Defect in dorso-ventral patterning in a spontaneously aborted foetus

Abstract

We report on a spontaneously aborted 13-week male foetus, born with a reversed orientation of the head and upper limb relative to the rest of the body. The head and both upper limbs were facing dorsally while the lower limbs, the abdomen and the thorax were in their normal orientation. The vertebral column was abruptly rotated through 1800 at the level of the seventh cervical vertebrae. The clavicles were in their normal positions, and the scapulae were located dorsally while the arms and forearms were directed posteriorly with the elbow flexure directed caudally and the preaxial border directed cranially. The left palm was facing medially, whereas the right palm was facing laterally. The orientation of the right upper limb was equivalent to a medial rotation through 1800 at the shoulder joint, while the left upper limb appeared to be a replica of the right upper limb. In addition, the right hand was dorsiflexed at the wrist, while the left hand had a short 2nd digit with absence of the middle and distal phalanges. Both lower limbs had talipes calcaneovalgus. The heart showed a conotruncal defect and single ventricle. The spleen was absent. The other viscera were normal. We interpret this abnormality as a field defect of dorso-ventral patterning of the cranial part of the trunk and upper limb buds, affecting also septation of the outflow tract and ventricle, which develop embryologically in the cervical region. Dorso-ventral differentiation is regulated by Wnt-7a, a member of the Wnt family, which induces the expression of Lmx-1, a Lim homeobox gene that may be responsible for dorsalization of limb buds.