fibula) become fused together. Babies with Caffey disease also have swelling of joints and of soft tissues such as muscles, with pain and redness in the affected areas. Affected infants can also be feverish and irritable.

MalaCards based summary : Caffey Disease, also known as infantile cortical hyperostosis, is related to hyperostosis and ehlers-danlos/osteogenesis imperfecta syndrome, and has symptoms including soft-tissue swelling, bone lesions and irritability. An important gene associated with Caffey Disease is COL1A1 (Collagen Type I Alpha 1 Chain), and among its related pathways/superpathways are ECM-receptor interaction and Binding and Uptake of Ligands by Scavenger Receptors. Affiliated tissues include bone, testes and cortex, and related phenotypes are cellular and behavior/neurological

UniProtKB/Swiss-Prot : 71 Caffey disease: Characterized by an infantile episode of massive subperiosteal new bone formation that typically involves the diaphyses of the long bones, mandible, and clavicles. The involved bones may also appear inflamed, with painful swelling and systemic fever often accompanying the illness. The bone changes usually begin before 5 months of age and resolve before 2 years of age.

NIH Rare Diseases : 49 Caffey disease is a bone disorder that most often occurs in babies. It is characterized by the excessive formation of new bone (hyperostosis) in the jaw, shoulder blades, collarbones, and shafts of long bones in the arms and legs. Affected bones may double or triple in width. In some cases, two bones that are next to each other may become fused. Caffey disease is caused by a mutation in the COL1A1 gene. It is inherited in an autosomal dominant pattern, but not all people who inherit the mutation develop signs and symptoms. This is due to incomplete penetrance.  Last updated: 4/15/2014

Disease Ontology : 12 A bone inflammation disease that causes bone changes, soft tissue swelling and irritability in infants. The disease has been associated with COL1A1 gene. It has symptom soft-tissue swelling, has symptom bone lesions, and has symptom irritability.

Wikipedia : 72 Infantile cortical hyperostosis is a self-limited inflammatory disorder of infants that causes bone... more...

Description from OMIM: 114000
GeneReviews: NBK99168

Related Diseases for Caffey Disease

Diseases related to Caffey Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 hyperostosis 10.4
2 ehlers-danlos/osteogenesis imperfecta syndrome 10.4 COL1A1 COL1A2
3 ehlers-danlos syndrome, arthrochalasia type, 1 10.4 COL1A1 COL1A2
4 high bone mass osteogenesis imperfecta 10.4 COL1A1 COL1A2
5 larsen-like syndrome 10.3 COL1A1 COL1A2
6 osteogenesis imperfecta, type viii 10.3 COL1A1 COL1A2
7 osteogenesis imperfecta, type vi 10.3 COL1A1 COL1A2
8 dentinogenesis imperfecta 10.2 COL1A1 COL1A2
9 cellulitis 10.2
10 osteogenesis imperfecta, type vii 10.2 CD36 COL1A1 COL1A2
11 scleroderma, familial progressive 10.2 CD36 COL1A1 COL1A2
12 ehlers-danlos syndrome, classic type, 1 10.2 CD36 COL1A1 COL1A2
13 osteogenesis imperfecta, type v 10.2 CD36 COL1A1 COL1A2
14 osteogenesis imperfecta, type iv 10.2 CD36 COL1A1 COL1A2
15 bruck syndrome 10.1 CD36 COL1A1 COL1A2
16 osteogenesis imperfecta, type ii 10.1 CD36 COL1A1 COL1A2
17 osteogenesis imperfecta, type i 10.1 CD36 COL1A1 COL1A2
18 osteogenesis imperfecta, type iii 10.1 CD36 COL1A1 COL1A2
19 brittle bone disorder 10.1 CD36 COL1A1 COL1A2
20 phosphorus metabolism disease 10.1 FAM20C GALNT3
21 otosclerosis 10.1 CD36 COL1A1 COL1A2
22 spondyloepiphyseal dysplasia congenita 10.1 COL1A1 COL1A2
23 secondary hypertrophic osteoarthropathy 10.1 GALNT3 SLCO2A1
24 qualitative platelet defect 10.0 CD36 F3
25 gray platelet syndrome 10.0 CD36 CD40LG
26 bone development disease 10.0 COL1A1 COL1A2
27 thrombocytosis 9.9
28 thrombasthenia 9.9 CD36 F3
29 connective tissue disease 9.9 CD40LG COL1A1 COL1A2
30 collagen disease 9.8 COL1A1 COL1A2
31 down syndrome 9.8
32 calcinosis 9.8
33 cervicitis 9.8
34 fournier gangrene 9.8 CD40LG F3
35 heparin-induced thrombocytopenia 9.8 CD40LG F3
36 hantavirus pulmonary syndrome 9.7 CD40LG F3
37 catastrophic antiphospholipid syndrome 9.7 CD40LG F3
38 splenic disease 9.7 CD40LG F3
39 korean hemorrhagic fever 9.7 CD40LG F3
40 hemorrhagic fever 9.7 CD40LG F3
41 branch retinal artery occlusion 9.7 CD40LG F3
42 endocardium disease 9.7 CD40LG F3
43 scrub typhus 9.7 CD40LG F3
44 blood coagulation disease 9.6 CD40LG F3
45 dengue hemorrhagic fever 9.5 CD40LG F3

