Case report of unilateral clefting: is sonic hedgehog to blame?

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.