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Sclerosteosis

MedGen UID:
120530
•Concept ID:
C0265301
•
Disease or Syndrome
Synonym: Cortical hyperostosis with syndactyly
SNOMED CT: Sclerosteosis (17568006)
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 recessive inheritance (Orphanet)
 
Related genes: SOST, LRP4
 
Monarch Initiative: MONDO:0017838
OMIM®: 269500; 605740
OMIM® Phenotypic series: PS269500
Orphanet: ORPHA3152

Definition

Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001). Genetic Heterogeneity of Sclerosteosis Sclerosteosis-2 (SOST2; 614305) is caused by mutation in the LRP4 gene (604270) on chromosome 11p11. [from OMIM]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Looking for new anabolic treatment from rare diseases of bone formation.
Rossi M, Battafarano G, De Martino V, Scillitani A, Minisola S, Del Fattore A
J Endocrinol 2021 Feb;248(2):R29-R40. doi: 10.1530/JOE-20-0285. PMID: 33258798
From disease to treatment: from rare skeletal disorders to treatments for osteoporosis.
Appelman-Dijkstra NM, Papapoulos SE
Endocrine 2016 Jun;52(3):414-26. Epub 2016 Feb 18 doi: 10.1007/s12020-016-0888-7. PMID: 26892377Free PMC Article
Sclerosing bone dysplasias: neurologic assessment and management.
Hofmeyr LM, Hamersma H
Curr Opin Otolaryngol Head Neck Surg 2004 Oct;12(5):393-7. doi: 10.1097/01.moo.0000134441.84110.9e. PMID: 15377950

Recent clinical studies

Etiology

Crystallization and preliminary X-ray crystallographic analysis of the sclerostin-neutralizing Fab AbD09097.
Boschert V, Muth EM, Knappik A, Frisch C, Mueller TD
Acta Crystallogr F Struct Biol Commun 2015 Apr;71(Pt 4):388-92. Epub 2015 Mar 20 doi: 10.1107/S2053230X1500360X. PMID: 25849496Free PMC Article
Sclerostin and skeletal health.
Sharifi M, Ereifej L, Lewiecki EM
Rev Endocr Metab Disord 2015 Jun;16(2):149-56. doi: 10.1007/s11154-015-9311-6. PMID: 25669441
Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches.
Canalis E
Nat Rev Endocrinol 2013 Oct;9(10):575-83. Epub 2013 Aug 13 doi: 10.1038/nrendo.2013.154. PMID: 23938284
WNT signaling in bone homeostasis and disease: from human mutations to treatments.
Baron R, Kneissel M
Nat Med 2013 Feb;19(2):179-92. Epub 2013 Feb 6 doi: 10.1038/nm.3074. PMID: 23389618
Sclerosteosis in children.
Cremin BJ
Pediatr Radiol 1979 Jul 24;8(3):173-7. doi: 10.1007/BF00973829. PMID: 471562

Diagnosis

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders.
Trajanoska K, Rivadeneira F
Front Endocrinol (Lausanne) 2020;11:556610. Epub 2020 Oct 9 doi: 10.3389/fendo.2020.556610. PMID: 33162933Free PMC Article
Miscellaneous Bone Disorders.
Mughal MZ, Padidela R
Endocr Dev 2015;28:226-246. Epub 2015 Jun 12 doi: 10.1159/000381048. PMID: 26138845
Identification of the disease-causing gene in sclerosteosis--discovery of a novel bone anabolic target?
Balemans W, Van Hul W
J Musculoskelet Neuronal Interact 2004 Jun;4(2):139-42. PMID: 15615113
Sclerosteosis.
Beighton P
J Med Genet 1988 Mar;25(3):200-3. doi: 10.1136/jmg.25.3.200. PMID: 3351908Free PMC Article
Sclerosteosis in South Africa.
Beighton P, Hamersma H
S Afr Med J 1979 May 12;55(20):783-8. PMID: 223247