Graphical network of the top 20 diseases related to Caffey Disease:



Diseases related to Caffey Disease

Symptoms & Phenotypes for Caffey Disease

Symptoms via clinical synopsis from OMIM:

53
Misc:
fever
usually appears by 5 months of age
specific bones involved different in familial and sporadic cases

Limbs:
mild congenital leg curvature

Lab:
thickened periosteum and infiltration of the deeper layers of the periosteum with round cells

Skel:
hot, tender swelling of involved bones (e.g., mandible, ribs)

Radiology:
identified by x-ray in the fetus in utero
cortical hyperostosis
curved tibia
irregularity of bone cortex


Clinical features from OMIM:

114000

Symptoms:

12
  • soft-tissue swelling
  • bone lesions
  • irritability

Human phenotypes related to Caffey Disease:

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 fever 55 31 frequent (33%) Frequent (79-30%) HP:0001945
2 hyperesthesia 55 31 frequent (33%) Frequent (79-30%) HP:0100963
3 respiratory insufficiency 55 31 occasional (7.5%) Occasional (29-5%) HP:0002093
4 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
5 behavioral abnormality 55 31 frequent (33%) Frequent (79-30%) HP:0000708
6 feeding difficulties in infancy 55 31 occasional (7.5%) Occasional (29-5%) HP:0008872
7 cellulitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0100658
8 proptosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000520
9 facial asymmetry 55 31 occasional (7.5%) Occasional (29-5%) HP:0000324
10 calvarial hyperostosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0004490
11 cortical irregularity 55 31 hallmark (90%) Very frequent (99-80%) HP:0005731
12 cortical thickening of long bone diaphyses 55 31 occasional (7.5%) Occasional (29-5%) HP:0005791
13 periosteal thickening of long tubular bones 55 31 frequent (33%) Frequent (79-30%) HP:0006465
14 increased antibody level in blood 55 31 occasional (7.5%) Occasional (29-5%) HP:0010702
15 tibial bowing 31 HP:0002982

