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.
Delaney
Meghan
M
Beth Israel Deaconess Medical Center, Department of Pathology, 330 Brookline Avenue, Boston, MA 02215, USA. mdelaney@pipeline.une.edu
Boyd
Theonia K
TK
D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D000028:Abortion, Induced; D001842:Bone and Bones / Q000473:pathology*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012886:Skull; D019082:Smith-Lemli-Opitz Syndrome / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016216:Ultrasonography, Prenatal
D053823:Hedgehog Proteins; C509239:SHH protein, human