Congenital Upper Limb Anomalies 179Valproic Acid (VPA)
VPA is an anticonvulsant used to treat seizures and manic depression. The
mechanism of action surrounding the teratogenic effects of VPA is unclear.
Paradis and Hales hypothesized that VPA disrupts regulation of the expression
of genes that are critical in chondrogenesis and osteogenesis during limb
development. They tested this in mouse forelimbs and found it to be true as
there was a downregulation in expression of RUNX2 and SOX9 (Paradis and
Hales, 2013). Analysis of a case-control study done on data from Spanish
Collaborative Study of Congenital Malformations (ECEMC) assessed the
relationship between prenatal exposure to VPA and the presence of limb
deficiencies in newborn infants. Of the total of malformed infants exposed to
VPA, 36.8% (21/57) presented with congenital limb defects of different types,
including overlapping digits, clubfoot, clinodactyly, arachnodactyly, pre- and
postaxial polydactyly (Rodriguez-Pinilla et al., 2000).
Retinoic Acid
In very high doses, retinoic acid (a derivative of Vitamin A) may affect
limb development. Isotretinoin, which is closely related to Vitamin A, is used
by some as a treatment for severe acne. Isotretinoin (sold under several brand
names, including Accutane) has been linked to birth defects and is not advised
for women who are pregnant or who may become pregnant while taking the
medicine.
Recreational Drugs
Alcohol
Alcohol is a common drug abused by women of childbearing age. Infants
born to alcoholic mothers demonstrate prenatal and postnatal growth
deficiency, mental retardation, and other malformations, including those of the
limb (Spiegel et al., 1979; Herrmann et al., 1980; Cremin and Jaffer, 1981; van
Rensburg, 1981). In the early 1970’s a link between maternal alcohol intake
and congenital upper limb anomalies was observed and Spiegel et al., reported
the most frequent malformation associated with Fetal Alcohol Syndrome
(FAS) is radioulnar synostosis (Spiegel et al., 1979). This group also reported
that hypoplastic toenails, shortened fingers, camptodactyly of the fingers,
clinodactyly of the toes, and flexion contractures of the elbow are observable
phenotypes of FAS.