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Osteogenesis imperfecta type 9(OI9)

MedGen UID:
376720
Concept ID:
C1850169
Disease or Syndrome
Synonyms: OI 9; Oi type IX; OI9; Osteogenesis imperfecta sillence type II/III without abnormality of type I collagen; Osteogenesis Imperfecta Type IX; PPIB-Related Osteogenesis Imperfecta
 
Gene (location): PPIB (15q22.31)
 
Monarch Initiative: MONDO:0009805
OMIM®: 259440

Definition

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). [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
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Short lower limbs
MedGen UID:
98100
Concept ID:
C0426901
Finding
Shortening of the legs related to developmental hypoplasia of the bones of the leg.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
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).
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
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.
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.
Vertebral compression fracture
MedGen UID:
75497
Concept ID:
C0262431
Finding
Multiple rib fractures
MedGen UID:
75784
Concept ID:
C0272567
Injury or Poisoning
More than one fracture of the ribs. Callus formation around multiple rib fractures can produce a row of multiple rounded expansions (beadlike prominences) giving the appearance of beaded ribs. Note that rachitic rosary would have one bead per rib (a swelling at the costochondral junction), while beaded ribs in the context of multiple rib fractures have multiple beads (fractures) along the same rib.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Finger joint hypermobility
MedGen UID:
154359
Concept ID:
C0574974
Finding
Hip joint hypermobility
MedGen UID:
658643
Concept ID:
C0574977
Finding
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).
Diaphyseal undertubulation
MedGen UID:
331984
Concept ID:
C1835473
Finding
Tubulation refers to the size and shape of tubular bones. In children and adolescents, the modeling process regulates normal bone growth. Final shaft (tube) diameter depends on appositional bone growth and the equilibrium between periosteal and endosteal bone resorption and formation. Undertubulation refers to a broad, widened form of the shafts (diaphyses) of long bones.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
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.
Bowing of the long bones
MedGen UID:
340849
Concept ID:
C1855340
Congenital Abnormality
A bending or abnormal curvature of a long bone.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
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.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
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.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Aliyeva L, Ongen YD, Eren E, Sarisozen MB, Alemdar A, Temel SG, Sag SO
J Mol Diagn 2024 Sep;26(9):754-769. Epub 2024 Jul 20 doi: 10.1016/j.jmoldx.2024.05.014. PMID: 39025364
MacCarrick G, Aradhya S, Bailey M, Chu D, Hunt A, Izzo E, Krakow D, Mackenzie W, Poll S, Raggio C, Shediac R, White KK, McLaughlin HM, Seratti G
Am J Med Genet A 2024 Sep;194(9):e63646. Epub 2024 May 3 doi: 10.1002/ajmg.a.63646. PMID: 38702915
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

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
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Diagnosis

Lin X, Hu J, Zhou B, Zhang Q, Jiang Y, Wang O, Xia W, Xing X, Li M
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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
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Therapy

Folkestad L
Dan Med J 2018 Apr;65(4) PMID: 29619932
Peddada KV, Sullivan BT, Margalit A, Sponseller PD
J Pediatr Orthop 2018 Apr;38(4):e207-e212. doi: 10.1097/BPO.0000000000001137. PMID: 29356793
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
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Cochrane Database Syst Rev 2014 Jul 23;(7):CD005088. doi: 10.1002/14651858.CD005088.pub3. PMID: 25054949
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Prognosis

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J Endocrinol Invest 2024 Jan;47(1):67-77. Epub 2023 Jun 4 doi: 10.1007/s40618-023-02123-2. PMID: 37270749Free PMC Article
Storoni S, Treurniet S, Maugeri A, Pals G, van den Aardweg JG, van der Pas SL, Elting MW, Kloen P, Micha D, Eekhoff EMW
Front Endocrinol (Lausanne) 2022;13:869604. Epub 2022 Apr 25 doi: 10.3389/fendo.2022.869604. PMID: 35546999Free PMC Article
Alcorta-Sevillano N, Macías I, Infante A, Rodríguez CI
Cells 2020 Dec 7;9(12) doi: 10.3390/cells9122630. PMID: 33297501Free PMC Article
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Orphanet J Rare Dis 2018 Aug 22;13(1):145. doi: 10.1186/s13023-018-0887-2. PMID: 30134932Free PMC Article

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
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
Alcorta-Sevillano N, Macías I, Infante A, Rodríguez CI
Cells 2020 Dec 7;9(12) doi: 10.3390/cells9122630. PMID: 33297501Free 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

Prado HV, Soares ECB, Carneiro NCR, Vilar ICO, Abreu LG, Borges-Oliveira AC
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Dwan K, Phillipi CA, Steiner RD, Basel D
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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
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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