Van Buchem Disease malady

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

Aliases & Classifications for Van Buchem Disease

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Aliases & Descriptions for Van Buchem Disease:

Name: Van Buchem Disease 51 11 47 24 25 53 69 12 49 67
Hyperostosis Corticalis Generalisata 47 24 25 53 69
Hyperphosphatasemia Tarda 47 25 69 26
Sost-Related Sclerosing Bone Dysplasia 11 25 13
Endosteal Hyperostosis Autosomal Recessive 47 69
Sclerosteosis 25 67
Vbch 47 69
Hyperotosis Corticalis Generalisata Familiaris 25
Sost Sclerosing Bone Dysplasia 25
Smith-Lemli-Opitz Syndrome 67


Orphanet epidemiological data:

van buchem disease:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: normal life expectancy


van buchem disease:
Inheritance: autosomal recessive inheritance


External Ids:

OMIM51 239100
Disease Ontology11 DOID:0080036
Orphanet53 ORPHA3416
ICD10 via Orphanet30 M85.2
MedGen36 C0432272
MeSH38 D010009

Summaries for Van Buchem Disease

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Genetics Home Reference:25 SOST-related sclerosing bone dysplasia is a disorder of bone development characterized by excessive bone formation (hyperostosis). As a result of hyperostosis, bones throughout the body are denser and wider than normal, particularly the bones of the skull. Affected individuals typically have an enlarged jaw with misaligned teeth. People with this condition may also have a sunken appearance of the middle of the face (midface hypoplasia), bulging eyes with shallow eye sockets (ocular proptosis), and a prominent forehead. People with this condition often experience headaches because increased thickness of the skull bones increases pressure on the brain. The excessive bone formation seen in this condition seems to occur throughout a person's life, so the skeletal features become more pronounced over time. However, the excessive bone growth may only occur in certain areas.

MalaCards based summary: Van Buchem Disease, also known as hyperostosis corticalis generalisata, is related to sost-related sclerosing bone dysplasias and van buchem disease, type 2, and has symptoms including mandibular prognathia, abnormality of the clavicle and abnormal cortical bone morphology. An important gene associated with Van Buchem Disease is SOST (Sclerostin), and among its related pathways are Regulation of FZD by ubiquitination and Wnt signaling network. Affiliated tissues include skull, bone and eye, and related mouse phenotypes are reproductive system and integument.

Disease Ontology:11 A hyperostosis that has material basis in a mutation in the SOST gene which results in overgrowth of endosteal bone producing dense and wide bones throughout the body especially located in skull.

OMIM:51 Van Buchem disease is an autosomal recessive bone dysplasia characterized by a symmetrically increased thickness of... (239100) more...

UniProtKB/Swiss-Prot:69 Van Buchem disease: VBCH is an autosomal recessive sclerosing bone dysplasia characterized by endosteal hyperostosis of the mandible, skull, ribs, clavicles, and diaphyses of the long bones. Affected patients present a symmetrically increased thickness of bones, most frequently found as an enlarged jawbone, but also an enlargement of the skull, ribs, diaphysis of long bones, as well as tubular bones of hands and feet. The clinical consequence of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurological pain, and, very rarely, blindness as a consequence of optic atrophy. Serum alkaline phosphatase levels are elevated.

Related Diseases for Van Buchem Disease

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Graphical network of the top 20 diseases related to Van Buchem Disease:

Diseases related to van buchem disease

Symptoms for Van Buchem Disease

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Symptoms by clinical synopsis from OMIM:


Clinical features from OMIM:


Human phenotypes related to Van Buchem Disease:

 63 53 (show all 16)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mandibular prognathia63 53 hallmark (90%) Very frequent (99-80%) HP:0000303
2 abnormality of the clavicle63 53 hallmark (90%) Very frequent (99-80%) HP:0000889
3 abnormal cortical bone morphology63 53 hallmark (90%) Very frequent (99-80%) HP:0003103
4 craniofacial hyperostosis63 hallmark (90%) HP:0004493
5 increased bone mineral density63 hallmark (90%) HP:0011001
6 sensorineural hearing impairment63 53 typical (50%) Frequent (79-30%) HP:0000407
7 facial palsy63 53 typical (50%) Frequent (79-30%) HP:0010628
8 hearing impairment63 HP:0000365
9 thickened cortex of long bones63 HP:0000935
10 headache63 HP:0002315
11 elevated alkaline phosphatase63 HP:0003155
12 cranial hyperostosis63 53 Very frequent (99-80%) HP:0004437
13 cranial nerve paralysis63 HP:0006824
14 optic atrophy from cranial nerve compression63 HP:0007958
15 diaphyseal thickening53 Very frequent (99-80%)
16 generalized osteosclerosis53 Very frequent (99-80%)

