De novo 3q13.13q21.2 interstitial deletion and paternal 12p13.3 microdeletion in a fetus with dysplasia of the corpus callosum and ventriculomegaly: A case report

Abstract

Chromosome 3q syndrome is a well-known genetic condition caused by interstitial deletion in the long arm of chromosome 3. The phenotype of this syndrome is variable and the great variability in the extent of these deletions leads to a wide spectrum of clinical manifestations. Terminal 12p deletion represents one of the rarest subtelomeric imbalances; patients with distal monosomy 12p present different phenotypes ranging from muscular hypotonia to autism spectrum disorders. The present study reported a prenatal diagnosis of a male fetus presenting ultrasound evidence of corpus callosum dysplasia and ventriculomegaly showing a 3q13q21.2 deletion and a 12p13.33 microdeletion paternally inherited. Among several features previously attributed to the terminal deletion of 3q, corpus callosum dysplasia and ventriculomegaly have rarely been reported together. As the 12p13.33 microdeletion in the father was associated only with muscular hypotonia and joint laxity, the involvement of terminal 12p deletions in the clinical features of the fetus was not possible to verify during the prenatal period. The present case report may provide a reference for prenatal diagnosis and genetic counseling in patients who present 3q13q21.2 deletions and 12p13.33 microdeletion.

Keywords: 12p13.3 microdeletion; 3q-syndrome; 3q13.13q21.2 deletion; aCGH; corpus callosum dysplasia; cytogenetic; karyotype; muscular hypotonia; prenatal diagnosis; ventriculomegaly.

Figure 1

Ultrasound evidence of clinical features of fetus. (A) Red arrows show the corpus callosum dysplasia, which presents as thin. (B) Red arrows show the corpus callosum dysplasia, which is not clearly visible. (C) Axial view of fetal cerebral ventriculomegaly (yellow arrow). (D) Sagittal view of the fetal face shows a flat forehead and facial profile.

Figure 2

G-banded karyotype of fetus and relative ideogram showing the region of chromosome 3 harboring the 3q deletion.

Figure 3

The scatter plot of the array comparative genomic hybridization of the fetus. (A) The deletion at the region 3q13.13q21.2 is estimated to be 12.87 Mb (from 111162064 to 124034052 kb) harboring 81 OMIM genes. (B) The deletion at the region 12p13.33 is estimated to be 1.23 Mb (from 100698 to 1327097 kb) harboring 16 OMIM genes. OMIM, Online Mendelian Inheritance in Man.

Figure 4

Coding genes and graphical representation of 12 chromosome region (12p13.33) involved in microdeletion. The deletion at 12p13.33 detected in our patient is represented by a red box on chromosome. 12p13.33 microdeletion in our patient overlapping pathogenic/likely pathogenic deletions (red bars) in other cases present in the Decipher database (https://decipher.sanger.ac.uk/) presenting (A) hypotonia or (B) joint laxity.