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X-linked osteoporosis with fractures

MedGen UID:
1674557
•Concept ID:
C5190610
•
Disease or Syndrome
SNOMED CT: X-linked osteoporosis with fractures (782785002)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
•Concept ID:
C1845977
•
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
See: This record
X-linked recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0018315
Orphanet: ORPHA391330

Definition

A rare genetic primary bone dysplasia with decreased bone density disorder with characteristics of childhood-onset osteoporosis associated with recurrent, multiple, osteoporotic, long bone fractures and/or vertebral compression fractures, significant height loss in adulthood, low bone mineral density scores and otherwise no other abnormalities. Heterozygote females may be unaffected or have a milder phenotype. There is evidence the disease can be caused by mutation in the PLS3 gene on chromosome Xq23. [from SNOMEDCT_US]

Professional guidelines

PubMed

Proceedings of the 2023 Santa Fe Bone Symposium: Progress and Controversies in the Management of Patients with Skeletal Diseases.
Lewiecki EM, Bellido T, Bilezikian JP, Brown JP, Farooki A, Kovacs CS, Lee B, Leslie WD, McClung MR, Prasarn ML, Sellmeyer DE
J Clin Densitom 2023 Oct-Dec;26(4):101432. Epub 2023 Oct 14 doi: 10.1016/j.jocd.2023.101432. PMID: 37944445Free PMC Article
Pathogenesis and treatment of osteoporosis in patients with hemophilia.
Lin X, Gao P, Zhang Q, Jiang Y, Wang O, Xia W, Li M
Arch Osteoporos 2023 Jan 4;18(1):17. doi: 10.1007/s11657-022-01203-9. PMID: 36598583Free PMC Article
Identification of a novel splicing mutation and genotype-phenotype correlations in rare PLS3-related childhood-onset osteoporosis.
Wu Z, Feng Z, Zhu X, Dai Z, Min K, Qiu Y, Yi L, Xu L, Zhu Z
Orphanet J Rare Dis 2022 Jun 25;17(1):247. doi: 10.1186/s13023-022-02380-z. PMID: 35752817Free PMC Article

Recent clinical studies

Etiology

Bone fragility and osteoporosis in children and young adults.
Formosa MM, Christou MA, Mäkitie O
J Endocrinol Invest 2024 Feb;47(2):285-298. Epub 2023 Sep 5 doi: 10.1007/s40618-023-02179-0. PMID: 37668887Free PMC Article
Pathogenesis and treatment of osteoporosis in patients with hemophilia.
Lin X, Gao P, Zhang Q, Jiang Y, Wang O, Xia W, Li M
Arch Osteoporos 2023 Jan 4;18(1):17. doi: 10.1007/s11657-022-01203-9. PMID: 36598583Free PMC Article
Familial exudative vitreoretinopathy and related retinopathies.
Gilmour DF
Eye (Lond) 2015 Jan;29(1):1-14. Epub 2014 Oct 17 doi: 10.1038/eye.2014.70. PMID: 25323851Free PMC Article
What is new in genetics and osteogenesis imperfecta classification?
Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B
J Pediatr (Rio J) 2014 Nov-Dec;90(6):536-41. Epub 2014 Jul 18 doi: 10.1016/j.jped.2014.05.003. PMID: 25046257
PLS3 mutations in X-linked osteoporosis with fractures.
van Dijk FS, Zillikens MC, Micha D, Riessland M, Marcelis CL, de Die-Smulders CE, Milbradt J, Franken AA, Harsevoort AJ, Lichtenbelt KD, Pruijs HE, Rubio-Gozalbo ME, Zwertbroek R, Moutaouakil Y, Egthuijsen J, Hammerschmidt M, Bijman R, Semeins CM, Bakker AD, Everts V, Klein-Nulend J, Campos-Obando N, Hofman A, te Meerman GJ, Verkerk AJ, Uitterlinden AG, Maugeri A, Sistermans EA, Waisfisz Q, Meijers-Heijboer H, Wirth B, Simon ME, Pals G
N Engl J Med 2013 Oct 17;369(16):1529-36. Epub 2013 Oct 2 doi: 10.1056/NEJMoa1308223. PMID: 24088043

