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Osteogenesis imperfecta type 7(OI7)

MedGen UID:
343981
Concept ID:
C1853162
Disease or Syndrome
Synonyms: CRTAP-Related Osteogenesis Imperfecta; OI type 2B; OI type 7; OI type IIB; OI type VII; OI7; Osteogenesis imperfecta type 2B; Osteogenesis Imperfecta Type VII; Osteogenesis imperfecta, perinatal lethal autosomal recessive; OSTEOGENESIS IMPERFECTA, TYPE IIB
 
Gene (location): CRTAP (3p22.3)
 
Monarch Initiative: MONDO:0012536
OMIM®: 610682

Definition

Osteogenesis imperfecta is a connective tissue disorder characterized by bone fragility and low bone mass. OI type VII is an autosomal recessive form of severe or lethal OI (summary by Barnes et al., 2006). [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
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Micromelia
MedGen UID:
10031
Concept ID:
C0025995
Congenital Abnormality
The presence of abnormally small extremities.
Protrusio acetabuli
MedGen UID:
98369
Concept ID:
C0409495
Anatomical Abnormality
Intrapelvic bulging of the medial acetabular wall.
Femoral retroversion
MedGen UID:
375866
Concept ID:
C1846339
Congenital Abnormality
An abnormal backward rotation of the hip relative to the knee such that the hips are externally rotated with the foot pointed outward instead of straight ahead (out-toeing).
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
Absent pulmonary artery
MedGen UID:
120560
Concept ID:
C0265905
Congenital Abnormality
A congenital defect with aplasia (absence) of one of the right or left pulmonary artery.
Hypoplastic pulmonary veins
MedGen UID:
373427
Concept ID:
C1970501
Finding
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).
Hearing abnormality
MedGen UID:
871365
Concept ID:
C4025860
Finding
An abnormality of the sensory perception of sound.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Wide cranial sutures
MedGen UID:
140825
Concept ID:
C0410935
Finding
An abnormally increased width of the cranial sutures for age-related norms (generally resulting from delayed closure).
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).
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.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
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.
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.
Bowing of the legs
MedGen UID:
1807399
Concept ID:
C5574706
Finding
A bending or abnormal curvature affecting a long bone of the leg.
Round face
MedGen UID:
116087
Concept ID:
C0239479
Finding
The facial appearance is more circular than usual as viewed from the front.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Breech presentation
MedGen UID:
654
Concept ID:
C0006157
Pathologic Function
A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first.
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.

Recent clinical studies

Etiology

Cheung MS, Glorieux FH, Rauch F
Calcif Tissue Int 2009 Mar;84(3):203-9. Epub 2009 Jan 10 doi: 10.1007/s00223-008-9211-9. PMID: 19137231

Therapy

Cheung MS, Glorieux FH, Rauch F
Calcif Tissue Int 2009 Mar;84(3):203-9. Epub 2009 Jan 10 doi: 10.1007/s00223-008-9211-9. PMID: 19137231

Prognosis

Cheung MS, Glorieux FH, Rauch F
Calcif Tissue Int 2009 Mar;84(3):203-9. Epub 2009 Jan 10 doi: 10.1007/s00223-008-9211-9. PMID: 19137231

Clinical prediction guides

Cheung MS, Glorieux FH, Rauch F
Calcif Tissue Int 2009 Mar;84(3):203-9. Epub 2009 Jan 10 doi: 10.1007/s00223-008-9211-9. PMID: 19137231