U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from Gene

Osteogenesis imperfecta type 8(OI8)

MedGen UID:
410075
Concept ID:
C1970458
Disease or Syndrome
Synonyms: LEPRE1-Related Osteogenesis Imperfecta; OI type VIII; OI8; Osteogenesis Imperfecta Type VIII
 
Gene (location): P3H1 (1p34.2)
 
Monarch Initiative: MONDO:0012581
OMIM®: 610915

Definition

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. [from OMIM]

Additional description

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
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Femoral retroversion
MedGen UID:
375866
Concept ID:
C1846339
Congenital Abnormality
An abnormal backward rotation of the hip relative to the knee such that the hips are externally rotated with the foot pointed outward instead of straight ahead (out-toeing).
Radial bowing
MedGen UID:
347136
Concept ID:
C1859399
Anatomical Abnormality
A bending or abnormal curvature of the radius.
Disproportionate short-limb short stature
MedGen UID:
342370
Concept ID:
C1849937
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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).
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Barrel-shaped chest
MedGen UID:
120497
Concept ID:
C0264172
Finding
A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Decreased skull ossification
MedGen UID:
609330
Concept ID:
C0432073
Congenital Abnormality
A reduction in the magnitude or amount of ossification of the skull.
Slender long bone
MedGen UID:
331446
Concept ID:
C1833144
Finding
Reduced diameter of a long bone.
Decreased calvarial ossification
MedGen UID:
322270
Concept ID:
C1833762
Finding
Abnormal reduction in ossification of the calvaria (roof of the skull consisting of the frontal bone, parietal bones, temporal bones, and occipital bone).
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
Multiple prenatal fractures
MedGen UID:
377844
Concept ID:
C1853171
Finding
The presence of bone fractures in the prenatal period that are diagnosed at birth or before.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Type 1 collagen overmodification
MedGen UID:
370919
Concept ID:
C1970463
Finding
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.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Professional guidelines

PubMed

Lin X, Hu J, Zhou B, Zhang Q, Jiang Y, Wang O, Xia W, Xing X, Li M
J Endocrinol Invest 2024 Jan;47(1):67-77. Epub 2023 Jun 4 doi: 10.1007/s40618-023-02123-2. PMID: 37270749Free PMC Article
Lindahl K, Åström E, Rubin CJ, Grigelioniene G, Malmgren B, Ljunggren Ö, Kindmark A
Eur J Hum Genet 2015 Aug;23(8):1042-50. Epub 2015 May 6 doi: 10.1038/ejhg.2015.81. PMID: 25944380Free PMC Article
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292

Recent clinical studies

Etiology

Claeys L, Storoni S, Eekhoff M, Elting M, Wisse L, Pals G, Bravenboer N, Maugeri A, Micha D
Hum Genet 2021 Aug;140(8):1121-1141. Epub 2021 Jun 24 doi: 10.1007/s00439-021-02302-2. PMID: 34169326Free PMC Article
Taqi D, Moussa H, Schwinghamer T, Vieira AR, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC
Bone 2021 Sep;150:116011. Epub 2021 May 18 doi: 10.1016/j.bone.2021.116011. PMID: 34020077
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292
Martínez-Morillo M, Grados D, Holgado S
Reumatol Clin 2012 Mar-Apr;8(2):93-7. Epub 2011 Aug 6 doi: 10.1016/j.reuma.2011.05.011. PMID: 22089064
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article

Diagnosis

Lin X, Hu J, Zhou B, Zhang Q, Jiang Y, Wang O, Xia W, Xing X, Li M
J Endocrinol Invest 2024 Jan;47(1):67-77. Epub 2023 Jun 4 doi: 10.1007/s40618-023-02123-2. PMID: 37270749Free PMC Article
Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292
Martínez-Morillo M, Grados D, Holgado S
Reumatol Clin 2012 Mar-Apr;8(2):93-7. Epub 2011 Aug 6 doi: 10.1016/j.reuma.2011.05.011. PMID: 22089064
Barron MJ, McDonnell ST, Mackie I, Dixon MJ
Orphanet J Rare Dis 2008 Nov 20;3:31. doi: 10.1186/1750-1172-3-31. PMID: 19021896Free PMC Article

