Congenital posteromedial bowing of the tibia and fibula, in which
both bones are medially and posteriorly bowed at either the middle or distal
third of the shaft, is an uncommon anomaly of unknown etiology and
pathogenesis1-3.
A calcaneovalgus alignment of the ipsilateral foot usually
coexists1-6.
Although the angular deformities spontaneously resolve with growth, residual
shortening (3 to 7 cm) of the tibia and fibula is typically present by
skeletal
maturity1,3,5-8.
The pathogenesis of congenital posteromedial bowing is poorly understood.
To the best of our knowledge, no description of the morphological changes in
the tibia and fibula has been reported in the literature. We report the
pathological findings in the tibia and fibula of a fetus with congenital
posteromedial bowing of the tibia and fibula, which was legally aborted during
the twenty-fourth week of gestation. We propose a possible relationship
between these findings and the etiology of this deformity.
History
A white male fetus was referred to the central postmortem facility
of our hospital to be subjected to autopsy on a routine basis. Information
accompanying the referral indicated that the fetus was the product of the
second pregnancy of nonconsanguineous, healthy parents. The mother was
thirty-six years old, and the father was fifty years of age. There was no
family history of skeletal dysplasias, musculoskeletal abnormalities, or known
exposure to teratogenic drugs. Ultrasound examination performed during the
eighteenth week of gestation had revealed normal fetal biometry (biparietal
diameter, head circumference, abdominal circumference, and femoral length) and
unilateral congenital posteromedial bowing of the right tibia and fibula as
well as calcaneovalgus alignment of the ipsilateral foot. An amniocentesis had
been performed. The volume of amniotic fluid had been reported to be normal.
Repeat ultrasound examinations in the following weeks again had confirmed the
congenital posteromedial bowing of the right tibia and fibula, and the
pregnancy had been legally ended during the twenty-fourth week of gestation.
Pathological examination of the aborted fetus included routine anteroposterior
and lateral radiographs and an autopsy.
Pathological Study
Since the preliminary results of the postmortem examination suggested a
diagnosis of isolated congenital posteromedial bowing of the tibia and fibula,
the autopsy findings and radiographs were jointly reviewed in our
musculoskeletal pathology unit by experienced bone pathologists, radiologists,
and orthopaedists. Further analysis was undertaken in order to investigate the
pathogenesis of the skeletal abnormalities. Prior to the interruption of the
pregnancy, the authors did not participate either in evaluating the ultrasound
findings or in medical counseling. The right leg was disarticulated en bloc
and was immediately fixed in 4% formaldehyde in 0.1-M phosphate buffer, pH
7.2. After decalcification in buffered EDTA, the foot was disarticulated and
the tibia was divided longitudinally. While the foot and the medial half of
the tibia were routinely processed for paraffin-embedding, transverse sections
were performed on the remaining specimens, including the lateral half of the
tibia, the fibula, and the adjacent soft tissues (skeletal muscles, fat, blood
vessels, and nerves). All of these transverse sections were routinely
processed for paraffin-embedding.
Results
A review of the radiographs (Fig.
1) and autopsy findings failed to reveal other abnormalities in
the musculoskeletal system or viscera. Thus, the pathological diagnosis was an
isolated congenital posteromedial bowing of the tibia and fibula with a
calcaneovalgus alignment of the ipsilateral foot. Gross and histological
examination of the placenta revealed it to be of normal size and weight for
gestational age. However, approximately one-half of the fetal surface was
devoid of amnion, which appeared retracted at the insertion of the umbilical
cord (Fig. 2). No features of
chorioamnionitis were seen histologically.
The lateral radiograph and gross inspection of the longitudinally divided
tibia revealed an angular deformity of approximately 50°, with the apex
located within the lower third of the bone at its medial and posterior aspect
(Fig. 3). Analysis of the
histological structure of the bone involved the use of both transverse
sections (a lateral specimen, including the lateral half of the tibia and the
fibula) and longitudinal sections (a medial specimen, including the medial
half of the tibia). The combined analysis of both types of sections
demonstrated structural changes that were essentially similar in the tibia and
fibula. Longitudinal histologic sections of the medial half of the tibia were
best suited to effectively demonstrate the changes in bone structure
associated with bowing, as shown in Figure
4. Submacroscopic views of longitudinal sections of the tibia (see
Fig. 4, A)
demonstrated an array of bone trabeculae radiating from the apex of the angle
toward the anterolateral surface. These bone trabeculae were devoid of
cartilage cores, were woven in the internal texture (as demonstrated by
polarized light microscopy), and were physically continuous with the
anterolateral cortical bone. Bone trabeculae were separated from each other by
fibrovascular tissue, which was in physical continuity with the periosteum,
and were regularly bordered by cuboidal osteoblasts, indicating bone formation
activity (see Fig. 4, B and
C). In contrast, osteoblasts were absent from the bone
surfaces at the apex of the bowing angle, where numerous multinuclear
osteoclasts engaged in bone resorption were obvious (see
Fig. 4, D and
E). Thus, active bone formation at the anterolateral
(concave) aspect of the deformed bone was coupled with active bone resorption
at the posteromedial (convex) aspect. A medullary canal was not discernible at
the apex of the posteromedial bowing. The physes were normal, and the
epiphyses were well formed and permeated by a normal-appearing system of
vascular canals.
