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Osteogenesis imperfecta type I(OI1)

MedGen UID:
9799
Concept ID:
C0023931
Disease or Syndrome
Synonyms: Classic Non-deforming Osteogenesis Imperfecta with Blue Sclerae; Lobstein disease; Lobstein's Disease; OI type 1; OI type 1A; OI, TYPE I; OI1; Osteogenesis imperfecta tarda; Osteogenesis imperfecta type 1; Osteogenesis imperfecta type 1 with dentinogenesis imperfecta; Osteogenesis imperfecta type 1A; Osteogenesis imperfecta with blue sclerae; Osteogenesis imperfecta with opalescent teeth
SNOMED CT: Osteogenesis imperfecta type I (385482004); van de Hoeve syndrome (385482004)
Modes of inheritance:
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.
 
Gene (location): COL1A1 (17q21.33)
 
Monarch Initiative: MONDO:0008146
OMIM®: 166200
Orphanet: ORPHA216796

Disease characteristics

Excerpted from the GeneReview: COL1A1/2 Osteogenesis Imperfecta
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). [from GeneReviews]
Authors:
Robert D Steiner  |  Donald Basel   view full author information

Additional descriptions

From OMIM
Osteogenesis imperfecta type I (OI1) is a dominantly inherited, generalized connective tissue disorder characterized mainly by bone fragility and blue sclerae. In most cases, 'functional null' alleles of COL1A1 on chromosome 17 or COL1A2 on chromosome 7 lead to reduced amounts of normal collagen I.  http://www.omim.org/entry/166200
From MedlinePlus Genetics
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break (fracture) easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.

There are at least 19 recognized forms of osteogenesis imperfecta, designated type I through type XIX. Several types are distinguished by their signs and symptoms, although their characteristic features overlap. Increasingly, genetic causes are used to define rarer forms of osteogenesis imperfecta. Type I (also known as classic non-deforming osteogenesis imperfecta with blue sclerae) is the mildest form of osteogenesis imperfecta. Type II (also known as perinatally lethal osteogenesis imperfecta) is the most severe. Other types of this condition, including types III (progressively deforming osteogenesis imperfecta) and IV (common variable osteogenesis imperfecta with normal sclerae), have signs and symptoms that fall somewhere between these two extremes.

The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma, such as falling while learning to walk. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and about half develop hearing loss in adulthood. Unlike more severely affected individuals, people with type I are usually of normal or near normal height.

Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that are present at birth and result from little or no trauma. Additional features of these types can include blue sclerae of the eyes, short stature, curvature of the spine (scoliosis), joint deformities (contractures), hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. Mobility can be reduced in affected individuals, and some may use a walker or wheelchair. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities may have life-threatening problems with breathing and can die shortly after birth.  https://medlineplus.gov/genetics/condition/osteogenesis-imperfecta

