MCID: VNB005
MIFTS: 46

Van Buchem Disease

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

Aliases & Classifications for Van Buchem Disease

MalaCards integrated aliases for Van Buchem Disease:

Name: Van Buchem Disease 54 12 50 24 25 56 71 13 52 69
Hyperostosis Corticalis Generalisata 50 24 25 56 71
Hyperphosphatasemia Tarda 50 25 56 71 29
Sost-Related Sclerosing Bone Dysplasia 12 25 14
Endosteal Hyperostosis Autosomal Recessive 50 71
Sclerosteosis 25 69
Vbch 50 71
Hyperotosis Corticalis Generalisata Familiaris 25
Sost Sclerosing Bone Dysplasia 25
Smith-Lemli-Opitz Syndrome 69

Characteristics:

Orphanet epidemiological data:

56
hyperostosis corticalis generalisata
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal recessive


HPO:

32
van buchem disease:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 239100
Disease Ontology 12 DOID:0080036
Orphanet 56 ORPHA3416
UMLS via Orphanet 70 C0432272
ICD10 via Orphanet 34 M85.2
MedGen 40 C0432272
MeSH 42 D010009

Summaries for Van Buchem Disease

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 sensorineural hearing impairment, facial palsy and cranial hyperostosis. An important gene associated with Van Buchem Disease is SOST (Sclerostin), and among its related pathways/superpathways are Wnt Signaling Pathway and Pluripotency and Transcription_Role of VDR in regulation of genes involved in osteoporosis. Affiliated tissues include bone, eye and brain, and related phenotypes are growth/size/body region and limbs/digits/tail

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 3416disease definitionhyperostosis corticalis generalisata, also known as van buchem disease, is a rare craniotubular hyperostosis characterized by hyperostosis of the skull, mandible, clavicles, ribs and diaphyses of the long bones, as well as the tubular bones of the hands and feet. clinical manifestations include increased skull thickness with cranial nerve entrapment causing inconsistent cranial nerve palsies.visit the orphanet disease page for more resources. last updated: 3/30/2016

UniProtKB/Swiss-Prot : 71 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.

OMIM : 54
Van Buchem disease is an autosomal recessive bone dysplasia characterized by 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, resulting in increased cortical bone density. The clinical consequences of increased thickness of the skull include facial nerve palsy causing hearing loss, visual problems, neurologic pain, and very rarely, blindness resulting from optic atrophy. Bone anomalies appear in the first decade of life and progress with age (summary by Wergedal et al., 2003). (239100)

Disease Ontology : 12 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.

Related Diseases for Van Buchem Disease

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



Diseases related to Van Buchem Disease

Symptoms & Phenotypes for Van Buchem Disease

Symptoms via clinical synopsis from OMIM:

54

Ears:
hearing loss

Neuro:
headaches
cranial nerve palsy

Radiology:
thickened cortex of long bones

Lab:
hyperphosphatasemia

Skel:
osteosclerosis

Head:
cranial hyperostosis

Eyes:
optic atrophy from cranial nerve compression


Clinical features from OMIM:

239100

Human phenotypes related to Van Buchem Disease:

56 32 (show all 15)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sensorineural hearing impairment 56 32 frequent (33%) Frequent (79-30%) HP:0000407
2 facial palsy 56 32 frequent (33%) Frequent (79-30%) HP:0010628
3 cranial hyperostosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0004437
4 diaphyseal thickening 56 32 hallmark (90%) Very frequent (99-80%) HP:0005019
5 mandibular prognathia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000303
6 abnormal cortical bone morphology 56 32 hallmark (90%) Very frequent (99-80%) HP:0003103
7 generalized osteosclerosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0005789
8 abnormality of the clavicle 56 32 hallmark (90%) Very frequent (99-80%) HP:0000889
9 headache 32 HP:0002315
10 hearing impairment 32 HP:0000365
11 elevated alkaline phosphatase 32 HP:0003155
12 cranial nerve paralysis 32 HP:0006824
13 thickened cortex of long bones 32 HP:0000935
14 increased bone mineral density 32 HP:0011001
15 optic atrophy from cranial nerve compression 32 HP:0007958

UMLS symptoms related to Van Buchem Disease:


constipation, seizures, vomiting, unspecified visual loss

MGI Mouse Phenotypes related to Van Buchem Disease:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.87 COL1A1 LRP4 LRP5 MEF2A MEOX1 SOST
2 limbs/digits/tail MP:0005371 9.8 COL1A1 KREMEN1 LRP4 LRP5 MEOX1 SOST
3 craniofacial MP:0005382 9.77 COL1A1 LRP4 LRP5 MEOX1 VDR
4 nervous system MP:0003631 9.63 COL1A1 LRP4 LRP5 MEF2A MEOX1 VDR
5 normal MP:0002873 9.43 MEF2A MEOX1 SOST COL1A1 KREMEN1 LRP5
6 skeleton MP:0005390 9.17 COL1A1 KREMEN1 LRP4 LRP5 MEOX1 SOST

