Congenital malformations - Edocr

316 PART VIII SKELETAL MALFORMATIONS
3. Radiologic evaluation: The radiologic evaluation
has been extremely helpful in establishing
a diagnosis in these infants. The skeletal
survey in these infants should include: frontal
and lateral views of vertebral column, lateral
views of the cervical spine and skull, anteroposterior
views of chest and pelvis, and anteroposterior
views of one upper and one
lower extremity. In cases with limb asymmetry,
it may be necessary to obtain views of
both upper and lower limbs. Imaging of other
family members suspected of having the same
condition as the proband may be helpful.
Serial skeletal surveys may be necessary when
the diagnosis is not certain on initial evaluation
but repeating the survey earlier than 12 months
of initial survey is not likely to be helpful. 4
These films are most helpful when reviewed
by a pediatric radiologist with interest and experience
in this area. Table 46-3 summarizes
the important radiological findings in skeletal
dysplasias commonly presenting in the
perinatal period.
4. Laboratory evaluation: Serum calcium,
phosphate, and alkaline phosphatase levels
should be measured and are more helpful in
infants with abnormal mineralization of the
bones. The peroxisomal testing and sterol
profile may be helpful in infants with stippled
epiphyses. Histopathological evaluation
of chondro-osseous tissue can be particularly
helpful in patients with no clear diagnosis
based on clinical and radiological evaluation.
Testing for mutations in collagen genes can
be helpful in osteogenesis imperfecta.
5. Genetic testing: A karyotype should be
carried out if there are associated malformations
of other organ systems and it can
be particularly helpful in the diagnosis of
camptomelic dysplasia in which a 46XY infant
frequently has a female phenotype on
examination. Molecular diagnosis utilizing
DNA studies has become possible for most
of these disorders but may not be easily
available or be practical in many cases.
Blood samples and fibroblast cultures from
skin biopsy or placental tissue can be stored
to allow DNA analysis at a later date.
Figure 46-1 provides a systematic approach
to arrive at a diagnosis in infants with
common skeletal dysplasias presenting in
the perinatal period.
PROGNOSIS
Skeletal dysplasias are frequently classified as
lethal or nonlethal. Lethality of a particular diagnosis
is mainly related to the associated pulmonary
hypoplasia from an abnormally formed
restrictive thorax. The cause of death in some
others could be related to respiratory failure
secondary to brainstem compression due to
the stenosis of foramen-magnum or secondary
to severe airway anomalies. Several studies have
evaluated the ability of prenatal ultrasound findings
to predict the neonatal outcome of affected
fetuses. Although only 48–65% of specific diagnoses
are correct, the identification of a lethal
dysplasia is highly accurate. 11 The following
criteria have been used to diagnose lethal skeletal
dysplasia on prenatal ultrasound: (1) early
severe micromelia; (2) femur length: abdominal
circumference