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Osteogenesis imperfecta type 15(OI15)

MedGen UID:
815174
Concept ID:
C3808844
Disease or Syndrome
Synonyms: OI, TYPE XV; Osteogenesis imperfecta, type xv; WNT1-related osteogenesis imperfecta
 
Gene (location): WNT1 (12q13.12)
 
Monarch Initiative: MONDO:0014086
OMIM®: 615220

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). Keupp et al. (2013) and Pyott et al. (2013) described osteogenesis imperfecta type XV, an autosomal recessive form of the disorder characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclera. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients. [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.

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.

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.  https://medlineplus.gov/genetics/condition/osteogenesis-imperfecta

Clinical features

From HPO
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).
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Schizencephaly
MedGen UID:
78606
Concept ID:
C0266484
Congenital Abnormality
Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness. Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see 236100).
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.
Hypoplasia of the pons
MedGen UID:
341246
Concept ID:
C1848529
Finding
Underdevelopment of the pons.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
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.
Bowing of limbs due to multiple fractures
MedGen UID:
376722
Concept ID:
C1850178
Finding
Curvature of the shafts of the long bones due to multiple fractures.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Lee CL, Liu SC, Yang CY, Chuang CK, Lin HY, Lin SP
Int J Med Sci 2021;18(5):1240-1246. Epub 2021 Jan 14 doi: 10.7150/ijms.53286. PMID: 33526985Free PMC Article
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Thompson EM
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Recent clinical studies

Etiology

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Taqi D, Moussa H, Schwinghamer T, Vieira AR, Dagdeviren D, Retrouvey JM, Rauch F, Tamimi F; Members of the BBDC
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Diagnosis

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Therapy

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Int J Med Sci 2021;18(5):1240-1246. Epub 2021 Jan 14 doi: 10.7150/ijms.53286. PMID: 33526985Free PMC Article
Peddada KV, Sullivan BT, Margalit A, Sponseller PD
J Pediatr Orthop 2018 Apr;38(4):e207-e212. doi: 10.1097/BPO.0000000000001137. PMID: 29356793
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J Bone Miner Res 2017 Sep;32(9):1884-1892. Epub 2017 Jun 26 doi: 10.1002/jbmr.3180. PMID: 28548288Free PMC Article

Prognosis

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Calcif Tissue Int 2021 Dec;109(6):633-644. Epub 2021 Jun 25 doi: 10.1007/s00223-021-00879-4. PMID: 34173012
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Int J Med Sci 2021;18(5):1240-1246. Epub 2021 Jan 14 doi: 10.7150/ijms.53286. PMID: 33526985Free 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
Rush ET, Li L, Goodwin JL, Kreikemeier RM, Craft M, Danford DA, Kutty S
Heart 2017 Mar;103(6):443-448. Epub 2016 Sep 19 doi: 10.1136/heartjnl-2016-310099. PMID: 27647171

Clinical prediction guides

Chen Y, Li G, Wei L, Weng J, Liu S, Gu M, Liu P, Zhu Y, Xiong A, Zeng H, Yu F
Front Endocrinol (Lausanne) 2023;14:1164386. Epub 2023 May 9 doi: 10.3389/fendo.2023.1164386. PMID: 37229455Free PMC Article
Venable E, Knight DRT, Thoreson EK, Baudhuin LM
Am J Med Genet C Semin Med Genet 2023 Jun;193(2):147-159. Epub 2023 Mar 9 doi: 10.1002/ajmg.c.32038. PMID: 36896471
Waissbluth S, Lira K, Aracena K, Oyarzun J, Willson M, Seiltgens C
Rev Med Chil 2020 Dec;148(12):1781-1786. doi: 10.4067/S0034-98872020001201781. PMID: 33844744
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
Van Dijk FS, Pals G, Van Rijn RR, Nikkels PG, Cobben JM
Eur J Med Genet 2010 Jan-Feb;53(1):1-5. Epub 2009 Oct 28 doi: 10.1016/j.ejmg.2009.10.007. PMID: 19878741

Recent systematic reviews

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World J Pediatr 2019 Feb;15(1):4-11. Epub 2018 Oct 20 doi: 10.1007/s12519-018-0198-7. PMID: 30343446
Beecham E, Candy B, Howard R, McCulloch R, Laddie J, Rees H, Vickerstaff V, Bluebond-Langner M, Jones L
Cochrane Database Syst Rev 2015 Mar 13;2015(3):CD010750. doi: 10.1002/14651858.CD010750.pub2. PMID: 25768935Free PMC Article

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