Clinical features

From HPO
Aortic aneurysm
MedGen UID:
362
Concept ID:
C0003486
Disease or Syndrome
Aortic dilatation refers to a dimension that is greater than the 95th percentile for the normal person age, sex and body size. In contrast, an aneurysm is defined as a localized dilation of the aorta that is more than 150 percent of predicted (ratio of observed to expected diameter 1.5 or more). Aneurysm should be distinguished from ectasia, which represents a diffuse dilation of the aorta less than 50 percent of normal aorta diameter.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Growth abnormality
MedGen UID:
808205
Concept ID:
C0262361
Finding
Otosclerosis
MedGen UID:
10508
Concept ID:
C0029899
Disease or Syndrome
Clinical otosclerosis, the single most common cause of hearing impairment, is characterized by isolated endochondral bone sclerosis of the labyrinthine capsule. Otosclerotic foci invade the stapediovestibular joint (oval window) and interfere with free motion of the stapes. Mean age of onset is in the third decade and 90% of affected persons are under 50 years of age at the time of diagnosis. Approximately 10% of affected persons develop profound sensorineural hearing loss across all frequencies (summary by Tomek et al., 1998). Genetic Heterogeneity of Otosclerosis The locus associated with otosclerosis-1 (OTSC1) has been mapped to chromosome 15q26.1. Other loci associated with otosclerosis include OTSC2 (605727) on chromosome 7q; OTSC3 (608244) on chromosome 6p; OTSC4 (611571) on chromosome 16q; OTSC5 (608787) on chromosome 3q22-q24; OTSC7 (611572) on chromosome 6q13; OTSC8 (612096) on chromosome 9p13.1-q21.11; and OTSC10 (615589) on chromosome 1q41-q44. OTSC11 (620576) is caused by mutation in the FOXL1 gene (603252) on chromosome 16q24. The symbols OTSC6 and OTSC9 were reserved by the HUGO Gene Nomenclature Committee on January 30, 2003 and February 10, 2009, respectively, for as yet unpublished loci for otosclerosis.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Dentinogenesis imperfecta
MedGen UID:
8313
Concept ID:
C0011436
Congenital Abnormality
Developmental dysplasia of dentin.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Finger joint hypermobility
MedGen UID:
154359
Concept ID:
C0574974
Finding
Increased susceptibility to fractures
MedGen UID:
234655
Concept ID:
C1390474
Finding
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.
Biconcave flattened vertebrae
MedGen UID:
318956
Concept ID:
C1833753
Finding
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Cozzolino M, Perelli F, Maggio L, Coccia ME, Quaranta M, Gizzo S, Mecacci F
Arch Gynecol Obstet 2016 Jun;293(6):1153-9. Epub 2016 Jan 18 doi: 10.1007/s00404-016-4012-2. PMID: 26781260
Antoniazzi F, Bertoldo F, Mottes M, Valli M, Sirpresi S, Zamboni G, Valentini R, Tató L
J Pediatr 1996 Sep;129(3):432-9. doi: 10.1016/s0022-3476(96)70077-x. PMID: 8804334

Curated

Orphanet Emergency Guidelines: Osteogenesis imperfecta (OI)

Recent clinical studies

Etiology

Coussens M, Lapauw B, Verroken C, Goemaere S, De Wandele I, Malfait F, Banica T, Calders P
J Bone Miner Res 2022 Dec;37(12):2456-2465. Epub 2022 Nov 5 doi: 10.1002/jbmr.4722. PMID: 36239015
Jakubowska-Pietkiewicz E, Maćkowska A, Nowicki J, Woźniak E, Jakub N
BMC Pediatr 2022 Oct 6;22(1):577. doi: 10.1186/s12887-022-03621-7. PMID: 36203124Free PMC Article
Garman CR, Graf A, Krzak J, Caudill A, Smith P, Harris G
J Pediatr Orthop 2019 Sep;39(8):e641-e646. doi: 10.1097/BPO.0000000000001062. PMID: 31393309
Pouliot-Laforte A, Lemay M, Rauch F, Veilleux LN
Arch Phys Med Rehabil 2017 Oct;98(10):1948-1954. Epub 2017 Apr 19 doi: 10.1016/j.apmr.2017.03.018. PMID: 28433416
Cozzolino M, Perelli F, Maggio L, Coccia ME, Quaranta M, Gizzo S, Mecacci F
Arch Gynecol Obstet 2016 Jun;293(6):1153-9. Epub 2016 Jan 18 doi: 10.1007/s00404-016-4012-2. PMID: 26781260

Diagnosis

Niu Z, Lai Y, Zhou W, Liu L, Tan S, He G, Li J, Tang F, Su Y, Xu Y, Liu L, Xie L, Fang Q, Tang A
Mol Genet Genomic Med 2022 Sep;10(9):e2019. Epub 2022 Jul 19 doi: 10.1002/mgg3.2019. PMID: 35855543Free PMC Article
Liu L, Sun L, Chen Y, Wang M, Yu C, Huang Y, Zhao S, Du H, Chen S, Fan X, Tian W, Wu Z; Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group, Qiu G, Zhang TJ, Wu N
Orphanet J Rare Dis 2022 Mar 28;17(1):139. doi: 10.1186/s13023-022-02293-x. PMID: 35346302Free PMC Article
Garman CR, Graf A, Krzak J, Caudill A, Smith P, Harris G
J Pediatr Orthop 2019 Sep;39(8):e641-e646. doi: 10.1097/BPO.0000000000001062. PMID: 31393309
Hoefele J, Mayer K, Marschall C, Alberer M, Klein HG, Kirschstein M
World J Pediatr 2016 Nov;12(4):501-503. Epub 2016 Apr 8 doi: 10.1007/s12519-016-0014-1. PMID: 27059743
Cozzolino M, Perelli F, Maggio L, Coccia ME, Quaranta M, Gizzo S, Mecacci F
Arch Gynecol Obstet 2016 Jun;293(6):1153-9. Epub 2016 Jan 18 doi: 10.1007/s00404-016-4012-2. PMID: 26781260

