a 29-year - old g2p1001 ( currently pregnant second time and had one previous full - term living child ) female was referred to the center for medical genomics at the magee womens hospital after the first trimester screening for down syndrome , adjusted for age , trisomy 21 risk of 1:16 , and a trisomy 18 risk of 1:49 . a three - generation family pedigree did not reveal history of birth defects , intellectual disability , or recurrent miscarriages . fetal ultrasound was performed at 13  weeks of gestation and demonstrated a simple fetal pelvic cyst measuring 12    7    9  mm and an enlarged fetal bladder . follow - up ultrasound at 16  weeks of gestation revealed a persistently enlarged , thick - walled fetal bladder , echogenic kidneys , bilateral pyelectasis measuring 6  mm in anterior to posterior direction for each kidney , two - vessel cord , septated cystic hygroma arising from the posterior neck , oligohydramnios with an amniotic fluid index ( afi ) of 53  mm , and thickened placenta at 31  mm ( fig.1 ) . amniocentesis performed at 16  weeks and 5  days of gestation showed a normal male karyotype . based on the presence of multiple fetal anomalies on ultrasound , fetal dna was extracted from the cultured amniotic fluid sample using the puregene genomic dna purification kit ( qiagen , valencia , ca ) , and studied by whole - genome oligonucleotide comparative genomic hybridization ( acgh ) microarray analysis using a custom 135  k feature platform ( designed by signature genetics laboratories , spokane , wa ; manufactured by roche nimblegen , madison , wi ) . array cgh analysis revealed a 12.57  million base pairs ( mb ) gain in the 6q25.3-qter region and a 12.24-mb loss within the 10q26.12-qter ( arr[hg18 ] 6q25.3q27(158,171,843 - 170,743,204)3 , 10q26.12q26.3(123,017,596 - 135,253,240)1 ( fig.2a and b ) . the 12.5-mb terminal 6q duplication caused trisomy for 46 omim genes , and the 12.2-mb terminal 10q deletion caused monosomy for 49 omim ( online mendelian inheritance in man database : www.omim.org ) genes . confirmatory fluorescence in situ hybridization ( fish ) analysis with 6q and 10q subtelomere - specific probes ( abbott molecular , des plaines , il ) showed a derivative chromosome 10 resulted from an unbalanced translocation between the distal 6q and 10q ( fig.2d ) . assessment of parental chromosomes 6q and 10q by fish analysis was normal , implying a de novo chromosomal abnormality in the fetus ( 46,xy.ish der(10)t(6;10)(q25.3;q26.12)(rp11 - 665c2+,rp11 - 702c24)dn . autopsy confirmed significant pyelectasis of one kidney with prominent glomerulocystic changes and dysplastic changes in the other kidney . a right foot talipes varus and bulbous tips of all digits were also present . ( a ) idiogram of chromosome 6 and microarray plot showing a 12.57  mb gain involving the distal 6q region ( pink - shaded area ) . ( b ) microarray plot demonstrating a deletion in the terminal long arm of chromosome 10 . top , idiogram of chromosome 10 with a deleted region shown by a red rectangle . below , a magnified view of the 10q26.12-qter terminal deletion ( blue shaded area ) . ( d ) fluorescence in situ hybridization ( fish ) analysis with a 6q subtelomere - specific probe ( red ) , showing an additional 6qter signal present on the derivative chromosome 10 . this study demonstrates a de novo chromosomal aberration involving a 12.57-mb duplication at 6q25.3-qter and a 12.24-mb deletion at 10q26.12-qter associated with multiple structural abnormalities on fetal ultrasound . this is the first prenatal case of 6q25.3-qter segmental trisomy diagnosed with the use of acgh . the resolution of karyotype analysis in prenatal diagnosis has historically been considered sufficient to detect chromosomal abnormalities in the 510  mb range . in our case , however , the 10q deletion and 6q duplication regions were greater than 10  mb and had seemingly normal g - banding patterns ( fig.2c ) . we present an example in which karyotype analysis failed to detect a derivative chromosome 10 , where a 12.24-mb 10q terminal segment has been replaced by a 12.57-mb segment from the terminal 6q . in our case , two rearranged segments are of similar size , 12  mb ; and both 6q25-q27 and 10q26.1-q26.3 segments embrace a single g - positive band , thus the exchanged chromosomal regions have similar g - banding pattern . therefore , a derivative chromosome 10 appeared to have the expected size and g - banding pattern as a normal chromosome 10 . multiple regions in human karyotype have similar banding patterns , and thus rearrangements involving alike segments will remain undetected even by high - resolution karyotype analysis , unless molecular technique such as acgh is used . pure trisomy of the distal 6q is a very rare event with only a few cases described in the literature . since the first description by de gouchy et  al . 