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Multiple prenatal fractures

MedGen UID:
377844
Concept ID:
C1853171
Finding
Synonyms: Multiple fractures present at birth; Multiple fractures, present at birth; Numerous multiple fractures present at birth
 
HPO: HP:0005855

Definition

The presence of bone fractures in the prenatal period that are diagnosed at birth or before. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMultiple prenatal fractures

Conditions with this feature

Osteogenesis imperfecta, perinatal lethal
MedGen UID:
75673
Concept ID:
C0268358
Congenital Abnormality
COL1A1/2 osteogenesis imperfecta (COL1A1/2-OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent, wear down, and break easily. COL1A1/2-OI has been classified into four types based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four more common OI types are now referred to as follows: Classic non-deforming OI with blue sclerae (previously OI type I). Perinatally lethal OI (previously OI type II). Progressively deforming OI (previously OI type III). Common variable OI with normal sclerae (previously OI type IV).
Osteogenesis imperfecta type III
MedGen UID:
78664
Concept ID:
C0268362
Disease or Syndrome
COL1A1/2 osteogenesis imperfecta (COL1A1/2-OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent, wear down, and break easily. COL1A1/2-OI has been classified into four types based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four more common OI types are now referred to as follows: Classic non-deforming OI with blue sclerae (previously OI type I). Perinatally lethal OI (previously OI type II). Progressively deforming OI (previously OI type III). Common variable OI with normal sclerae (previously OI type IV).
Osteogenesis imperfecta type 9
MedGen UID:
376720
Concept ID:
C1850169
Disease or Syndrome
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized clinically by bone fragility and increased susceptibility to fractures. Osteogenesis imperfecta type IX (OI9) is a severe autosomal recessive form of the disorder (summary by van Dijk et al., 2009).
Congenital osteogenesis imperfecta-microcephaly-cataracts syndrome
MedGen UID:
337988
Concept ID:
C1850184
Disease or Syndrome
A rare multiple congenital malformations/dysmorphic syndrome characterized by osteogenesis imperfecta with multiple prenatal bone fractures, joint laxity, severe microcephaly, and bilateral cataracts. Additional reported manifestations include dysmorphic facial features (such as blue sclerae, hypertelorism, and low-set ears), lissencephaly, hydrocephalus, and cardiac and genital anomalies. The syndrome is lethal <i>in utero</i> or shortly after birth. There have been no further descriptions in the literature since 1978.
Osteogenesis imperfecta type 7
MedGen UID:
343981
Concept ID:
C1853162
Disease or Syndrome
Osteogenesis imperfecta is a connective tissue disorder characterized by bone fragility and low bone mass. OI type VII is an autosomal recessive form of severe or lethal OI (summary by Barnes et al., 2006).
Osteogenesis imperfecta type 8
MedGen UID:
410075
Concept ID:
C1970458
Disease or Syndrome
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Cabral et al. (2007) described a form of autosomal recessive OI, which they designated OI type VIII, characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses.
Greenberg dysplasia
MedGen UID:
418969
Concept ID:
C2931048
Disease or Syndrome
Greenberg dysplasia (GRBGD), also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia, is a rare autosomal recessive osteochondrodysplasia characterized by gross fetal hydrops, severe shortening of all long bones with a moth-eaten radiographic appearance, platyspondyly, disorganization of chondroosseous calcification, and ectopic ossification centers. It is lethal in utero. Patient fibroblasts show increased levels of cholesta-8,14-dien-3-beta-ol, suggesting a defect of sterol metabolism (summary by Konstantinidou et al., 2008). Herman (2003) reviewed the cholesterol biosynthetic pathway and 6 disorders involving enzyme defects in postsqualene cholesterol biosynthesis: Smith-Lemli-Opitz syndrome (SLOS; 270400), desmosterolosis (602398), X-linked dominant chondrodysplasia punctata (CDPX2; 302960), CHILD syndrome (308050), lathosterolosis (607330), and HEM skeletal dysplasia.
Complex lethal osteochondrodysplasia
MedGen UID:
900688
Concept ID:
C4225162
Disease or Syndrome
Complex lethal osteochondrodysplasia of the Symoens-Barnes-Gistelinck type is characterized by severe skeletal osteopenia, microcephaly, multiple fractures, and congenital anomalies including ascites, pleural effusion, and intracranial ventriculomegaly (Symoens et al., 2015).
Spinal muscular atrophy with congenital bone fractures 2
MedGen UID:
907910
Concept ID:
C4225176
Disease or Syndrome
Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia with fetal hypokinesia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first days or months of life (summary by Knierim et al., 2016). For a discussion of genetic heterogeneity of spinal muscular atrophy with congenital bone fractures, see SMABF1 (616866).
Spinal muscular atrophy with congenital bone fractures 1
MedGen UID:
896011
Concept ID:
C4225177
Disease or Syndrome
Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia with fetal hypokinesia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first days or months of life (summary by Knierim et al., 2016). Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone Fractures See also SMABF2 (616867), caused by mutation in the ASCC1 gene (614215) on chromosome 10q22.
Osteogenesis imperfecta, type 19
MedGen UID:
1648353
Concept ID:
C4746956
Disease or Syndrome
Osteogenesis imperfecta type XIX (OI19) is characterized by prenatal fractures and generalized osteopenia, with severe short stature in adulthood, as well as variable scoliosis and pectal deformity, and marked anterior angulation of the tibia (Lindert et al., 2016).
Osteogenesis imperfecta, type 20
MedGen UID:
1684751
Concept ID:
C5231439
Disease or Syndrome
Osteogenesis imperfecta type XX (OI20) is a progressive deforming bone disorder characterized by osteopenia, skeletal deformity, and both healed and new fractures on radiography. Several patients have died due to respiratory failure (Moosa et al., 2019).
Osteogenesis imperfecta, IIA 22
MedGen UID:
1801631
Concept ID:
C5676943
Disease or Syndrome
Osteogenesis imperfecta comprises a group of connective tissue disorders characterized clinically by bone fragility, low bone mass, and increased susceptibility to fractures. Osteogenesis imperfecta type XXII (OI22) is a severe recessive form of the disease (Dubail et al., 2020).