Diagnosis

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.
Costa A, Martins A, Machado C, Lundberg E, Nilsson O, Wang F, Costantini A, Tournis S, Höppner J, Grasemann C, Mäkitie O
Calcif Tissue Int 2024 Feb;114(2):157-170. Epub 2023 Dec 3 doi: 10.1007/s00223-023-01162-4. PMID: 38043102Free PMC Article
Bone fragility and osteoporosis in children and young adults.
Formosa MM, Christou MA, Mäkitie O
J Endocrinol Invest 2024 Feb;47(2):285-298. Epub 2023 Sep 5 doi: 10.1007/s40618-023-02179-0. PMID: 37668887Free PMC Article
Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.
Oheim R, Tsourdi E, Seefried L, Beller G, Schubach M, Vettorazzi E, Stürznickel J, Rolvien T, Ehmke N, Delsmann A, Genest F, Krüger U, Zemojtel T, Barvencik F, Schinke T, Jakob F, Hofbauer LC, Mundlos S, Kornak U
J Clin Endocrinol Metab 2022 Jun 16;107(7):e3048-e3057. doi: 10.1210/clinem/dgac147. PMID: 35276006Free PMC Article
Mendelian bone fragility disorders.
Robinson ME, Rauch F
Bone 2019 Sep;126:11-17. Epub 2019 Apr 27 doi: 10.1016/j.bone.2019.04.021. PMID: 31039433
PLS3 mutations in X-linked osteoporosis with fractures.
van Dijk FS, Zillikens MC, Micha D, Riessland M, Marcelis CL, de Die-Smulders CE, Milbradt J, Franken AA, Harsevoort AJ, Lichtenbelt KD, Pruijs HE, Rubio-Gozalbo ME, Zwertbroek R, Moutaouakil Y, Egthuijsen J, Hammerschmidt M, Bijman R, Semeins CM, Bakker AD, Everts V, Klein-Nulend J, Campos-Obando N, Hofman A, te Meerman GJ, Verkerk AJ, Uitterlinden AG, Maugeri A, Sistermans EA, Waisfisz Q, Meijers-Heijboer H, Wirth B, Simon ME, Pals G
N Engl J Med 2013 Oct 17;369(16):1529-36. Epub 2013 Oct 2 doi: 10.1056/NEJMoa1308223. PMID: 24088043

Therapy

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.
Costa A, Martins A, Machado C, Lundberg E, Nilsson O, Wang F, Costantini A, Tournis S, Höppner J, Grasemann C, Mäkitie O
Calcif Tissue Int 2024 Feb;114(2):157-170. Epub 2023 Dec 3 doi: 10.1007/s00223-023-01162-4. PMID: 38043102Free PMC Article
Maintenance of bone resorption markers in the low premenopausal range during the year following denosumab discontinuation is associated to bone density preservation. The ReoLaus study.
Liebich G, Lamy O, Aubry-Rozier B, Gonzalez-Rodriguez E
Bone 2023 Jul;172:116764. Epub 2023 Apr 14 doi: 10.1016/j.bone.2023.116764. PMID: 37062514
Pathogenesis and treatment of osteoporosis in patients with hemophilia.
Lin X, Gao P, Zhang Q, Jiang Y, Wang O, Xia W, Li M
Arch Osteoporos 2023 Jan 4;18(1):17. doi: 10.1007/s11657-022-01203-9. PMID: 36598583Free PMC Article
Case report: Clinical characteristics and treatment of secondary osteoporosis induced by X-linked congenital adrenal dysplasia.
Tao X, Xu T, Liu L, Lin X, Zhang Z, Yue H
Front Endocrinol (Lausanne) 2022;13:961322. Epub 2022 Dec 8 doi: 10.3389/fendo.2022.961322. PMID: 36568103Free PMC Article
Identification of a novel splicing mutation and genotype-phenotype correlations in rare PLS3-related childhood-onset osteoporosis.
Wu Z, Feng Z, Zhu X, Dai Z, Min K, Qiu Y, Yi L, Xu L, Zhu Z
Orphanet J Rare Dis 2022 Jun 25;17(1):247. doi: 10.1186/s13023-022-02380-z. PMID: 35752817Free PMC Article

