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Hyperphosphatasemia tarda(VBCH)

MedGen UID:
98484
Concept ID:
C0432272
Disease or Syndrome
Synonyms: Endosteal hyperostosis autosomal recessive; Hyperostosis Corticalis Generalisata; SOST-Related Sclerosing Bone Dysplasias; van Buchem Disease; VBCH
SNOMED CT: Van Buchem disease (59763006); Hyperphosphatasemia tarda (59763006); Hyperostosis corticalis generalisata (59763006); Leontiasis ossea generalisata (59763006); Hyperphosphatasia tarda (59763006); van Buchem's syndrome (59763006)
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Monarch Initiative: MONDO:0009395
OMIM®: 239100
Orphanet: ORPHA3416

Definition

SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation. The major clinical features of sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Facial distortion due to bossing of the forehead and mandibular overgrowth is seen in nearly all individuals and becomes apparent in early childhood with progression into adulthood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (leading to facial palsy) with other, less common nerve entrapment syndromes including visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensory hearing loss (8th cranial nerve). In sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with sclerosteosis into old age is unusual, but not unprecedented. The manifestations of van Buchem disease are generally milder than sclerosteosis and syndactyly is absent; life span appears to be normal. [from GeneReviews]

Additional descriptions

From OMIM
Van Buchem disease (VBCH) 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).  http://www.omim.org/entry/239100
From MedlinePlus Genetics
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.

Abnormal bone growth can pinch (compress) the cranial nerves, which emerge from the brain and extend to various areas of the head and neck. Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), hearing loss, vision loss, and a sense of smell that is diminished (hyposmia) or completely absent (anosmia). Abnormal bone growth can cause life-threatening complications if it compresses the part of the brain that is connected to the spinal cord (the brainstem).

There are two forms of SOST-related sclerosing bone dysplasia: sclerosteosis and van Buchem disease. The two forms are distinguished by the severity of their symptoms.

Sclerosteosis is the more severe form of the disorder. People with sclerosteosis are often tall and have webbed or fused fingers (syndactyly), most often involving the second and third fingers. The syndactyly is present from birth, while the skeletal features typically appear in early childhood. People with sclerosteosis may also have absent or malformed nails.

Van Buchem disease represents the milder form of the disorder. People with van Buchem disease are typically of average height and do not have syndactyly or nail abnormalities. Affected individuals tend to have less severe cranial nerve compression, resulting in milder neurological features. In people with van Buchem disease, the skeletal features typically appear in childhood or adolescence.  https://medlineplus.gov/genetics/condition/sost-related-sclerosing-bone-dysplasia

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Optic atrophy from cranial nerve compression
MedGen UID:
870320
Concept ID:
C4024763
Pathologic Function
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Cranial hyperostosis
MedGen UID:
318629
Concept ID:
C1832451
Finding
Excessive growth of the bones of cranium, i.e., of the skull.
Thickened cortex of long bones
MedGen UID:
333557
Concept ID:
C1840418
Finding
Abnormal thickening of the cortex of long bones.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyperphosphatasemia tarda

Professional guidelines

PubMed

Leiva-Gea A, Martos Lirio MF, Barreda Bonis AC, Marín Del Barrio S, Heath KE, Marín Reina P, Guillén-Navarro E, Santos Simarro F, Riaño Galán I, Yeste Fernández D, Leiva-Gea I
An Pediatr (Engl Ed) 2022 Dec;97(6):423.e1-423.e11. Epub 2022 Nov 5 doi: 10.1016/j.anpede.2022.10.004. PMID: 36347803
Sawamoto K, Álvarez González JV, Piechnik M, Otero FJ, Couce ML, Suzuki Y, Tomatsu S
Int J Mol Sci 2020 Feb 23;21(4) doi: 10.3390/ijms21041517. PMID: 32102177Free PMC Article
Rossi V, Lee B, Marom R
Curr Opin Pediatr 2019 Dec;31(6):708-715. doi: 10.1097/MOP.0000000000000813. PMID: 31693577Free PMC Article

Recent clinical studies

Etiology

Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
Kozin SH, Zlotolow DA
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Krakow D, Rimoin DL
Genet Med 2010 Jun;12(6):327-41. doi: 10.1097/GIM.0b013e3181daae9b. PMID: 20556869
Savarirayan R, Rimoin DL
Best Pract Res Clin Endocrinol Metab 2002 Sep;16(3):547-60. doi: 10.1053/beem.2002.0210. PMID: 12464233

