Prenatal diagnosis of Nager syndrome in a 12-week-old fetus with a whole gene deletion of SF3B4 by chromosomal microarray

Abstract Less than one hundred cases of the acrofacial dysostosis, Nager syndrome, have been described. The cardinal features of Nager syndrome are micrognathia, midface retrusion and limb malformations, predominately of the radial ray of upper extremities. Within the past three years haploinsufficiency of SF3B4 has been confirmed as the major cause of Nager syndrome. Different loss-of-function point-mutations in SF3B4 have been found in approximately 2/3 of patients diagnosed with Nager syndrome. Whole gene deletions of SF3B4 have also been suggested to be the cause of Nager syndrome in SF3B4 point mutation negative patients. Only four prenatal cases displaying Nager-like features in the 2nd or 3rd trimester which have been genetically confirmed with SF3B4 point-mutation after birth have been described. We report a case of a 12-week-old fetus with micrognathia, malformed wrists, bilateral club foot and short long bones diagnosed prenatally by chromosomal microarray with a de novo 0.4 Mb deletion at chromosome 1q21.2 involving SF3B4. To our knowledge, this is the first report of Nager syndrome caused by a SF3B4 whole gene deletion. The case presented also shows that high-resolution chromosomal microarray in early pregnancy can confirm Nager syndrome caused by SF3B4-deletion prenatally.