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Osteogenesis imperfecta type 16(OI16)

MedGen UID:
864047
Concept ID:
C4015610
Disease or Syndrome
Synonyms: OI, TYPE XVI; Osteogenesis imperfecta, type xvi
 
Gene (location): CREB3L1 (11p11.2)
 
Monarch Initiative: MONDO:0014544
OMIM®: 616229

Definition

Osteogenesis imperfecta type XVI (OI16) is characterized by prenatal onset of multiple fractures of ribs and long bones, blue sclerae, decreased ossification of the skull, and severe demineralization. Heterozygous family members may exhibit recurrent fractures with minimal trauma, osteopenia, and blue sclerae (Keller et al., 2018; Lindahl et al., 2018). [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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.

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

Clinical features

From HPO
Mesomelia
MedGen UID:
107808
Concept ID:
C0549306
Congenital Abnormality
Shortening of the middle parts of the limbs (forearm and lower leg) in relation to the upper and terminal segments.
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Angulated humerus
MedGen UID:
871081
Concept ID:
C4025546
Finding
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
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).
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Prolonged bleeding time
MedGen UID:
56231
Concept ID:
C0151529
Finding
Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
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.
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.
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).
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
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.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Bowing of the long bones
MedGen UID:
340849
Concept ID:
C1855340
Congenital Abnormality
A bending or abnormal curvature of a long bone.
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.
Tooth agenesis
MedGen UID:
869773
Concept ID:
C4024202
Finding
The absence of one or more teeth from the normal series by a failure to develop
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

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
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

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
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
LoMauro A, Landoni CV, Fraschini P, Molteni F, Aliverti A, Bertoli S, De Amicis R
Orphanet J Rare Dis 2021 Oct 18;16(1):435. doi: 10.1186/s13023-021-02058-y. PMID: 34663416Free PMC Article
Dimitrakakis G, Challoumas D, von Oppell UO
Interact Cardiovasc Thorac Surg 2014 Sep;19(3):499-504. Epub 2014 May 29 doi: 10.1093/icvts/ivu152. PMID: 24876219
Bishop N
Endocr Dev 2009;16:157-69. Epub 2009 Jun 3 doi: 10.1159/000223694. PMID: 19494666

Diagnosis

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
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
Bardai G, Moffatt P, Glorieux FH, Rauch F
Osteoporos Int 2016 Dec;27(12):3607-3613. Epub 2016 Aug 11 doi: 10.1007/s00198-016-3709-1. PMID: 27509835
Dimitrakakis G, Challoumas D, von Oppell UO
Interact Cardiovasc Thorac Surg 2014 Sep;19(3):499-504. Epub 2014 May 29 doi: 10.1093/icvts/ivu152. PMID: 24876219
Bishop N
Endocr Dev 2009;16:157-69. Epub 2009 Jun 3 doi: 10.1159/000223694. PMID: 19494666

Therapy

Sagar RL, Åström E, Chitty LS, Crowe B, David AL, DeVile C, Forsmark A, Franzen V, Hermeren G, Hill M, Johansson M, Lindemans C, Lindgren P, Nijhuis W, Oepkes D, Rehberg M, Sahlin NE, Sakkers R, Semler O, Sundin M, Walther-Jallow L, Verweij EJTJ, Westgren M, Götherström C
BMJ Open 2024 Jun 4;14(6):e079767. doi: 10.1136/bmjopen-2023-079767. PMID: 38834319Free PMC Article
Erbaş İM, İlgün Gürel D, Manav Kabayeğit Z, Koç A, Ünüvar T, Abacı A, Böber E, Anık A
Connect Tissue Res 2022 Jul;63(4):349-358. Epub 2021 Jun 9 doi: 10.1080/03008207.2021.1932853. PMID: 34107839
Vuorimies I, Mäyränpää MK, Valta H, Kröger H, Toiviainen-Salo S, Mäkitie O
J Clin Endocrinol Metab 2017 Apr 1;102(4):1333-1339. doi: 10.1210/jc.2016-3745. PMID: 28323993
Dimitrakakis G, Challoumas D, von Oppell UO
Interact Cardiovasc Thorac Surg 2014 Sep;19(3):499-504. Epub 2014 May 29 doi: 10.1093/icvts/ivu152. PMID: 24876219
Bishop N
Endocr Dev 2009;16:157-69. Epub 2009 Jun 3 doi: 10.1159/000223694. PMID: 19494666

Prognosis

Evin F, Atik T, Onay H, Goksen D, Darcan S, Cogulu O, Ozen S
J Pediatr Endocrinol Metab 2024 Aug 27;37(8):693-700. Epub 2024 Jul 3 doi: 10.1515/jpem-2024-0058. PMID: 38953412
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
LoMauro A, Landoni CV, Fraschini P, Molteni F, Aliverti A, Bertoli S, De Amicis R
Orphanet J Rare Dis 2021 Oct 18;16(1):435. doi: 10.1186/s13023-021-02058-y. PMID: 34663416Free PMC Article
Yimgang DP, Shapiro JR
J Matern Fetal Neonatal Med 2016;29(14):2358-62. Epub 2015 Sep 15 doi: 10.3109/14767058.2015.1085965. PMID: 26372357
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

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
LoMauro A, Landoni CV, Fraschini P, Molteni F, Aliverti A, Bertoli S, De Amicis R
Orphanet J Rare Dis 2021 Oct 18;16(1):435. doi: 10.1186/s13023-021-02058-y. PMID: 34663416Free PMC Article
Martins G, Siedlikowski M, Coelho AKS, Rauch F, Tsimicalis A
J Pediatr (Rio J) 2020 Jul-Aug;96(4):472-478. Epub 2019 Feb 22 doi: 10.1016/j.jped.2018.12.008. PMID: 30802423Free PMC Article
Bardai G, Moffatt P, Glorieux FH, Rauch F
Osteoporos Int 2016 Dec;27(12):3607-3613. Epub 2016 Aug 11 doi: 10.1007/s00198-016-3709-1. PMID: 27509835
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

Prado HV, Soares ECB, Carneiro NCR, Vilar ICO, Abreu LG, Borges-Oliveira AC
J Appl Oral Sci 2023;31:e20230040. Epub 2023 Sep 4 doi: 10.1590/1678-7757-2023-0040. PMID: 37672427Free PMC Article
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

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