Diagnostic ultrasound ( PDFDrive )

CHAPTER 40 The Fetal Musculoskeletal System 1391
Achondrogenesis
Achondrogenesis is the second most common lethal skeletal
dysplasia, with a prevalence of 0.09 to 0.23 per 10,000 births. It
is a phenotypically and genetically diverse group of chondrodysplasias
characterized by severe micromelia, macrocranium,
decreased thoracic circumference and trunk length, and
decreased mineralization. 64,65 he pattern of abnormal mineralization
is most marked in the vertebral bodies, ischium, and
pubic bones, leading to a greatly shortened trunk length, decreased
thoracic circumference, and occasional fractures. 66 Classically,
because of abnormal skeletogenesis of the vertebral body, only
the two echogenic posterior elements or neural arches appear
in a transverse image of the spine. his is in contrast to hypophosphatasia,
which predominantly involves the posterior
elements in the spine with only patchy involvement of the vertebral
bodies. Polyhydramnios and thick, redundant skin folds are a
common accompaniment of achondrogenesis. 67
Type 1 achondrogenesis accounts for about 20% of cases and
is divided into A and B subtypes (ACG1A and ACG1B). 7,65 ACG1A
includes rib fractures, which are not present in ACG1B. Both
have autosomal recessive mode of inheritance and thus have a
25% recurrence risk. ACG1A is caused by mutations in TRIP11,
while ACG1B is caused by mutations in the diastrophic dysplasia
sulfate transporter gene. Both ACG1A and ACG1B have a severe
form of micromelia, evidenced by short, cuboid bones and
metaphyseal scalloping with bone spurs at the periphery. Other
indings include partial or complete lack of ossiication of the
calvarium, vertebral bodies, and sacral and pubic bones. Because
of the extremely limited skeletal frame, the subcutaneous tissues
can appear grotesquely redundant, with multiple telescoped skin
folds that may be mistaken prenatally for hydrops fetalis.
Type 2 (AGH2), or the Langer-Saldino form, accounts for
80% of achondrogenesis cases. It is caused by a new dominant
mutation in the COL2A1 gene that encodes type II collagen and
carries a low recurrence risk. It is characterized by normal calvarial
ossiication and by absent ossiication in the vertebral column
and sacral and pubic bones (Fig. 40.16). ACG2 has the least
ossiication of the vertebral column of all the skeletal dysplasias.
he type 2 collagen disorders represent a continuous spectrum
from lethal to mild. It may be diicult to come to a irm conclusion
about lethality. In general, relatively longer tubular bones and
body length are associated with increased survival. Hypochondrogenesis
is phenotypically similar to ACGE and usually lethal
but radiologically less severe with better ossiication of the spine,
pelvis, and long bones. Another condition to diferentiate is
Kniest dysplasia, characterized by vertebral coronal clets and
metaphyseal expansion (most prominent in the proximal femurs). 2
hese two key features of achondrogenesis—abnormal
mineralization and shortened trunk length—distinguish it from
thanatophoric dysplasia, which has normal mineralization and
a normal trunk length. Both display macrocrania and severe
micromelia.
Osteogenesis Imperfecta
OI is a clinically and genetically heterogeneous group of collagen
disorders characterized by brittle bones resulting in fractures
(Figs. 40.17 and 40.18). he incidence is 1 in 60,000 births. Until
recently there were four clinical types of OI, all with an autosomal
dominant mode of inheritance and associated with mutations
in the COL1A1 or COL1A2 genes. Type II OI is lethal, whereas
the other types are milder. In the past several years, many new
causative genes have been identiied. 68,69 Most are involved in
the complicated process of maturation, processing, and transport
R
A
B
FIG. 40.16 Achondrogenesis at 18 Weeks. (A) Coronal sonogram shows small thorax, redundant subcutaneous tissues, absent spine ossiication
(arrows), and decreased calvarial ossiication. (B) Postmortem radiograph demonstrates macrocranium, decreased calvarial ossiication, virtually
absent spine ossiication (only some posterior elements are ossiied in the cervical region). There is severe micromelia with strikingly short wide
bones with metaphyseal spurs. The ribs are short and horizontal with splayed ends. (Courtesy of Shia Salem, MD, University of Toronto.)