Review Question - QID 216492

This patient with ventricular septal defects (harsh holosystolic murmur), radial arm patterning abnormalities, and extra-thoracic ribs most likely has a defect in Hox (homeobox) gene expression.

Homeobox genes are a set of differentiation genes involved in the segmental organization of the body in a cranial to caudal direction. Differential expression of these genes in different segments during embryologic development allows for each segment to assume a different role. For example, the expression of Hox genes by the zone of polarizing activity in the arm allows for radioulnar differentiation. Similarly, selective expression of certain Hox genes in the thorax allows for rib formation. Abnormalities in Hox gene expression results in abnormal patterning of the body during embryologic development.

Miksiunas et al. discuss how homeobox gene expression usually manifests early in life with cardiac abnormalities. The mechanisms by which each gene leads to specific defects are unclear, and further research is needed to understand patterning defects.

Incorrect Answers:
Answer 1: Fgf (fibroblast growth factor) is responsible for the production of fibroblast growth factor, which stimulates mitosis and differentiation of mesodermic derivatives. This gene is produced at the apical ectodermal ridge and is responsible for the lengthening of limbs rather than radioulnar patterning.

Answer 3: Lmx (LIM homeobox transcription factor) is responsible for the production of LIM-homeodomain factor, which is responsible for dorsal to ventral patterning of the upper extremity. For example, Lmx is needed for nail development exclusively on the dorsal side of the hand.

Answer 4: Shh (sonic hedgehog) is responsible for the production of sonic hedgehog factor, which is also involved in the radioulnar patterning of the forearm; however, associated defects of Shh abnormalities involve holoprosencephaly and gut formation rather than cardiac and rib formation.

Answer 5: Wnt (wingless int) is responsible for the production of wingless proteins, which are involved in midbrain development as well as dorsal to ventral patterning of the limbs.

Bullet Summary:
Hox genes are responsible for craniocaudal development, and defects result in cardiac, limb, and rib abnormalities.