Congenital malformations - Edocr

300 PART VIII SKELETAL MALFORMATIONS
3. Preaxial longitudinal: absence or hypoplasia
of preaxial (radial/tibial) part of
the limb.
4. Postaxial longitudinal: absence or hypoplasia
of postaxial (ulnar/fibular) part of
the limb.
5. Split hand/foot: longitudinal terminal deficiency
of rays, often associated with syndactyly.
a. Typical split hand/foot: a cone-shaped
cleft tapering and dividing the hand/foot
into two parts; absence or hypoplasia of
central ray (second, third, and fourth
fingers/toes); the phalanges or metacarpal/
metatarsal of the central rays may be
missing or reduced.
b. Monodactyly: merely one finger (deficiency
of four fingers) in either hand or
foot.
6. Multiple type of reduction defects: include
infants with different types of limb reduction
defects in one limb or different limbs.
EPIDEMIOLOGY/ETIOLOGY
The overall prevalence of limb reduction defects
is reported to vary from 2.5 to 7.06 per
10,000 births in several population-based registries.
2–7 These variations in the reported
prevalence are probably related to differences
in definitions, case ascertainment, inclusion of
stillbirths and pregnancy termination in some
studies; and effect of environmental/genetic factors.
In a study of nearly three million newborn
infants from South America, Castilla et al reported
the overall prevalence rate of limb reduction
defects as 4.91 per 10,000 live births
and 26.73 per 10,000 for stillbirths. 8 Nearly 40%
of live births and 80% of stillbirths with limb reduction
defects had associated congenital malformations.
8 Since the thalidomide tragedy in
the early 1960s, no significant changes in the
prevalence over time have been reported in
most studies. 3,4 Infants with limb reduction defects
are likely to have lower birth weight,
lower gestational age, and intrauterine growth
restriction (IUGR). These differences are more
prominent in infants with limb reduction defects
and other associated malformations. 4,6,7 No sex
differences were reported in most studies but a
slight male preponderance has been reported
by others. In a report from China, the prevalence
of limb reduction defects in rural areas
was reported to be significantly higher than in
urban areas. 7 Other reported risk factors are
vaginal bleeding and threatened abortion in the
index pregnancy. 9,10 A history of skeletal anomalies
among first degree relatives is reported in
6.5–7.2% of all patients with limb reduction defects.
7,9,11 The relationships between maternal
age, ethnicity, and risk of limb reduction defects
have not been consistent.
Limb reduction defects are a diverse group
of birth defects which could be a result of errors
in the genetic control of limb development, disruption
of normal development by a teratogen,
or intrauterine amputation of a normally developing
limb. 5 McGuirk et al reported that the apparent
causes of limb reduction defects in their
population were genetic or teratogenic in 34%,
vascular disruption in 35%, and unknown in the
remaining 32% of the cases. 5 Chromosomal abnormalities
have been reported in 6–13% of cases
and single gene disorders have been identified
in 15–43% of cases in other studies. 5,6,11,12 Amniotic
disruption sequence was reported as single
most common cause of limb reduction
defects by Evans et al. 4 A significant proportion
of all limb reduction defects occur sporadically
and no specific cause can be ascertained in many
of these cases.
An increased incidence of limb reduction
defects has been reported among infants of diabetic
mothers, and after intrauterine exposure to
alcohol, misoprostol, warfarin, phenytoin, valproic
acid, and retinoic acid, but none of these
associations have been proven conclusively. 13,14
A higher incidence of limb reduction defects is
observed in infants born to mothers who have
undergone chorionic villous sampling in early
pregnancy with the highest risk observed when
procedures were performed prior to nineth