Drugs & Therapeutics for Van Buchem Disease

Search Clinical Trials , NIH Clinical Center for Van Buchem Disease

Genetic Tests for Van Buchem Disease

Genetic tests related to Van Buchem Disease:

id Genetic test Affiliating Genes
1 Hyperphosphatasemia Tarda 29
2 Van Buchem Disease 24 SOST

Anatomical Context for Van Buchem Disease

MalaCards organs/tissues related to Van Buchem Disease:

39
Bone, Eye, Brain, Cortex

Publications for Van Buchem Disease

Articles related to Van Buchem Disease:

(show all 20)
id Title Authors Year
1
Van Buchem disease: clinical, biochemical, and densitometric features of patients and disease carriers. ( 23074140 )
2013
2
A rare cause of facial nerve palsy in children: hyperostosis corticalis generalisata (Van Buchem disease). Three new pediatric cases and a literature review. ( 22445802 )
2012
3
Sost, ECR5, Mef2C and van Buchem disease. ( 24049632 )
2012
4
Egill SkallagrA-msson: the first case of Van Buchem disease? ( 21677924 )
2011
5
Case 150: Van Buchem disease (hyperostosis corticalis generalisata). ( 19789259 )
2009
6
Sclerostin in mineralized matrices and van Buchem disease. ( 19587164 )
2009
7
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. ( 15965026 )
2005
8
Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. ( 15514891 )
2004
9
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 )
2003
10
Van Buchem disease: lifetime evolution of radioclinical features. ( 14520501 )
2003
11
A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. ( 12116252 )
2002
12
Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. ( 11836356 )
2002
13
Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. ( 10330353 )
1999
14
Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. ( 9463328 )
1998
15
Syringohydromyelia with Van Buchem disease. ( 9111683 )
1997
16
Facial paralysis at the age of 2 months as a first clinical sign of van Buchem disease (endosteal hyperostosis). ( 3276528 )
1988
17
Van Buchem disease: surgical treatment of the mandible. ( 3377422 )
1988
18
The syndromic status of sclerosteosis and van Buchem disease. ( 6323069 )
1984
19
Van Buchem disease. ( 199895 )
1977
20
Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations. ( 198845 )
1977

Variations for Van Buchem Disease

ClinVar genetic disease variations for Van Buchem Disease:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SOST NM_025237.2(SOST): c.70C> T (p.Gln24Ter) single nucleotide variant Pathogenic rs387906320 GRCh37 Chromosome 17, 41836040: 41836040
2 SOST SOST, IVS1DS, A-T, +3 AND/OR IVS1AS, A-C, -67 single nucleotide variant Pathogenic
3 SOST NM_025237.2(SOST): c.372G> A (p.Trp124Ter) single nucleotide variant Pathogenic rs104894644 GRCh37 Chromosome 17, 41832980: 41832980
4 SOST NM_025237.2(SOST): c.376C> T (p.Arg126Ter) single nucleotide variant Pathogenic rs104894645 GRCh37 Chromosome 17, 41832976: 41832976

Expression for Van Buchem Disease

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

Pathways for Van Buchem Disease

GO Terms for Van Buchem Disease

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

id Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.8 LRP4 LRP5 VDR

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

(show all 14)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription from RNA polymerase II promoter GO:0045944 9.83 LRP5 MEF2A MEOX1 VDR
2 multicellular organism development GO:0007275 9.72 LRP4 LRP5 MEF2A MEOX1 VDR
3 positive regulation of transcription, DNA-templated GO:0045893 9.71 COL1A1 LRP5 MEF2A SOST
4 ossification GO:0001503 9.54 COL1A1 SOST
5 negative regulation of canonical Wnt signaling pathway GO:0090090 9.54 KREMEN1 LRP4 SOST
6 response to mechanical stimulus GO:0009612 9.51 COL1A1 SOST
7 embryonic digit morphogenesis GO:0042733 9.49 LRP4 LRP5
8 response to peptide hormone GO:0043434 9.48 COL1A1 LRP5
9 dendrite morphogenesis GO:0048813 9.46 LRP4 MEF2A
10 Wnt signaling pathway GO:0016055 9.46 KREMEN1 LRP4 LRP5 SOST
11 limb development GO:0060173 9.43 KREMEN1 LRP4
12 Wnt signaling pathway involved in dorsal/ventral axis specification GO:0044332 9.26 LRP4 LRP5
13 regulation of canonical Wnt signaling pathway GO:0060828 9.13 KREMEN1 LRP4 LRP5
14 negative regulation of ossification GO:0030279 8.8 KREMEN1 LRP4 SOST

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

id Name GO ID Score Top Affiliating Genes
1 Wnt-protein binding GO:0017147 8.96 LRP4 LRP5
2 Wnt-activated receptor activity GO:0042813 8.62 LRP4 LRP5

Sources for Van Buchem Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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