Diagnosis

Liu A, McEntee J
Pediatr Rev 2019 Aug;40(8):435-438. doi: 10.1542/pir.2017-0340. PMID: 31371639
Silveira MGM, Castellano MVCO, Fuzi CE, Coletta ENAM, Spinosa GN
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Krakow D, Rimoin DL
Genet Med 2010 Jun;12(6):327-41. doi: 10.1097/GIM.0b013e3181daae9b. PMID: 20556869

Therapy

Deguchi M, Tsuji S, Katsura D, Kasahara K, Kimura F, Murakami T
Medicina (Kaunas) 2021 May 10;57(5) doi: 10.3390/medicina57050464. PMID: 34068551Free PMC Article
Rossi V, Lee B, Marom R
Curr Opin Pediatr 2019 Dec;31(6):708-715. doi: 10.1097/MOP.0000000000000813. PMID: 31693577Free PMC Article
Palomo T, Vilaça T, Lazaretti-Castro M
Curr Opin Endocrinol Diabetes Obes 2017 Dec;24(6):381-388. doi: 10.1097/MED.0000000000000367. PMID: 28863000
DiCaprio MR, Enneking WF
J Bone Joint Surg Am 2005 Aug;87(8):1848-64. doi: 10.2106/JBJS.D.02942. PMID: 16085630
Rauch F, Glorieux FH
Lancet 2004 Apr 24;363(9418):1377-85. doi: 10.1016/S0140-6736(04)16051-0. PMID: 15110498

Prognosis

Aparisi Gómez MP, Trisolino G, Sangiorgi L, Guglielmi G, Bazzocchi A
Semin Musculoskelet Radiol 2021 Feb;25(1):22-38. Epub 2021 May 21 doi: 10.1055/s-0041-1723964. PMID: 34020466
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
Wu CC, Econs MJ, DiMeglio LA, Insogna KL, Levine MA, Orchard PJ, Miller WP, Petryk A, Rush ET, Shoback DM, Ward LM, Polgreen LE
J Clin Endocrinol Metab 2017 Sep 1;102(9):3111-3123. doi: 10.1210/jc.2017-01127. PMID: 28655174
Kozin SH, Zlotolow DA
J Hand Surg Am 2015 Oct;40(10):2090-8. Epub 2015 Sep 1 doi: 10.1016/j.jhsa.2015.03.033. PMID: 26341718
Julier C, Nicolino M
Orphanet J Rare Dis 2010 Nov 4;5:29. doi: 10.1186/1750-1172-5-29. PMID: 21050479Free PMC Article

Clinical prediction guides

Turan S
Bone 2023 Feb;167:116615. Epub 2022 Nov 17 doi: 10.1016/j.bone.2022.116615. PMID: 36402365
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
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Pediatr Endocrinol Rev 2013 Jun;10 Suppl 2:389-96. PMID: 23858622
Silve C, Clauser E, Linglart A
Horm Metab Res 2012 Sep;44(10):749-58. Epub 2012 Jul 19 doi: 10.1055/s-0032-1316330. PMID: 22815067

Recent systematic reviews

Li SWS, Roberts E, Hedrich C
RMD Open 2023 Dec 26;9(4) doi: 10.1136/rmdopen-2023-003688. PMID: 38151265Free PMC Article
Bertin H, Moussa MS, Komarova S
Rev Endocr Metab Disord 2023 Dec;24(6):1103-1119. Epub 2023 Aug 26 doi: 10.1007/s11154-023-09832-2. PMID: 37632645
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Adv Ther 2023 Sep;40(9):3639-3680. Epub 2023 Jun 29 doi: 10.1007/s12325-023-02549-3. PMID: 37382866Free PMC Article
Mone F, Mellis R, Gabriel H, Baptiste C, Giordano J, Wapner R, Chitty LS
Am J Obstet Gynecol 2023 Apr;228(4):409-417.e4. Epub 2022 Oct 7 doi: 10.1016/j.ajog.2022.09.045. PMID: 36209938
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Cochrane Database Syst Rev 2016 Oct 19;10(10):CD005088. doi: 10.1002/14651858.CD005088.pub4. PMID: 27760454Free PMC Article

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