UMLS symptoms related to Van Buchem Disease:

constipation, seizures, vomiting, unspecified visual loss

Drugs & Therapeutics for Van Buchem Disease

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Van Buchem Disease

Genetic Tests for Van Buchem Disease

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Genetic tests related to Van Buchem Disease:

id Genetic test Affiliating Genes
1 Hyperphosphatasemia Tarda26
2 Van Buchem Disease24 SOST

Anatomical Context for Van Buchem Disease

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MalaCards organs/tissues related to Van Buchem Disease:

Bone, Eye, Brain, Cortex

FMA organs/tissues related to Van Buchem Disease:


Animal Models for Van Buchem Disease or affiliated genes

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MGI Mouse Phenotypes related to Van Buchem Disease:

40 (show all 16)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053898.2COL1A1, GREM1, LRP4, LRP6, NOG, VDR
2MP:00107718.2COL1A1, LRP4, LRP6, MEOX1, NOG, VDR
3MP:00053697.8COL1A1, MEF2A, MEF2C, MEOX1, NOG, VDR
4MP:00053867.5COL1A1, LRP4, LRP5, LRP6, MEF2A, MEF2C
5MP:00053887.3COL1A1, GREM1, LRP4, LRP6, MEF2A, MEF2C
6MP:00053827.1COL1A1, LRP4, LRP5, LRP6, MEF2C, MEOX1
7MP:00053677.1COL1A1, GREM1, LRP4, LRP6, MEF2C, NOG
8MP:00053807.0COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2C
9MP:00028737.0COL1A1, LRP5, LRP6, MEF2A, MEF2C, MEOX1
10MP:00053846.6COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2A
11MP:00053766.5COL1A1, GREM1, LRP4, LRP5, LRP6, MEOX1
12MP:00053716.3COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2C
13MP:00053906.3COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2C
14MP:00107685.9COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2A
15MP:00036315.7COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2A
16MP:00053785.5COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2A

Publications for Van Buchem Disease

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Articles related to Van Buchem Disease:

(show all 20)
Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. (23074140)
A rare cause of facial nerve palsy in children: hyperostosis corticalis generalisata (Van Buchem disease). Three new pediatric cases and a literature review. (22445802)
Sost, ECR5, Mef2C and van Buchem disease. (24049632)
Egill SkallagrA-msson: the first case of Van Buchem disease? (21677924)
Sclerostin in mineralized matrices and van Buchem disease. (19587164)
Case 150: Van Buchem disease (hyperostosis corticalis generalisata). (19789259)
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. (15965026)
Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. (15514891)
Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal. (14671168)
Van Buchem disease: lifetime evolution of radioclinical features. (14520501)
A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. (12116252)
Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. (11836356)
Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. (10330353)
Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. (9463328)
Syringohydromyelia with Van Buchem disease. (9111683)
Facial paralysis at the age of 2 months as a first clinical sign of van Buchem disease (endosteal hyperostosis). (3276528)
Van Buchem disease: surgical treatment of the mandible. (3377422)
The syndromic status of sclerosteosis and van Buchem disease. (6323069)
Van Buchem disease. (199895)
Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations. (198845)

Variations for Van Buchem Disease

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Clinvar genetic disease variations for Van Buchem Disease:

id Gene Variation Type Significance SNP ID Assembly Location
1SOSTNM_025237.2(SOST): c.70C> T (p.Gln24Ter)SNVPathogenicrs387906320GRCh37Chr 17, 41836040: 41836040
2SOSTSOST, IVS1DS, A-T, +3 AND/OR IVS1AS, A-C, -67SNVPathogenicChr na, -1: -1
3SOSTNM_025237.2(SOST): c.372G> A (p.Trp124Ter)SNVPathogenicrs104894644GRCh37Chr 17, 41832980: 41832980
4SOSTNM_025237.2(SOST): c.376C> T (p.Arg126Ter)SNVPathogenicrs104894645GRCh37Chr 17, 41832976: 41832976

Expression for genes affiliated with Van Buchem Disease

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Search GEO for disease gene expression data for Van Buchem Disease.