Therapy

Song IW, Nagamani SC, Nguyen D, Grafe I, Sutton VR, Gannon FH, Munivez E, Jiang MM, Tran A, Wallace M, Esposito P, Musaad S, Strudthoff E, McGuire S, Thornton M, Shenava V, Rosenfeld S, Huang S, Shypailo R, Orwoll E, Lee B
J Clin Invest 2022 Apr 1;132(7) doi: 10.1172/JCI152571. PMID: 35113812Free PMC Article
Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Trejo P, Palomo T, Montpetit K, Fassier F, Sato A, Glorieux FH, Rauch F
Osteoporos Int 2017 Oct;28(10):2975-2983. Epub 2017 Jul 9 doi: 10.1007/s00198-017-4141-x. PMID: 28689307
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292
Martínez-Morillo M, Grados D, Holgado S
Reumatol Clin 2012 Mar-Apr;8(2):93-7. Epub 2011 Aug 6 doi: 10.1016/j.reuma.2011.05.011. PMID: 22089064

Prognosis

Lin X, Hu J, Zhou B, Zhang Q, Jiang Y, Wang O, Xia W, Xing X, Li M
J Endocrinol Invest 2024 Jan;47(1):67-77. Epub 2023 Jun 4 doi: 10.1007/s40618-023-02123-2. PMID: 37270749Free PMC Article
Claeys L, Storoni S, Eekhoff M, Elting M, Wisse L, Pals G, Bravenboer N, Maugeri A, Micha D
Hum Genet 2021 Aug;140(8):1121-1141. Epub 2021 Jun 24 doi: 10.1007/s00439-021-02302-2. PMID: 34169326Free PMC Article
Trejo P, Palomo T, Montpetit K, Fassier F, Sato A, Glorieux FH, Rauch F
Osteoporos Int 2017 Oct;28(10):2975-2983. Epub 2017 Jul 9 doi: 10.1007/s00198-017-4141-x. PMID: 28689307
Lindahl K, Åström E, Rubin CJ, Grigelioniene G, Malmgren B, Ljunggren Ö, Kindmark A
Eur J Hum Genet 2015 Aug;23(8):1042-50. Epub 2015 May 6 doi: 10.1038/ejhg.2015.81. PMID: 25944380Free PMC Article
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292

Clinical prediction guides

Lin X, Hu J, Zhou B, Zhang Q, Jiang Y, Wang O, Xia W, Xing X, Li M
J Endocrinol Invest 2024 Jan;47(1):67-77. Epub 2023 Jun 4 doi: 10.1007/s40618-023-02123-2. PMID: 37270749Free PMC Article
Claeys L, Storoni S, Eekhoff M, Elting M, Wisse L, Pals G, Bravenboer N, Maugeri A, Micha D
Hum Genet 2021 Aug;140(8):1121-1141. Epub 2021 Jun 24 doi: 10.1007/s00439-021-02302-2. PMID: 34169326Free PMC Article
Retrouvey JM, Taqi D, Tamimi F, Dagdeviren D, Glorieux FH, Lee B, Hazboun R, Krakow D, Sutton VR; Members of the BBD Consortium
Eur J Med Genet 2019 Dec;62(12):103606. Epub 2018 Dec 26 doi: 10.1016/j.ejmg.2018.12.011. PMID: 30593885Free PMC Article
Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Lindahl K, Åström E, Rubin CJ, Grigelioniene G, Malmgren B, Ljunggren Ö, Kindmark A
Eur J Hum Genet 2015 Aug;23(8):1042-50. Epub 2015 May 6 doi: 10.1038/ejhg.2015.81. PMID: 25944380Free PMC Article

Recent systematic reviews

Ventura L, Verdonk SJE, Zhytnik L, Ridwan-Pramana A, Gilijamse M, Schreuder WH, van Gelderen-Ziesemer KA, Schoenmaker T, Micha D, Eekhoff EMW
Calcif Tissue Int 2024 Nov;115(5):461-479. Epub 2024 Sep 18 doi: 10.1007/s00223-024-01293-2. PMID: 39294450Free PMC Article
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
Ashournia H, Johansen FT, Folkestad L, Diederichsen AC, Brixen K
Int J Cardiol 2015 Oct 1;196:149-57. Epub 2015 Jun 14 doi: 10.1016/j.ijcard.2015.06.001. PMID: 26100571
Sinikumpu JJ, Ojaniemi M, Lehenkari P, Serlo W
Injury 2015 Aug;46(8):1440-6. Epub 2015 Apr 22 doi: 10.1016/j.injury.2015.04.021. PMID: 25943292
Cui Y, Zhao H, Liu Z, Liu C, Luan J, Zhou X, Han J
Orphanet J Rare Dis 2012 Aug 22;7:55. doi: 10.1186/1750-1172-7-55. PMID: 22913777Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

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

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...