MGI Mouse Phenotypes related to Caffey Disease:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.01 CD36 CD40LG COL1A1 COL1A2 F3 FAM20C
2 behavior/neurological MP:0005386 10 A4GALT CD36 COL1A1 COL1A2 F3 FAM20C
3 cardiovascular system MP:0005385 9.98 CD36 CD40LG COL1A1 COL1A2 F3 GALNT3
4 homeostasis/metabolism MP:0005376 9.97 A4GALT CD36 CD40LG COL1A1 COL1A2 F3
5 hematopoietic system MP:0005397 9.91 SCARF2 F3 FAM20C GALNT3 CD36 CD40LG
6 immune system MP:0005387 9.86 COL1A1 F3 FAM20C GALNT3 SCARF2 A4GALT
7 limbs/digits/tail MP:0005371 9.55 COL1A1 COL1A2 FAM20C GALNT3 SCARF2
8 renal/urinary system MP:0005367 9.43 CD36 CD40LG COL1A1 FAM20C GALNT3 SLCO2A1
9 skeleton MP:0005390 9.17 CD36 CD40LG COL1A1 COL1A2 FAM20C GALNT3

Drugs & Therapeutics for Caffey Disease

Search Clinical Trials , NIH Clinical Center for Caffey Disease

Cochrane evidence based reviews: hyperostosis, cortical, congenital

Genetic Tests for Caffey Disease

Genetic tests related to Caffey Disease:

# Genetic test Affiliating Genes
1 Infantile Cortical Hyperostosis 28 COL1A1

Anatomical Context for Caffey Disease

MalaCards organs/tissues related to Caffey Disease:

38
Bone, Testes, Cortex

Publications for Caffey Disease

Articles related to Caffey Disease:

(show all 39)
# Title Authors Year
1
Prenatal Presentation of Lethal Variant Infantile Cortical Hyperostosis (Caffey Disease). ( 27110654 )
2016
2
Familial mutation in Caffey disease with reduced penetrance: A case report. ( 29090879 )
2016
3
Prenatal Caffey disease (prenatal cortical hyperostosis): severe forms with favorable outcome. ( 25630842 )
2015
4
Two Japanese familial cases of Caffey disease with and without the common COL1A1 mutation and normal bone density, and review of the literature. ( 24390061 )
2014
5
Caffey disease: New perspectives on old questions. ( 24389367 )
2013
6
Infantile cortical hyperostosis (Caffey disease): a case report and review of the literature--where are we after 70 years? ( 23522764 )
2013
7
Tumoral calcinosis of the cervical spine and its association with Caffey disease in a 4-month-old boy: case report and review of the literature. ( 22080299 )
2012
8
Caffey disease in neonatal period: the importance of the family! ( 23047998 )
2012
9
Severe thrombocytosis as initial manifestation of Caffey disease in a 4 month old infant. ( 22213629 )
2012
10
Prenatal Caffey disease. ( 21443040 )
2011
11
COL1A1 mutation in an Indian child with Caffey disease. ( 21249479 )
2011
12
Infantile cortical hyperostosis (Caffey disease): a possible misdiagnosis as physical abuse. ( 20890006 )
2010
13
Caffey disease. ( 20967539 )
2010
14
Caffey disease or infantile cortical hyperostosis: a case report. ( 22125716 )
2010
15
Contribution of three-dimensional computed tomography in prenatal diagnosis of lethal infantile cortical hyperostosis (Caffey disease). ( 19455587 )
2009
16
Prenatal cortical hyperostosis (Caffey disease) with Down syndrome. ( 19280500 )
2009
17
Infantile cortical hyperostosis (Caffey disease): a review. ( 18848116 )
2008
18
The c.3040C > T mutation in COL1A1 is recurrent in Korean patients with infantile cortical hyperostosis (Caffey disease). ( 18704262 )
2008
19
Caffey disease with raised immunoglobulin levels and thrombocytosis. ( 18334802 )
2008
20
Expanding the phenotypic spectrum of Caffey disease. ( 17309652 )
2007
21
A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. ( 15864348 )
2005
22
Caffey disease: an unlikely collagenopathy. ( 15864344 )
2005
23
Caffey disease in a 6-month-old girl. ( 14735359 )
2004
24
Antenatal onset of cortical hyperostosis (Caffey disease): case report and review. ( 12884437 )
2003
25
Prenatal cortical hyperostosis (Caffey disease). ( 12422848 )
2002
26
Lethal prenatal onset infantile cortical hyperostosis (Caffey disease). ( 11827425 )
2001
27
Recurrent severe infantile cortical hyperostosis (Caffey disease) in siblings. ( 9267903 )
1997
28
Perinatal death in two sibs with infantile cortical hyperostosis (Caffey disease). ( 8588573 )
1995
29
Caffey Disease ( 22855962 )
1993
30
Radiographic, haematological, and biochemical findings in a fetus with Caffey disease. ( 1359527 )
1992
31
Infantile cortical hyperostosis (Caffey disease): ultrastructural and immunohistochemical characterization of the peritrabecular cells. ( 1724929 )
1990
32
Caffey disease responding to high-dose immunoglobulin. ( 3294018 )
1988
33
Case report 363: Infantile cortical hyperostosis (Caffey disease ICH) iliac bones, femora, tibiae and left fibula. ( 3526563 )
1986
34
Prostaglandin synthetase inhibitor in Caffey disease. ( 6808107 )
1982
35
Autosomal dominant inheritance with incomplete penetrance of Caffey disease (infantile cortical hyperostosis). ( 7023758 )
1981
36
Case report 139. Infantile cortical hyperostosis (Caffey disease). ( 7008205 )
1981
37
Letter: Familial Caffey disease. ( 1107501 )
1976
38
Infantile cortical hyperostosis. Caffey disease. ( 795262 )
1976
39
Autosomal dominant inheritance of Caffey disease. ( 4609117 )
1974

