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FIGURE 15.3
(A) and (B) Anterior-posterior radiographs of the spine showing scoliosis in two patients with FKBP10 mutations demonstrat-
ing variability in the severity.
recessive OI phenotype associated with congenital and
progressive joint contractures (see below).
19
This sparked
a debate about the range of phenotypes associated with
FKBP10
mutations. Further reports on larger series of
patients identified
FKBP10
mutations in patients with
severe to moderate OI, as well as patients with OI and
contractures.
20
In response to these findings, it is sug-
gested that the phenotype be referred to as OI with and
without progressive joint contractures.
21
Numerous other authors delineated patients with
FKBP10
mutations and OI with and without joint con-
tractures.
20,22-27
Phenotypically those without contrac-
tures can present in early infancy with fractures and are
similar to a moderate to severe form of OI. Schwarze
et al.
24
described a larger cohort of individuals where a
small number of individuals presented in childhood with
pain on walking and long bone fractures. Progressive dif-
ficulty in ambulation in this form of OI appears to result
from progressive acetabular protrusio as well as scolio-
sis, though exceptions have been noted. The identified
mutations are scattered throughout the molecule and are
predicted to result in functional loss of the protein due to
frameshift, nonsense, insertion and deletion mutations.
Missense mutations have also been identified, but lead to
an unstable protein, supporting the idea that diminished
FKBP65 produces the phenotype.
Patients with
FKBP10
mutations have been treated
with bisphosphonates. There are no large data sets dem-
onstrating that bisphosphonates are highly effective in
this form of OI, but there are also no data suggesting
there is no response. Thus clinical judgment should be
used in evaluation and treatment of these patients.
BRUCK SYNDROME (BS)
Viljeon et al. in 1989
28
reported on five children in
three unrelated families who presented with an arthro-
gryposis type phenotype in the newborn period. They
had flexion contractures at the knees, ankles and feet
suggesting that there was
in utero
lack of movement
across joints. When they commenced walking, fractures
occurred and it was recognized that the patients also had
OI. The authors noted a similar case described by Bruck
in 1987,
28,29
and thus derived the origin of the eponym
associated with this disorder. The patient described by
Bruck had OI and developed contractures later in life.
The BS phenotype is an autosomal recessive form of
OI with congenital joint contractures.
30,31-35
In BS, osteo-
penia and fractures are associated with pterygia and
contractures of the large joints. Most of these children
have normal length at birth but later in life develop