Previous pathological studies of congenital bowing of the long bones
of the tibia and fibula have focused exclusively on anterolateral
bowing9-14
or congenital pseudarthrosis of the tibia and
fibula15. To the
best of our knowledge, the pathology of congenital posteromedial bowing has
not been reported. As a result, uncertainties remain about the etiology and
pathogenesis of this condition. In this study, we were able to investigate the
gross and histological changes associated with congenital posteromedial bowing
and, specifically, the altered pattern of prenatal ossification underlying the
deformity, which usually becomes clinically apparent only at birth.
Interestingly, in this case, restrictions to fetal movement or any evidence of
prenatal crowding or external compression relative to the deformed tibia and
fibula were not seen. However, rupture of the amnion was detected at the time
of autopsy. It is well known that intrauterine rupture of the amnion may lead
to complex fetal deformities, with limb defects and lateral abdominal or
thoracoabdominal defects (limb-body wall complex) at the more severe end of
the
spectrum16-22.
The terms amnion rupture sequence or amniotic band syndrome are commonly used
to describe the overall pattern of deformities that result from amnion
rupture, whether these are band and/or compression-related
defects16,17,20,22.
Interestingly, amnion rupture was also observed in two previously reported
cases of congenital posteromedial
bowing23,24.
Even though we could not detect either amniotic bands or constrictions around
the bowed leg at the time of the autopsy, the fetal deformity may have been
the result of mechanical teratogenesis, namely, compressive events associated
with the amnion rupture sequence. The evidence of an associated calcaneovalgus
alignment of the ipsilateral foot and the absence of abnormalities in the
patterning of the skeletal muscle of the leg support this view. However, we
were unable to demonstrate the cause of the intrauterine rupture of the
amnion; in particular, evidence of placental infection, a common and very
well-known cause of amnion rupture, was not detected. Although amniotic band
syndrome has been associated with
amniocentesis25,
the deformity described in the present study was already established in the
eighteenth week of gestation before amniocentesis was performed.
Whether resulting from transient constriction exerted by an amniotic band
or from abnormal compressive events operating along the axis of the unossified
limb bone anlage, intrauterine bowing of long bone rudiments necessarily
elicits a periosteal reaction. Consistent with this, we observed an abnormal
array of periosteal bone trabeculae radiating from the apex of the bowed tibia
and fibula. We could also demonstrate a polarized distribution of bone
formation and resorption activities at the concave and convex aspect of the
bowed tibia. This observation clearly indicates a potent modeling drift
operating prenatally in the bowed bones, with a deformity occurring at the
midshaft. As has been well established in the literature, spontaneous
correction of congenital posteromedial bowing tends to occur
postnatally1,3,5-8.
This must involve differential resorption and formation at the contralateral
sides of the deformity, as happens during normal bone
modeling26. Our
observations indicate that these events begin prenatally and are therefore
independent of mechanical loading. Possibly, tensile and compressive strains
in the periosteum, brought about by the deformity itself, suffice to elicit a
corrective modeling drift during prenatal life.
Tibial and fibular shortening, ranging from 3 to 7 cm at skeletal maturity,
is the usual, and most severe, long-term consequence of congenital
posteromedial
bowing1,3,5-8.
Proper planning of postnatal management must be considered once the diagnosis
of congenital posteromedial bowing, in the absence of accompanying disorders
or complications, is established. Although longitudinal bone growth is usually
attributed solely to the biological activity of physeal cartilage, periosteal
osteogenic cells also contribute substantially to the growth in length of
cortical
bone27,28.
In congenital posteromedial bowing, displacement of the osteogenic periosteum
results in proliferative and biosynthetic activity of osteoblasts that remain
ineffective with respect to bone elongation. As we have demonstrated,
substantial volumes of periosteal bone are deposited in an incongruous
direction, resulting in a fan-like system of periosteal bone at the site of
bowing. This ineffective osteogenesis does not contribute to longitudinal
growth but may, nonetheless, "waste" osteoblastic function and
consume osteogenic progenitor cells, detracting from the overall growth
potential of the individual bone or bones. This hypothesis would be consistent
with the notion that osteochondral progenitor cells in the periosteum decline
in frequency with age and thus represent a limited cellular pool, with limited
proliferative
potential29,30.
In conclusion, the study of the prenatal pathology associated with
congenital posteromedial bowing in the present report provides support to the
view that at least some cases of this disorder are associated with a placental
abnormality, which may result in compressive events triggered by amnion
rupture. Our study is the first, as far as we know, to document the structural
changes associated with bone bowing and characterize them as an expression of
abnormal periosteal ossification. Furthermore, our study is the first that we
know of to document the occurrence of a modeling drift, operating toward
correction of the bone deformity, during prenatal bone growth. ?
The authors did not receive grants or outside funding in support of their
research or preparation of this manuscript. They did not receive payments or
other benefits or a commitment or agreement to provide such benefits from a
commercial entity. No commercial entity paid or directed, or agreed to pay or
direct, any benefits to any research fund, foundation, educational
institution, or other charitable or nonprofit organization with which the
authors are affiliated or associated.