Congenital malformations - Edocr

CHAPTER 46 SKELETAL DYSPLASIAS 309
Group 1: Defects in extracellular structural proteins
as in osteogenesis imperfecta, achondrogenesis,
and multiple-epiphyseal dysplasia
Group 2: Defects in metabolic pathways as in
hypophosphatasia, infantile osteopetrosis,
and chondrodysplasia punctata
Group 3: Defects in folding and degradation of
macromolecules as in pycnodysostoses, and
lysosomal storage diseases
Group 4: Defects in hormones and signal transduction
mechanisms as in achondroplasia,
thanatophoric dysplasia, hypochondroplasia,
and hypophosphatemic rickets
Group 5: Defects in nuclear proteins and transcription
factors as in camptomelic dysplasia,
and cleidocranial dysplasia
Group 6: Defects in oncogenes and tumor suppressor
genes as in multiple exostoses
syndrome
Group 7: Defects in RNA and DNA processing
and metabolism as in cartilage-hair-hypoplasia
CLINICAL PRESENTATION
The spectrum of clinical presentation in these
patients can range from early neonatal death
secondary to respiratory failure to a normalappearing
infant with only subtle findings of
disproportionate stature in the newborn period.
Table 46-1 summarizes the important clinical
features of common skeletal dysplasias presenting
in the perinatal period. The associated
anomalies of other organ systems are variably
present and can help in establishing diagnosis
in these patients.
EVALUATION
Evaluation of an infant suspected to have skeletal
dysplasia is often challenging because of a
wide range of differential diagnosis, rarity of
condition, and relative inexperience of physicians
providing care. An accurate diagnosis is
critical to make appropriate decisions regarding
medical care and counseling of parents. A
systematic approach is crucial and should include
the following steps:
1. History: A complete three generation family
history can provide important clues to
the diagnosis and should include history of
consanguinity, ethnicity, unexplained perinatal
deaths, recurrent fractures, short
stature, and early arthritis in other family
members. Maternal use of warfarins during
pregnancy is known to cause clinical picture
consistent with chondrodysplasia punctata.
History of exposure to other teratogens
such as alcohol, thalidomide, and maternal
history of phenylketonuria or diabetes mellitus
should also be asked.
2. Physical examination: The accurate anthropometric
measurements are important
in deciding if an infant has short stature for
gestational age and if it is proportionate or
disproportionate. In a normal infant, the fingertips
of the hand fall between the iliac
crest and upper one-third of the thigh; therefore
fingertips above the iliac crest would
suggest short-limbed short stature. An increased
upper segment to lower segment
(US/LS) ratio will confirm the presence of
disproportionate growth. The lower segment
is measured from the top of the symphysis
pubis to the sole of the foot and the
upper segment is obtained by subtracting
the lower segment value from the total
length. A normal US/LS ratio in the newborn
infant is 1.7. The measurement of arm
span, the distance between the fingertips of
the middle fingers of each hand with arms
stretched out horizontally is also helpful.
The normal arm span in an infant is about
2–3 cm less than the total length. US/LS ratio
is increased and arm span is decreased
in infants with short-limbed short stature
such as in achondroplasia but infants with
short-trunk short stature such as in spondyloepiphyseal
dysplasia will have a normal
arm span with reduced US/LS ratio. 3,13 The