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IMPERFECTA
Earliest known case of osteogenesis
imperfecta in a partially mummified infant’s
skeleton from ancient Egypt now housed in
the British Museum in London.
In 1835, Lobstein coined the term
osteogenesis imperfecta
Other names for OI: Lobstein disease, brittle-
bone disease, blue-sclera syndrome, and
fragile-bone disease
Manifest itself with 1 or more of
the following findings:
Blue sclerae
Triangular facies
Macrocephaly
Hearing loss
Defective dentition
Barrel chest
Scoliosis
Limb deformities
Fractures
Joint laxity
Growth retardation
Constipation and sweating
Pathologic changes seen in all tissues in which
type 1 collagen is an important constituent (eg,
bone, ligament, dentin, and sclera)
Basic defect : qualitative or quantitative reduction
in type 1 collagen
Mutations in genes encoding type 1 collagen affect
the coding of 1 of the 2 genes
Mutations are either genetically inherited or new
Inherited mutations : recurrence risk in
subsequent pregnancies of 50% if a parent is
affected
New mutations unpredictable recurrence risk
Quantitative defects of
type 1 collagen : mutations
on COL1A gene, production
of premature stop codon or
a microsense frame
shift, which leads to mutant
messenger RNA (mRNA) in
the nucleus
Cytoplasm contains normal
alpha1 mRNA; reduced
amounts of structurally
normal collagen produced
Mild form of disease
Qualitative defects of
type 1 collagen:
autosomal dominant
mutations on either
the COL1A or
the COL1B gene,
production of mixture of
normal and mutant
collagen chainstype 1
collagen thus formed is
functionally impaired
because of mutant
chain
In bone :both endochondral
and intramembranous
ossification affected
Epiphysis and physis :broad
and irregular, with
disorganization of proliferative
and hypertrophic zones ,loss
of typical columnar
arrangement, thinning of zone
of calcified cartilage,
deficiency of primary
spongiosa of the metaphysis
and delay of the secondary
centers of ossification in the
epiphysis.
Scoliosis and kyphosis
Vertebral bodies
:wedged, translucent,
and shallow
Thinning of the skull
and multiple
ossification centers
(wormian bones) are
present, particularly in
the occiput
Epidemiology
Clinical presentation
depends on phenotype
Sillence classificatiom : 4
types on basis of
clinical and radiologic
features
Dentinogenesis
imperfecta denoted as
subtype B, whereas OI
without dentinogenesis
imperfecta is denoted
as subtype A
Many cases of OI do not fit into the
aforementioned categories; osteoporosis-
pseudoglioma, Bruck syndrome, and Cole-
Carpenter syndrome.
Osteoporosis-pseudoglioma syndrome :
caused by mutations in gene encoding
for low-density-lipoprotein receptor-
related protein 5 (LRP5), with clinical
features including blindness and bone
fragility
Bruck syndrome: autosomal recessive
condition caused by mutations in bone-
specific collagen type 1 telopeptide lysyl
hydroxylase enzyme, with clinical features that
include congenital joint contractures and
bone fragility
Cole-Carpenter syndrome : severe progressive
form of OI, with associated multisutural
craniosynostosis and growth failure
Complications
Repeated respiratory
infections
Basilar impression caused
by a large head, which
causes brainstem
compression
Cerebral
hemorrhage caused
by birth trauma
High risk for
complications of
anesthesia
Diagnostic Considerations
Differential
diagnoses
categorized into 3
stages of life:
Prenatal/neonata
l
Preschool/childh
ood
Adolescence/adultho
od
Conditions that should be
considered in
prenatal/neonatal stage
include:
Jeune dystrophy
Camptomelic dysplasia
Chondrodysplasia
punctata
Chondroectodermal
dysplasia (Ellis–van Creveld
syndrome)
Nonaccidental injury
Hypophosphatasia
Preschool/childhood
stage include:
Pyknodysostosis
Hajdu-Cheney
syndrome
Osteochondro
matosis
Nonaccidenta
l injury
Differentiate between OI and child
abuse
Keys to distinguishing OI from
child :
Metaphyseal corner fractures,
which are common in child abuse,
rare in OI
In children with OI, fractures may
continue to occur while they are
in protective custody
Child abuse has nonskeletal
manifestations (eg, retinal
hemorrhage, visceral intramural
hematomas, intracranial bleeds
of various ages, pancreatitis, and
splenic trauma)
Differential Diagnoses
Achondroplasia
Menkes Kinky Hair Disease
Glucocorticoid Therapy
Cushing Syndrome
Homocysteinemia
McCune-Albright Syndrome
Osteopetrosis
Osteoporosis
Pediatric Acute Lymphoblastic
Leukemia
Rickets
Scurvy
Thanatophoric Dysplasia
Wilson Disease
Laboratory Studies