Therapy

Sclerostin: from bench to bedside.
Tanaka S, Matsumoto T
J Bone Miner Metab 2021 May;39(3):332-340. Epub 2020 Nov 18 doi: 10.1007/s00774-020-01176-0. PMID: 33206222
Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders.
Trajanoska K, Rivadeneira F
Front Endocrinol (Lausanne) 2020;11:556610. Epub 2020 Oct 9 doi: 10.3389/fendo.2020.556610. PMID: 33162933Free PMC Article
Sclerostin and skeletal health.
Sharifi M, Ereifej L, Lewiecki EM
Rev Endocr Metab Disord 2015 Jun;16(2):149-56. doi: 10.1007/s11154-015-9311-6. PMID: 25669441
Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches.
Canalis E
Nat Rev Endocrinol 2013 Oct;9(10):575-83. Epub 2013 Aug 13 doi: 10.1038/nrendo.2013.154. PMID: 23938284
BMP signaling in development and diseases: a pharmacological perspective.
Bandyopadhyay A, Yadav PS, Prashar P
Biochem Pharmacol 2013 Apr 1;85(7):857-64. Epub 2013 Jan 17 doi: 10.1016/j.bcp.2013.01.004. PMID: 23333766

Prognosis

Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third β-Propeller Domain Can Cause Sclerosteosis.
Huybrechts Y, Boudin E, Hendrickx G, Steenackers E, Hamdy N, Mortier G, Martínez Díaz-Guerra G, Bracamonte MS, Appelman-Dijkstra NM, Van Hul W
Genes (Basel) 2021 Dec 28;13(1) doi: 10.3390/genes13010080. PMID: 35052419Free PMC Article
Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders.
Trajanoska K, Rivadeneira F
Front Endocrinol (Lausanne) 2020;11:556610. Epub 2020 Oct 9 doi: 10.3389/fendo.2020.556610. PMID: 33162933Free PMC Article
A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2.
Bukowska-Olech E, Sowińska-Seidler A, Szczałuba K, Jamsheer A
Birth Defects Res 2020 May 15;112(9):652-659. Epub 2020 Apr 14 doi: 10.1002/bdr2.1676. PMID: 32286743
Sclerosteosis in old age.
Barnard AH, Hamersma H, Kretzmar JH, Beighton P
S Afr Med J 1980 Sep 6;58(10):401-3. PMID: 7404164
A review of the osteopetroses.
Beighton P, Horan F, Hamersma H
Postgrad Med J 1977 Aug;53(622):507-16. doi: 10.1136/pgmj.53.622.507. PMID: 335376Free PMC Article

Clinical prediction guides

Novel insights on the effect of sclerostin on bone and other organs.
Dreyer TJ, Keen JA, Wells LM, Roberts SJ
J Endocrinol 2023 May 1;257(2) Epub 2023 Apr 3 doi: 10.1530/JOE-22-0209. PMID: 36802398
Anatomical similarity between the Sost-knockout mouse and sclerosteosis in humans.
Schwarze UY, Dobsak T, Gruber R, Bookstein FL
Anat Rec (Hoboken) 2020 Sep;303(9):2295-2308. Epub 2019 Dec 17 doi: 10.1002/ar.24318. PMID: 31729194Free PMC Article
Role and mechanism of action of sclerostin in bone.
Delgado-Calle J, Sato AY, Bellido T
Bone 2017 Mar;96:29-37. Epub 2016 Oct 12 doi: 10.1016/j.bone.2016.10.007. PMID: 27742498Free PMC Article
Sclerostin: a novel target for intervention in the treatment of osteoporosis.
Lewiecki EM
Discov Med 2011 Oct;12(65):263-73. PMID: 22031665
A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene.
Balemans W, Cleiren E, Siebers U, Horst J, Van Hul W
Bone 2005 Jun;36(6):943-7. doi: 10.1016/j.bone.2005.02.019. PMID: 15869924

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