Variations for Caffey Disease

UniProtKB/Swiss-Prot genetic disease variations for Caffey Disease:

71
# Symbol AA change Variation ID SNP ID
1 COL1A1 p.Arg1014Cys VAR_033097

ClinVar genetic disease variations for Caffey Disease:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 COL1A1 NM_000088.3(COL1A1): c.3040C> T (p.Arg1014Cys) single nucleotide variant Pathogenic rs72653170 GRCh37 Chromosome 17, 48266269: 48266269
2 A4GALT A4GALT, 42C-T single nucleotide variant Pathogenic
3 COL1A1 NM_000088.3(COL1A1): c.472-1G> C single nucleotide variant Pathogenic rs72667020 GRCh37 Chromosome 17, 48275866: 48275866

Expression for Caffey Disease

Search GEO for disease gene expression data for Caffey Disease.

Pathways for Caffey Disease

GO Terms for Caffey Disease

Cellular components related to Caffey Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.65 A4GALT CD36 COL1A1 FAM20C GALNT3
2 extracellular space GO:0005615 9.63 CD36 CD40LG COL1A1 COL1A2 F3 FAM20C
3 collagen trimer GO:0005581 9.13 CD36 COL1A1 COL1A2
4 collagen type I trimer GO:0005584 8.62 COL1A1 COL1A2

Biological processes related to Caffey Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of immune response GO:0050776 9.58 CD40LG COL1A1 COL1A2
2 skeletal system development GO:0001501 9.5 COL1A1 COL1A2 FAM20C
3 cellular response to amino acid stimulus GO:0071230 9.48 COL1A1 COL1A2
4 blood vessel development GO:0001568 9.46 COL1A1 COL1A2
5 collagen fibril organization GO:0030199 9.43 COL1A1 COL1A2
6 platelet activation GO:0030168 9.43 CD40LG COL1A1 COL1A2
7 positive regulation of interleukin-12 production GO:0032735 9.37 CD36 CD40LG
8 protein heterotrimerization GO:0070208 9.16 COL1A1 COL1A2
9 skin morphogenesis GO:0043589 8.96 COL1A1 COL1A2
10 blood coagulation GO:0007596 8.92 CD36 COL1A1 COL1A2 F3

Molecular functions related to Caffey Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 manganese ion binding GO:0030145 9.16 FAM20C GALNT3
2 protease binding GO:0002020 9.13 COL1A1 COL1A2 F3
3 platelet-derived growth factor binding GO:0048407 8.62 COL1A1 COL1A2

Sources for Caffey Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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