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Osteogenesis imperfecta type 14(OI14)

MedGen UID:
767342
Concept ID:
C3554428
Disease or Syndrome
Synonyms: OI, TYPE XIV; Osteogenesis imperfecta, type xiv
 
Gene (location): TMEM38B (9q31.2)
 
Monarch Initiative: MONDO:0014029
OMIM®: 615066

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 cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Shaheen et al. (2012) described osteogenesis imperfecta type XIV (OI14), an autosomal recessive form of the disorder characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years. [from OMIM]

Additional description

From MedlinePlus Genetics
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.

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
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).
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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.
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).
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.
Increased susceptibility to fractures
MedGen UID:
234655
Concept ID:
C1390474
Finding
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.
Slender long bone
MedGen UID:
331446
Concept ID:
C1833144
Finding
Reduced diameter of a long bone.
Thin bony cortex
MedGen UID:
318844
Concept ID:
C1833325
Finding
Abnormal thinning of the cortical region of bones.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
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.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Abnormal circulating calcium concentration
MedGen UID:
868059
Concept ID:
C4022450
Finding
Any deviation from the normal concentration of calcium in the blood circulation.
Increased circulating beta-C-terminal telopeptide concentration
MedGen UID:
1614490
Concept ID:
C4531129
Finding
A abnormal elevation above the normal concentration of beta-C-terminal telopeptide of type I collagen in the blood circulation.
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
Mohd Nawawi N, Selveindran NM, Rasat R, Chow YP, Abdul Latiff Z, Syed Zakaria SZ, Jamal R, Abdul Murad NA, Abd Aziz BB
Clin Chim Acta 2018 Sep;484:141-147. Epub 2018 May 25 doi: 10.1016/j.cca.2018.05.048. PMID: 29807018
Thomas IH, DiMeglio LA
Curr Osteoporos Rep 2016 Feb;14(1):1-9. doi: 10.1007/s11914-016-0299-y. PMID: 26861807

Recent clinical studies

Etiology

Correia Barão R, Santos M, Marques RE, Quintas AM, Guerra P
Graefes Arch Clin Exp Ophthalmol 2023 Sep;261(9):2585-2592. Epub 2023 Apr 19 doi: 10.1007/s00417-023-06059-4. PMID: 37074408Free PMC Article
Ross J, Bowden MR, Yu C, Diaz-Thomas A
Front Endocrinol (Lausanne) 2023;14:1137976. Epub 2023 Mar 17 doi: 10.3389/fendo.2023.1137976. PMID: 37008909Free 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
Womack J
Adv Neonatal Care 2014 Oct;14(5):309-15; quiz 316-7. doi: 10.1097/ANC.0000000000000094. PMID: 24950034
Smith R, Athanasou NA, Ostlere SJ, Vipond SE
QJM 1995 Dec;88(12):865-78. PMID: 8593546

Diagnosis

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: 39294450
Paduano F, Fischetto R, Moretti B, De Vito D, Tatullo M
Front Endocrinol (Lausanne) 2023;14:1254695. Epub 2023 Oct 20 doi: 10.3389/fendo.2023.1254695. PMID: 37929041Free PMC Article
Correia Barão R, Santos M, Marques RE, Quintas AM, Guerra P
Graefes Arch Clin Exp Ophthalmol 2023 Sep;261(9):2585-2592. Epub 2023 Apr 19 doi: 10.1007/s00417-023-06059-4. PMID: 37074408Free PMC Article
Ross J, Bowden MR, Yu C, Diaz-Thomas A
Front Endocrinol (Lausanne) 2023;14:1137976. Epub 2023 Mar 17 doi: 10.3389/fendo.2023.1137976. PMID: 37008909Free PMC Article
Womack J
Adv Neonatal Care 2014 Oct;14(5):309-15; quiz 316-7. doi: 10.1097/ANC.0000000000000094. PMID: 24950034

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
Eaton V, Braaten M, Schissel M, Wallace M
J Pediatr Orthop 2024 Jan 1;44(1):e73-e78. Epub 2023 Sep 26 doi: 10.1097/BPO.0000000000002524. PMID: 37750572Free PMC Article
Blank M, McGregor NE, Rowley L, Kung LHW, Crimeen-Irwin B, Poulton IJ, Walker EC, Gooi JH, Lamandé SR, Sims NA, Bateman JF
J Cell Mol Med 2022 Jul;26(14):4021-4031. Epub 2022 Jun 14 doi: 10.1111/jcmm.17437. PMID: 35701367Free PMC Article
Glorieux FH, Devogelaer JP, Durigova M, Goemaere S, Hemsley S, Jakob F, Junker U, Ruckle J, Seefried L, Winkle PJ
J Bone Miner Res 2017 Jul;32(7):1496-1504. Epub 2017 Apr 19 doi: 10.1002/jbmr.3143. PMID: 28370407
Thomas IH, DiMeglio LA
Curr Osteoporos Rep 2016 Feb;14(1):1-9. doi: 10.1007/s11914-016-0299-y. PMID: 26861807

Prognosis

Ross J, Bowden MR, Yu C, Diaz-Thomas A
Front Endocrinol (Lausanne) 2023;14:1137976. Epub 2023 Mar 17 doi: 10.3389/fendo.2023.1137976. PMID: 37008909Free 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
Harsevoort AGJ, Gooijer K, van Dijk FS, van der Grijn DAFM, Franken AAM, Dommisse AMV, Janus GJM
BMC Musculoskelet Disord 2020 Jan 3;21(1):6. doi: 10.1186/s12891-019-3000-7. PMID: 31900144Free 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
Smith R, Athanasou NA, Ostlere SJ, Vipond SE
QJM 1995 Dec;88(12):865-78. PMID: 8593546

Clinical prediction guides

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
Harsevoort AGJ, Gooijer K, van Dijk FS, van der Grijn DAFM, Franken AAM, Dommisse AMV, Janus GJM
BMC Musculoskelet Disord 2020 Jan 3;21(1):6. doi: 10.1186/s12891-019-3000-7. PMID: 31900144Free 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
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
Glorieux FH, Devogelaer JP, Durigova M, Goemaere S, Hemsley S, Jakob F, Junker U, Ruckle J, Seefried L, Winkle PJ
J Bone Miner Res 2017 Jul;32(7):1496-1504. Epub 2017 Apr 19 doi: 10.1002/jbmr.3143. PMID: 28370407

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: 39294450
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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