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Osteogenesis imperfecta, perinatal lethal(OI2)

MedGen UID:
75673
Concept ID:
C0268358
Congenital Abnormality; Disease or Syndrome
Synonyms: OI, TYPE II; OI2; Osteogenesis imperfecta congenita; Osteogenesis imperfecta congenita perinatal lethal form; Osteogenesis imperfecta type 2; Osteogenesis imperfecta, dominant perinatal lethal; OSTEOGENESIS IMPERFECTA, TYPE II; Vrolik type of osteogenesis imperfecta
SNOMED CT: Osteogenesis imperfecta, dominant perinatal lethal (7134007); Osteogenesis imperfecta type II, dominant form (7134007); Neonatal lethal osteogenesis imperfecta congenita (7134007); Osteogenesis imperfecta, perinatal lethal (205496008); Osteogenesis imperfecta type II (205496008); Osteogenesis imperfecta, type II (205496008); Osteogenesis imperfecta type IIA (254110009); Osteogenesis imperfecta congenita neonatal lethal form (254110009); Osteogenesis imperfecta, neonatal lethal (254110009); Lethal osteogenesis imperfecta (205496008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): COL1A1 (17q21.33); COL1A2 (7q21.3)
 
Monarch Initiative: MONDO:0008147
OMIM®: 166210
Orphanet: ORPHA216804

Disease characteristics

Excerpted from the GeneReview: COL1A1/2 Osteogenesis Imperfecta
COL1A1/2 osteogenesis imperfecta (COL1A1/2-OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent, wear down, and break easily. COL1A1/2-OI has been classified into four types based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four more common OI types are now referred to as follows: Classic non-deforming OI with blue sclerae (previously OI type I). Perinatally lethal OI (previously OI type II). Progressively deforming OI (previously OI type III). Common variable OI with normal sclerae (previously OI type IV). [from GeneReviews]
Authors:
Robert D Steiner  |  Donald Basel   view full author information

Additional description

From OMIM
Osteogenesis imperfecta type II (OI2) is a connective tissue disorder characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency (Sillence et al., 1979; Barnes et al., 2006). Also see osteogenesis imperfecta type VII (OI7; 610682), an autosomal recessive form of lethal OI caused by mutation in the CRTAP gene (605497).  http://www.omim.org/entry/166210

Clinical features

From HPO
Limb undergrowth
MedGen UID:
116086
Concept ID:
C0239399
Finding
Limb shortening because of underdevelopment of one or more bones of the extremities.
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Pulmonary valve insufficiency
MedGen UID:
11031
Concept ID:
C0034088
Pathologic Function
The retrograde (backwards) flow of blood through the pulmonary valve into the right ventricle during diastole.
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.
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.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
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.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
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.
Bell-shaped thorax
MedGen UID:
351320
Concept ID:
C1865186
Finding
The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.
Crumpled long bones
MedGen UID:
370928
Concept ID:
C1970497
Finding
An crumpled radiographic appearance of the long bones, as if the long bone had been crushed together producing irregularities. This feature is the result of multiple fractures and repeated rounds of ineffective healing, as can be seen for instance in severe forms of osteogenesis imperfecta.
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.
Abnormal pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Absent ossification of calvaria
MedGen UID:
867269
Concept ID:
C4021629
Anatomical Abnormality
Acalvaria is an extremely rare congenital malformation characterized by an absence of flat bones of skull, dura mater, and associated muscles in the presence of normal cranial contents and facial bones.
Broad long bones
MedGen UID:
867270
Concept ID:
C4021630
Finding
Increased cross-section (diameter) of the long bones. Note that widening may primarily affect specific regions of long bones (e.g., diaphysis or metaphysis), but this should be coded separately.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Non-immune hydrops fetalis
MedGen UID:
105327
Concept ID:
C0455988
Disease or Syndrome
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Nishimura G, Handa A, Miyazaki O, Tsujioka Y, Murotsuki J, Sawai H, Yamada T, Kozuma Y, Takahashi Y, Ozawa K, Pooh R, Sase M
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Offiah AC, Vockley J, Munns CF, Murotsuki J
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Harrington J, Sochett E, Howard A
Pediatr Clin North Am 2014 Dec;61(6):1243-57. Epub 2014 Sep 22 doi: 10.1016/j.pcl.2014.08.010. PMID: 25439022

Recent clinical studies

Etiology

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Endocr Dev 2015;28:56-71. Epub 2015 Jun 12 doi: 10.1159/000380992. PMID: 26138835
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Thompson EM
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Diagnosis

Nishimura G, Handa A, Miyazaki O, Tsujioka Y, Murotsuki J, Sawai H, Yamada T, Kozuma Y, Takahashi Y, Ozawa K, Pooh R, Sase M
Br J Radiol 2023 Jul;96(1147):20221025. doi: 10.1259/bjr.20221025. PMID: 37351952Free PMC Article
Deguchi M, Tsuji S, Katsura D, Kasahara K, Kimura F, Murakami T
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Offiah AC, Vockley J, Munns CF, Murotsuki J
Pediatr Radiol 2019 Jan;49(1):3-22. Epub 2018 Oct 3 doi: 10.1007/s00247-018-4239-0. PMID: 30284005Free PMC Article
Calder AD
Endocr Dev 2015;28:56-71. Epub 2015 Jun 12 doi: 10.1159/000380992. PMID: 26138835
Kocher MS, Shapiro F
J Am Acad Orthop Surg 1998 Jul-Aug;6(4):225-36. doi: 10.5435/00124635-199807000-00004. PMID: 9682085

Therapy

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Hoyer-Kuhn H, Stark C, Franklin J, Schoenau E, Semler O
Pediatr Endocrinol Rev 2017 Nov;15(Suppl 1):123-129. doi: 10.17458/per.vol15.2017.hsf.correlationbonemineraldensity. PMID: 29292876
Harrington J, Sochett E, Howard A
Pediatr Clin North Am 2014 Dec;61(6):1243-57. Epub 2014 Sep 22 doi: 10.1016/j.pcl.2014.08.010. PMID: 25439022
Vogel BE, Minor RR, Freund M, Prockop DJ
J Biol Chem 1987 Oct 25;262(30):14737-44. PMID: 3667599

Prognosis

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Bodian DL, Chan TF, Poon A, Schwarze U, Yang K, Byers PH, Kwok PY, Klein TE
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Thompson EM, Young ID, Hall CM, Pembrey ME
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Clinical prediction guides

Sałacińska K, Pinkier I, Rutkowska L, Chlebna-Sokół D, Jakubowska-Pietkiewicz E, Michałus I, Kępczyński Ł, Salachna D, Wieczorek-Cichecka N, Piotrowicz M, Chilarska T, Jamsheer A, Matusik P, Wilk M, Petriczko E, Giżewska M, Stecewicz I, Walczak M, Rybak-Krzyszkowska M, Lewiński A, Gach A
Front Endocrinol (Lausanne) 2023;14:1149982. Epub 2023 Sep 22 doi: 10.3389/fendo.2023.1149982. PMID: 37810882Free PMC Article
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Bodian DL, Chan TF, Poon A, Schwarze U, Yang K, Byers PH, Kwok PY, Klein TE
Hum Mol Genet 2009 Feb 1;18(3):463-71. Epub 2008 Nov 7 doi: 10.1093/hmg/ddn374. PMID: 18996919Free PMC Article
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
Bateman JF, Chan D, Mascara T, Rogers JG, Cole WG
Biochem J 1986 Dec 15;240(3):699-708. doi: 10.1042/bj2400699. PMID: 3827862Free PMC Article

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