Prognosis

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.
Costa A, Martins A, Machado C, Lundberg E, Nilsson O, Wang F, Costantini A, Tournis S, Höppner J, Grasemann C, Mäkitie O
Calcif Tissue Int 2024 Feb;114(2):157-170. Epub 2023 Dec 3 doi: 10.1007/s00223-023-01162-4. PMID: 38043102Free PMC Article
Case report: Clinical characteristics and treatment of secondary osteoporosis induced by X-linked congenital adrenal dysplasia.
Tao X, Xu T, Liu L, Lin X, Zhang Z, Yue H
Front Endocrinol (Lausanne) 2022;13:961322. Epub 2022 Dec 8 doi: 10.3389/fendo.2022.961322. PMID: 36568103Free PMC Article
Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.
Oheim R, Tsourdi E, Seefried L, Beller G, Schubach M, Vettorazzi E, Stürznickel J, Rolvien T, Ehmke N, Delsmann A, Genest F, Krüger U, Zemojtel T, Barvencik F, Schinke T, Jakob F, Hofbauer LC, Mundlos S, Kornak U
J Clin Endocrinol Metab 2022 Jun 16;107(7):e3048-e3057. doi: 10.1210/clinem/dgac147. PMID: 35276006Free PMC Article
A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family.
Wang L, Bian X, Cheng G, Zhao P, Xiang X, Tian W, Li T, Zhai Q
Ann Hum Genet 2020 Jan;84(1):92-96. Epub 2019 Jul 26 doi: 10.1111/ahg.12344. PMID: 31347706
Novel PLS3 variants in X-linked osteoporosis: Exploring bone material properties.
Balasubramanian M, Fratzl-Zelman N, O'Sullivan R, Bull M, Fa Peel N, Pollitt RC, Jones R, Milne E, Smith K, Roschger P, Klaushofer K, Bishop NJ
Am J Med Genet A 2018 Jul;176(7):1578-1586. Epub 2018 May 7 doi: 10.1002/ajmg.a.38830. PMID: 29736964

Clinical prediction guides

Bone fragility and osteoporosis in children and young adults.
Formosa MM, Christou MA, Mäkitie O
J Endocrinol Invest 2024 Feb;47(2):285-298. Epub 2023 Sep 5 doi: 10.1007/s40618-023-02179-0. PMID: 37668887Free PMC Article
Identification of a novel splicing mutation and genotype-phenotype correlations in rare PLS3-related childhood-onset osteoporosis.
Wu Z, Feng Z, Zhu X, Dai Z, Min K, Qiu Y, Yi L, Xu L, Zhu Z
Orphanet J Rare Dis 2022 Jun 25;17(1):247. doi: 10.1186/s13023-022-02380-z. PMID: 35752817Free PMC Article
Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.
Oheim R, Tsourdi E, Seefried L, Beller G, Schubach M, Vettorazzi E, Stürznickel J, Rolvien T, Ehmke N, Delsmann A, Genest F, Krüger U, Zemojtel T, Barvencik F, Schinke T, Jakob F, Hofbauer LC, Mundlos S, Kornak U
J Clin Endocrinol Metab 2022 Jun 16;107(7):e3048-e3057. doi: 10.1210/clinem/dgac147. PMID: 35276006Free PMC Article
A novel nonsense variant in PLS3 causes X-linked osteoporosis in a Chinese family.
Wang L, Bian X, Cheng G, Zhao P, Xiang X, Tian W, Li T, Zhai Q
Ann Hum Genet 2020 Jan;84(1):92-96. Epub 2019 Jul 26 doi: 10.1111/ahg.12344. PMID: 31347706
A novel splice mutation in PLS3 causes X-linked early onset low-turnover osteoporosis.
Laine CM, Wessman M, Toiviainen-Salo S, Kaunisto MA, Mäyränpää MK, Laine T, Pekkinen M, Kröger H, Välimäki VV, Välimäki MJ, Lehesjoki AE, Mäkitie O
J Bone Miner Res 2015 Mar;30(3):510-8. doi: 10.1002/jbmr.2355. PMID: 25209159

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