Case Report of Unilateral Clefting: Is Sonic Hedgehog to Blame?

Abstract

We describe the autopsy of a chromosomally normal multiple-anomaly fetus with left side–restricted malformations, terminated after routine screening ultrasound. Autopsy findings were remarkable for severe left-sided craniofacial malformations including a cleft left frontal calavarial bone and an oblique facial cleft. Internal examination showed multiple left-sided malformations including severe left ventricular hypoplasia and interrupted aortic arch. A hypoplastic left lung, an accessory spleen, and an absent left kidney and left ureter were also discovered. Some features of the Smith-Lemli-Opitz Syndrome (SLOS) are found in this fetus, yet the occurrence of left side–restricted anomalies indicates that developmental mechanisms responsible for body laterality are involved. Potential mechanisms leading to this constellation of anomalies include a ciliary defect, side-restricted chromosomal mosaicism, or a teratogenic insult, affecting developmental morphogens, including sonic hedgehog. The sonic hedgehog pathway is important in the molecular mechanisms underlying SLOS and in laterality development in the early embryo.