GO Terms for genes affiliated with Van Buchem Disease

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Cellular components related to Van Buchem Disease according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1Wnt-Frizzled-LRP5/6 complexGO:199085110.0LRP5, LRP6
2Wnt signalosomeGO:19909099.5LRP5, LRP6
3receptor complexGO:00432359.4LRP5, LRP6, VDR

Biological processes related to Van Buchem Disease according to GeneCards Suite gene sharing:

(show all 30)
idNameGO IDScoreTop Affiliating Genes
1Wnt signaling pathway involved in dorsal/ventral axis specificationGO:004433210.5LRP5, LRP6
2negative regulation of protein serine/threonine kinase activityGO:007190110.3LRP5, LRP6
3beta-catenin destruction complex disassemblyGO:190488610.3LRP5, LRP6
4negative regulation of osteoblast differentiationGO:004566810.2LRP5, NOG
5dendrite morphogenesisGO:004881310.2LRP4, MEF2A
6somite developmentGO:006105310.1MEOX1, NOG
7dorsal/ventral pattern formationGO:000995310.1LRP4, NOG
8ureteric bud formationGO:006067610.0GREM1, NOG
9cellular response to parathyroid hormone stimulusGO:007137410.0MEF2C, SOST
10positive regulation of branching involved in ureteric bud morphogenesisGO:009019010.0GREM1, NOG
11response to peptide hormoneGO:00434349.9COL1A1, LRP5, LRP6
12neural crest cell differentiationGO:00140339.9LRP6, MEF2C
13embryonic skeletal system developmentGO:00487069.9COL1A1, NOG
14embryonic digit morphogenesisGO:00427339.8LRP4, LRP5, NOG
15negative regulation of pathway-restricted SMAD protein phosphorylationGO:00603949.8GREM1, NOG
16proximal/distal pattern formationGO:00099549.8GREM1, LRP4
17positive regulation of cardiac muscle cell differentiationGO:20007279.7GREM1, MEF2C
18positive regulation of muscle cell differentiationGO:00511499.7MEF2A, MEF2C
19endochondral ossificationGO:00019589.7COL1A1, MEF2C
20negative regulation of ossificationGO:00302799.6LRP4, MEF2C, SOST
21collagen fibril organizationGO:00301999.6COL1A1, GREM1
22face morphogenesisGO:00603259.5COL1A1, LRP6, NOG
23limb developmentGO:00601739.5GREM1, LRP4, NOG
24negative regulation of BMP signaling pathwayGO:00305149.5GREM1, NOG, SOST
25skeletal system developmentGO:00015019.5COL1A1, NOG, VDR
26Wnt signaling pathwayGO:00160559.1LRP4, LRP5, LRP6, SOST
27osteoblast differentiationGO:00016498.9COL1A1, MEF2C, NOG
28negative regulation of canonical Wnt signaling pathwayGO:00900908.3GREM1, LRP4, LRP6, NOG, SOST
29positive regulation of transcription, DNA-templatedGO:00458937.4COL1A1, GREM1, LRP5, LRP6, MEF2A, MEF2C
30positive regulation of transcription from RNA polymerase II promoterGO:00459446.4GREM1, LRP5, LRP6, MEF2A, MEF2C, MEOX1

Molecular functions related to Van Buchem Disease according to GeneCards Suite gene sharing:

(show all 12)
idNameGO IDScoreTop Affiliating Genes
1coreceptor activity involved in canonical Wnt signaling pathwayGO:190492810.6LRP5, LRP6
2coreceptor activity involved in Wnt signaling pathwayGO:007193610.6LRP5, LRP6
3toxin transporter activityGO:001953410.5LRP5, LRP6
4Wnt-activated receptor activityGO:004281310.5LRP5, LRP6
5apolipoprotein bindingGO:003418510.5LRP4, LRP6
6Wnt-protein bindingGO:001714710.4LRP5, LRP6
7core promoter sequence-specific DNA bindingGO:00010469.8MEF2C, MEOX1
8activating transcription factor bindingGO:00336139.7MEF2A, MEF2C
9HMG box domain bindingGO:00718379.7MEF2C, MEOX1
10transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific bindingGO:00010779.2MEF2A, MEF2C, MEOX1
11sequence-specific DNA bindingGO:00435658.6MEF2A, MEF2C, MEOX1, VDR
12protein bindingGO:00055155.5COL1A1, GREM1, LRP4, LRP5, LRP6, MEF2A

Sources for Van Buchem Disease

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30ICD10 via Orphanet
39MESH via Orphanet
52OMIM via Orphanet
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
68UMLS via Orphanet