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INTRODUCTION

Case 1: Ms. Sanfilippo is a 25-year-old gravida 5 para 3104 whose first-trimester screen gave her a 1:1200 risk of Down syndrome and <1:5000 risk of trisomy 18, and a second-trimester alpha fetoprotein was in the normal range (1.2 MOM). She has no significant past medical history. Her obstetric history was significant for a previous term spontaneous vaginal delivery complicated by a rectovaginal fistula. This was followed by a term cesarean delivery, and her last pregnancy was a preterm repeat cesarean at 34 weeks. A three generation family history was significant for Hirschsprung disease in a son with a previous partner. An initial anatomy ultrasound at 18 weeks of gestation was performed at an outside hospital, and showed the fetus to have a left sided diaphragmatic hernia with cardiac displacement to the right side of the chest. The patient was referred to a regional center because of the abnormal ultrasound. A repeat ultrasound at 20 weeks of gestation identified a thickened nuchal fold of 7 mm, bilateral echogenic kidneys with nephromegaly, and a left-sided diaphragmatic hernia. Ms. Sanfilippo was counseled about the risks and benefits of amniocentesis. Rapid FISH analysis was performed on 50 interphase cells from the amniotic fluid with #13, #18, #21, X-, and Y-specific probes. No evidence of trisomy 13, 18, or 21 was detected. Analysis of the X and Y probe revealed two copies of the X probe and no copies of the Y probe, consistent with 46,XX female karyotype. FISH analysis was also performed using probes specific for chromosome 12 to rule out mosaic isochromosome 12p (Pallister-Killian syndrome), and the results were consistent with normal chromosome 12. Fifteen cells were analyzed from the amniotic fluid specimen. No significant numerical or structural aberrations were seen at the 475 G-band level of resolution. The karyotype was reported as normal, 46,XX female. Since the karyotype and FISH results were both normal, an oligonucleotide microarray was performed. Microarray-based comparative genomic hybridization (aCGH), also known as chromosomal microarray technique (CMA) was performed using a 135K-feature whole-genome microarray. Microarray revealed a 1.4-Mb deletion on 17q12. Neither parent carried the deletion; therefore this deletion was a de novo finding. The deletion caused haploinsufficiency for 17 genes, including AATF, ACACA, DDX52, DUSP14, GGNBP2, HNF1B, LHX1, PIGW, SYNRG, TADA2A, and ZNHIT3. The deleted region on 17q12 is similar in size and gene content to the previously reported 17q12 microdeletion syndrome.1 The 17q12 microdeletion syndrome has been associated with MODY5 (maturity-onset of diabetes of the young, type 5), cystic renal disease, pancreatic atrophy, liver abnormalities, cognitive impairment, and structural brain abnormalities. Ms. Sanfilippo was counseled with regards to the diagnosis and prognosis. The risk of recurrence is at most 2% to 3%, as gonadal mosaicism cannot be ruled out. After reviewing the risks and prognosis associated with congenital diaphragmatic hernia and 17q12 microdeletion syndrome, Ms. Sanfilippo opted for comfort measures after her baby is born.

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