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Osteogenesis imperfecta type 12(OI12)

MedGen UID:
462783
Concept ID:
C3151433
Disease or Syndrome
Synonyms: OI, TYPE XII; OI12; Osteogenesis imperfecta, type XII; SP7-Related Osteogenesis Imperfecta
 
Gene (location): SP7 (12q13.13)
 
Monarch Initiative: MONDO:0013460
OMIM®: 613849

Definition

Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XII is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, progressive hearing loss, no dentinogenesis imperfecta, and white sclerae (summary by Lapunzina et al., 2010). [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
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
Abnormality of cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Congenital Abnormality
Any structural anomaly of the heart and great vessels.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Progressive hearing impairment
MedGen UID:
331224
Concept ID:
C1842138
Finding
A progressive form of hearing impairment.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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).
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Bowing of the arm
MedGen UID:
488899
Concept ID:
C0426863
Finding
A bending or abnormal curvature affecting a long bone of the arm.
Genu varum
MedGen UID:
154257
Concept ID:
C0544755
Finding
A positional abnormality marked by outward bowing of the legs in which the knees stay wide apart when a person stands with the feet and ankles together.
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Brachyturricephaly
MedGen UID:
387833
Concept ID:
C1857484
Finding
Abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
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.
Generalized osteoporosis
MedGen UID:
1639139
Concept ID:
C4551680
Disease or Syndrome
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Prominent supraorbital ridges
MedGen UID:
333982
Concept ID:
C1842060
Finding
Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Abnormal sclera morphology
MedGen UID:
871347
Concept ID:
C4025840
Anatomical Abnormality
An abnormality of the sclera.

Professional guidelines

PubMed

Trejo P, Rauch F
Osteoporos Int 2016 Dec;27(12):3427-3437. Epub 2016 Aug 5 doi: 10.1007/s00198-016-3723-3. PMID: 27492436
Biggin A, Munns CF
Curr Osteoporos Rep 2014 Sep;12(3):279-88. doi: 10.1007/s11914-014-0225-0. PMID: 24964776
Pope FM, Daw SC, Narcisi P, Richards AR, Nicholls AC
J Inherit Metab Dis 1989;12 Suppl 1:135-73. doi: 10.1007/BF01799292. PMID: 2572730

Recent clinical studies

Etiology

Chen P, Zhou Y, Tan Z, Lin Y, Lin DL, Wu J, Li Z, Shek HT, Wu J, Hu Y, Zhu F, Chan D, Cheung KM, To MK
Orphanet J Rare Dis 2023 Sep 20;18(1):295. doi: 10.1186/s13023-023-02906-z. PMID: 37730650Free PMC Article
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Ballenger KL, Tugarinov N, Talvacchio SK, Knue MM, Dang Do AN, Ahlman MA, Reynolds JC, Yanovski JA, Marini JC
J Clin Endocrinol Metab 2022 Jan 1;107(1):67-76. doi: 10.1210/clinem/dgab679. PMID: 34519823Free PMC Article
Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2016 Oct 19;10(10):CD005088. doi: 10.1002/14651858.CD005088.pub4. PMID: 27760454Free PMC Article

Diagnosis

Menezes AH, Traynelis VC
Childs Nerv Syst 2022 Feb;38(2):361-377. Epub 2021 Nov 22 doi: 10.1007/s00381-021-05409-z. PMID: 34806157
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Trejo P, Rauch F
Osteoporos Int 2016 Dec;27(12):3427-3437. Epub 2016 Aug 5 doi: 10.1007/s00198-016-3723-3. PMID: 27492436
Biggin A, Munns CF
Curr Osteoporos Rep 2014 Sep;12(3):279-88. doi: 10.1007/s11914-014-0225-0. PMID: 24964776

Therapy

Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2016 Oct 19;10(10):CD005088. doi: 10.1002/14651858.CD005088.pub4. PMID: 27760454Free PMC Article
Trejo P, Rauch F
Osteoporos Int 2016 Dec;27(12):3427-3437. Epub 2016 Aug 5 doi: 10.1007/s00198-016-3723-3. PMID: 27492436
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2014 Jul 23;(7):CD005088. doi: 10.1002/14651858.CD005088.pub3. PMID: 25054949
Biggin A, Munns CF
Curr Osteoporos Rep 2014 Sep;12(3):279-88. doi: 10.1007/s11914-014-0225-0. PMID: 24964776

Prognosis

Alcorta-Sevillano N, Macías I, Infante A, Rodríguez CI
Cells 2020 Dec 7;9(12) doi: 10.3390/cells9122630. PMID: 33297501Free PMC Article
Bronheim R, Khan S, Carter E, Sandhaus RA, Raggio C
Spine (Phila Pa 1976) 2019 Aug 1;44(15):1057-1063. doi: 10.1097/BRS.0000000000003012. PMID: 31335789
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Smith R, Athanasou NA, Ostlere SJ, Vipond SE
QJM 1995 Dec;88(12):865-78. PMID: 8593546
Thompson EM, Young ID, Hall CM, Pembrey ME
J Med Genet 1987 Jul;24(7):390-405. doi: 10.1136/jmg.24.7.390. PMID: 3612715Free PMC Article

Clinical prediction guides

Menezes AH, Traynelis VC
Childs Nerv Syst 2022 Feb;38(2):361-377. Epub 2021 Nov 22 doi: 10.1007/s00381-021-05409-z. PMID: 34806157
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
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
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2016 Oct 19;10(10):CD005088. doi: 10.1002/14651858.CD005088.pub4. PMID: 27760454Free PMC Article

Recent systematic reviews

Ying ZM, Hu B, Yan SG
Orthop Surg 2020 Aug;12(4):1293-1303. Epub 2020 Jun 26 doi: 10.1111/os.12611. PMID: 32589343Free PMC Article
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2016 Oct 19;10(10):CD005088. doi: 10.1002/14651858.CD005088.pub4. PMID: 27760454Free PMC Article
Dwan K, Phillipi CA, Steiner RD, Basel D
Cochrane Database Syst Rev 2014 Jul 23;(7):CD005088. doi: 10.1002/14651858.CD005088.pub3. PMID: 25054949
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
Phillipi CA, Remmington T, Steiner RD
Cochrane Database Syst Rev 2008 Oct 8;(4):CD005088. doi: 10.1002/14651858.CD005088.pub2. PMID: 18843680

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