Professional guidelines

PubMed

Greco PS, Day LJ, Pearlman MD
Obstet Gynecol 2019 Dec;134(6):1343-1357. doi: 10.1097/AOG.0000000000003585. PMID: 31764749
Yeh P, Saeed F, Paramasivam G, Wyatt-Ashmead J, Kumar S
Prenat Diagn 2011 May;31(5):515-8. Epub 2011 Mar 3 doi: 10.1002/pd.2729. PMID: 21370244
Thompson EM
Am J Med Genet 1993 Jan 15;45(2):201-6. doi: 10.1002/ajmg.1320450210. PMID: 8456803

Recent clinical studies

Etiology

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Bone 2023 Mar;168:116644. Epub 2022 Dec 23 doi: 10.1016/j.bone.2022.116644. PMID: 36566820
Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Ariyawatkul T, Worawuthangkul K, Chotigavanichaya C, Kaewpornsawan K, Chalayon O, Eamsobhana P
Int Orthop 2017 Nov;41(11):2361-2364. Epub 2017 Aug 21 doi: 10.1007/s00264-017-3600-5. PMID: 28828634
Hall JG, Aldinger KA, Tanaka KI
Am J Med Genet A 2014 Mar;164A(3):700-30. Epub 2014 Jan 23 doi: 10.1002/ajmg.a.36395. PMID: 24459070
Thompson EM
Am J Med Genet 1993 Jan 15;45(2):201-6. doi: 10.1002/ajmg.1320450210. PMID: 8456803