Therapy

Jakubowska-Pietkiewicz E, Maćkowska A, Nowicki J, Woźniak E, Jakub N
BMC Pediatr 2022 Oct 6;22(1):577. doi: 10.1186/s12887-022-03621-7. PMID: 36203124Free PMC Article
Rothschild L, Goeller JK, Voronov P, Barabanova A, Smith P
Paediatr Anaesth 2018 Nov;28(11):1050-1058. Epub 2018 Oct 8 doi: 10.1111/pan.13504. PMID: 30295359
Gatti D, Rossini M, Viapiana O, Povino MR, Liuzza S, Fracassi E, Idolazzi L, Adami S
Calcif Tissue Int 2013 Nov;93(5):448-52. Epub 2013 Aug 2 doi: 10.1007/s00223-013-9770-2. PMID: 23907723
Bradbury LA, Barlow S, Geoghegan F, Hannon RA, Stuckey SL, Wass JA, Russell RG, Brown MA, Duncan EL
Osteoporos Int 2012 Jan;23(1):285-94. Epub 2011 Jul 8 doi: 10.1007/s00198-011-1658-2. PMID: 21739105
Garretsen TJ, Cremers CW
Ann N Y Acad Sci 1991;630:240-8. doi: 10.1111/j.1749-6632.1991.tb19594.x. PMID: 1952595

Prognosis

Albert C, Jameson J, Toth JM, Smith P, Harris G
Clin Biomech (Bristol, Avon) 2013 Jan;28(1):110-6. Epub 2012 Nov 7 doi: 10.1016/j.clinbiomech.2012.10.003. PMID: 23141422
Bradbury LA, Barlow S, Geoghegan F, Hannon RA, Stuckey SL, Wass JA, Russell RG, Brown MA, Duncan EL
Osteoporos Int 2012 Jan;23(1):285-94. Epub 2011 Jul 8 doi: 10.1007/s00198-011-1658-2. PMID: 21739105
Pollitt R, McMahon R, Nunn J, Bamford R, Afifi A, Bishop N, Dalton A
Hum Mutat 2006 Jul;27(7):716. doi: 10.1002/humu.9430. PMID: 16786509
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Willing MC, Pruchno CJ, Byers PH
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Clinical prediction guides

Garman CR, Graf A, Krzak J, Caudill A, Smith P, Harris G
J Pediatr Orthop 2019 Sep;39(8):e641-e646. doi: 10.1097/BPO.0000000000001062. PMID: 31393309
Hoefele J, Mayer K, Marschall C, Alberer M, Klein HG, Kirschstein M
World J Pediatr 2016 Nov;12(4):501-503. Epub 2016 Apr 8 doi: 10.1007/s12519-016-0014-1. PMID: 27059743
Bardai G, Lemyre E, Moffatt P, Palomo T, Glorieux FH, Tung J, Ward L, Rauch F
Calcif Tissue Int 2016 Jan;98(1):76-84. doi: 10.1007/s00223-015-0066-6. PMID: 26478226
Gatti D, Rossini M, Viapiana O, Povino MR, Liuzza S, Fracassi E, Idolazzi L, Adami S
Calcif Tissue Int 2013 Nov;93(5):448-52. Epub 2013 Aug 2 doi: 10.1007/s00223-013-9770-2. PMID: 23907723
Willing MC, Pruchno CJ, Byers PH
Am J Med Genet 1993 Jan 15;45(2):223-7. doi: 10.1002/ajmg.1320450214. PMID: 8456806

Recent systematic reviews

Gug C, Caba L, Mozos I, Stoian D, Atasie D, Gug M, Gorduza EV
Gene 2020 May 30;741:144565. Epub 2020 Mar 10 doi: 10.1016/j.gene.2020.144565. PMID: 32165296

Supplemental Content

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    • PubMed
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • Orphanet, 2008
      Orphanet Emergency Guidelines: Osteogenesis imperfecta (OI)

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