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In Depth Tutorials and Information
III, type IV OI is due to a qualitative defect in type I col-
lagen synthesis. The mode of inheritance is autosomal
dominant.
More recently, other forms of OI have been iden-
tified. OI type V constitutes about 4 to 5% of the OI
patients seen in hospitals.
5
The phenotype of this group
of patients is characterized by moderate to severe bone
fragility, white sclera and absent DI. Dense metaphyseal
bands appear adjacent to the growth plates on radio-
graphs. The most distinctive feature in these patients is
the presence of hypertrophic callus formation, and early
calcification of the interosseous membrane of the fore-
arm that limits pronation and supination and can lead to
dislocation of the radial head.
6-9
Unlike the forms of OI
described above, DNA and protein screening have failed
to identify an underlying genetic defect of type I colla-
gen. The inheritance is autosomal dominant.
Patients who have type VI OI present with moderate
to severe skeletal deformity. These individuals do not
have DI or blue sclera. Biopsy specimens under light
microscopy show a fish scale-like appearance of the bone
lamellae and an excessive presence of osteoid. As in type
V OI, there is no identifiable defect of the type I collagen
genes. Unlike the majority of OI patients, the mode of
inheritance is autosomal recessive.
10
Type VII OI is characterized by moderate to severe
deformity and fragility. Typical features of this form of
OI include rhizomelia and coxa vara, which can be pres-
ent in infancy. Type VII OI was first observed in a com-
munity of Native Americans in northern Quebec.
11
Like
type VI OI, this form of OI also has an autosomal reces-
sive form of inheritance.
12
In addition to types VI and
VII, newer autosomal dominant forms of the disorder
have also been described.
13
These autosomal recessive
forms are caused by a deficiency of proteins that are
involved in post-translational modification or folding of
the type I procollagen molecule.
Shapiro
14
introduced a clinical classification scheme
that he proposed be used to predict the survival and
walking ability of patients with OI. In this system,
patients are classified according to the time of the initial
fracture and the radiographic appearance of their long
bones and ribs. Patients who have intrauterine or birth
fractures are classified as OI congenita (OIC). These are
further subdivided into subgroups A and B. In subgroup
A, radiographs show short, broad, crumpled femurs and
ribs whereas, in subgroup B, radiographs show bones
with normal contours. In contrast to OIC, individuals
who sustain their first fracture after birth are classified
as OI tarda (OIT). These patients are further subdivided
into subgroup A, who sustain their first fracture before
walking has begun, and subgroup B, who suffer their
first fracture after walking has begun.
The author found that survival was poor in patients
classified as OIC-A. In his report, 14 of 16 OIC-A patients
died before 2 years of age. By comparison, survival
of OIC-B patients was much better; however, many
required a wheelchair for mobility. The prognosis for
ambulation was better in OIT patients. That is, two-
thirds of OIT-A patients and all OIT-B patients were
ambulatory. While this scheme is not commonly used,
it does serve to point out that the severity of this clini-
cally diverse disorder markedly influences longevity and
function in children who have OI.
EV
ALUATION AND DIAGNO
SIS
Because of the wide range of severity, OI may pres-
ent in patients at any age. In the more severe forms,
the diagnosis may be evident before birth on a prenatal
ultrasound, at the time of birth or during early infancy.
The milder forms of the disorder may not become appar-
ent until childhood or the early teen years. As well, some
adult patients with OI elude diagnosis until one of their
affected children seeks treatment of a fracture.
5
When the patient is first seen, the clinician should
attempt to identify the clinical features of OI. Classifying
the patient as to the type of OI may be helpful to pro-
vide information about prognosis and help guide man-
agement, although the wide phenotypic diversity, even
within the same type, should be kept in mind.
15,16
The diagnosis of OI is largely established by clinical
examination. It is based upon the family history, history
of fractures and characteristic findings such as scleral
hue and appearance of the teeth. Plain radiographs may
be useful to aid in defining the phenotype by showing
fractures of varying ages, deformity of the long bones,
spine and osteopenia. Radiographs of the skull may be
of use as well. In a recent study, Wormian bones of the
skull were observed in 35% of patients with OI type I, in
96% of patients with OI type III and in 78% of patients
with OI type IV.
17
Biochemical tests of bone turnover are
generally not helpful.
18
While some authors have sug-
gested that evaluation of bone density may be helpful in
detecting low bone mineral density that may be missed
on plain radiographs of children with milder forms of
OI,
19,20
others feel that testing is of little diagnostic value,
and can be difficult to perform and interpret when there
is deformity and short stature.
18
Recently, Huang and
colleagues
21
found assessment of bone mineral density
using dual X-ray absorptiometry to be useful in deter-
mining severity of disease, the risk for future fractures
and the long-term functional outcome in children with
OI. Bone density testing is most commonly used to mon-
itor the response to treatment.
Genetic testing for OI can be done either by analysis of
the structure and quantity of type I collagen synthesized
by cultured fibroblasts from a skin biopsy
22,23
or by direct
assessment of DNA extracted from blood. Both types