Diagnosis

Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
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
Greco PS, Day LJ, Pearlman MD
Obstet Gynecol 2019 Dec;134(6):1343-1357. doi: 10.1097/AOG.0000000000003585. PMID: 31764749
Hall JG, Aldinger KA, Tanaka KI
Am J Med Genet A 2014 Mar;164A(3):700-30. Epub 2014 Jan 23 doi: 10.1002/ajmg.a.36395. PMID: 24459070
Thompson EM
Am J Med Genet 1993 Jan 15;45(2):201-6. doi: 10.1002/ajmg.1320450210. PMID: 8456803

Therapy

Sagar RL, Åström E, Chitty LS, Crowe B, David AL, DeVile C, Forsmark A, Franzen V, Hermeren G, Hill M, Johansson M, Lindemans C, Lindgren P, Nijhuis W, Oepkes D, Rehberg M, Sahlin NE, Sakkers R, Semler O, Sundin M, Walther-Jallow L, Verweij EJTJ, Westgren M, Götherström C
BMJ Open 2024 Jun 4;14(6):e079767. doi: 10.1136/bmjopen-2023-079767. PMID: 38834319Free PMC Article
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Gupta N, Gregory SW, Deyle DR, Tebben PJ
J Clin Res Pediatr Endocrinol 2021 Jun 2;13(2):218-224. Epub 2020 Jun 10 doi: 10.4274/jcrpe.galenos.2020.2020.0012. PMID: 32519829Free PMC Article
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Mol Cell Endocrinol 2020 Aug 1;513:110722. Epub 2020 Mar 5 doi: 10.1016/j.mce.2020.110722. PMID: 32147523Free PMC Article
Ariyawatkul T, Worawuthangkul K, Chotigavanichaya C, Kaewpornsawan K, Chalayon O, Eamsobhana P
Int Orthop 2017 Nov;41(11):2361-2364. Epub 2017 Aug 21 doi: 10.1007/s00264-017-3600-5. PMID: 28828634

Prognosis

Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article
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
Finnegan CL, Burke N, Breathnach F, Burke G, McAuliffe F, Morrison JJ, Turner MJ, Dornan S, Higgins JR, Cotter A, Geary M, McParland P, Daly S, Cody F, Dicker P, Smyth S, Tully E, Malone FD
Am J Obstet Gynecol MFM 2019 Aug;1(3):100029. Epub 2019 Aug 7 doi: 10.1016/j.ajogmf.2019.100029. PMID: 33345793
Yeh P, Saeed F, Paramasivam G, Wyatt-Ashmead J, Kumar S
Prenat Diagn 2011 May;31(5):515-8. Epub 2011 Mar 3 doi: 10.1002/pd.2729. PMID: 21370244

Clinical prediction guides

Senturk L, Gulec C, Sarac Sivrikoz T, Kayserili H, Kalelioglu IH, Avci S, Has R, Coucke P, Kalayci T, Wollnik B, Karaman B, Toksoy G, Symoens S, Yigit G, Yuksel A, Basaran S, Tuysuz B, Altunoglu U, Uyguner ZO
Fetal Diagn Ther 2024;51(3):285-299. Epub 2024 Feb 12 doi: 10.1159/000536324. PMID: 38346409
Yang M, Yin H, Zhen D, Ding Y, Wang Y, Sun L, He F, Tang X
Bone 2023 Mar;168:116644. Epub 2022 Dec 23 doi: 10.1016/j.bone.2022.116644. PMID: 36566820
Tran CT, Smet ME, Forsey J, Zankl A, Nayyar R
Fetal Diagn Ther 2022;49(11-12):479-485. Epub 2022 Dec 7 doi: 10.1159/000527594. PMID: 36476632
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
Yeh P, Saeed F, Paramasivam G, Wyatt-Ashmead J, Kumar S
Prenat Diagn 2011 May;31(5):515-8. Epub 2011 Mar 3 doi: 10.1002/pd.2729. PMID: 21370244

Recent systematic reviews

Warnier H, Barrea C, Bethlen S, Schrouff I, Harvengt J
Orphanet J Rare Dis 2022 Apr 23;17(1):174. doi: 10.1186/s13023-022-02323-8. PMID: 35461249Free PMC Article

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