1 common phenotypic features among children with 6q25-qter partial trisomy include cranial anomalies , facial dysmorphism ( slanting palpebral fissures , telecanthus , micrognathia , carp - shaped mouth ) , anterior webbing of the neck , cardiac anomalies , and joint contractures ; and profound psychomotor retardation 13 . prenatal diagnosis of trisomy 6q22.2qter was first reported in 1997 after ultrasound findings of cerebellar vermis , thick nuchal folds , bilateral hydronephrosis , ascites , bilateral clubfeet , distal arthrogryposis , atrial septal defect , patent ductus arteriosus , and ambiguous genitalia were identified 4 . partial deletion of the long arm of chromosome 10 is a relatively frequent cytogenetic finding . most cases of terminal 10q deletion have a breakpoint around 10q26 occurring either as de novo or as familial translocation with variable phenotypic features 5 . the most striking phenotypic features in patients with the 10q terminal deletions include facial dysmorphism ( microcephaly with prominent forehead , triangular face , down slanting palpebral fissures , coarse facial features , bilateral esotropia , epicanthic folds , synophrys , prominent nasal bridge , short philtrum , and small mouth ) , growth failure and developmental delay , intellectual disability , ophthalmoplegia , syndactyly , congenital cardiac , urinary , and anogenital anomalies , however , there is significant heterogeneity in the clinical presentation 5,6,9 . in our case , array comparative genomic hybridization ( acgh ) has been used to define the 600-kb critical region at 10q26 . this region includes dock1 and c10orf90 genes , thought to be important determinants of craniofacial , urogenital , and neuropsychiatric phenotypes 9 . the distal 10q region is known to be the critical for the internal and external development of the urogenital organs 7 . haploinsufficiency of pax2 ( 10q24.3-q25.1 ) , gfra1 ( 10q25.3 ) , and fgfr2 ( 10q26.12 ) genes was proposed to result in abnormal male genital development . terminal 10q deletions have also been associated with complete sex reversal and gonadal dysgenesis , imperforate anus , and ambiguous genitalia 8 . in our case , the 10q deletion caused haploinsufficiency for the fgfr2 gene and urinary tract abnormalities were observed , however , genitalia were not ambiguous and anogenital defects were not found on fetal ultrasound . ultrasound at 13 and 16  weeks detected structural defects , including urogenital abnormalities ( enlarged bladder , echogenic kidenys , bilateral pyelectasis ) , in addition to the septated cystic hygroma , consistent with features seen in patients with terminal 6q25-qter duplications and 10q26-qter deletions . in prenatal diagnosis , microarray analysis can unambiguously detect chromosomal imbalances and has substantial advantages by overcoming the limitations of resolution and banding quality that are inherent in conventional karyotype analysis 1012 . most microarray findings have been correlated with postnatal phenotypes , and there is a distinct need to build a database of microarray findings with prenatal ultrasound phenotyping . our case demonstrates the utility of microarray in detecting a complex chromosomal imbalances that presented with nonspecific findings of fetal pelvic cyst and an enlarged fetal bladder in the first trimester followed by second trimester ultrasound that detected thick - walled fetal bladder , echogenic kidneys , bilateral pyelectasis , two - vessel cord , septated cystic hygroma arising from the posterior neck , and oligohydramnios . facial dysmorphism , ambiguous genitalia , joint contractures , cardiac abnormalities , and syndactyly were not detected in our case . the use of acgh in prenatal diagnosis can elucidate the genetic etiology in fetuses with ultrasound abnormalities and enable proper genetic counseling , management of prenatal care , and informed decision making . the differences that can be observed in pre- and postnatal phenotypes are important for counseling and further studies regarding phenotypic variability and genotype . moreover , there is a distinct lack of genotype  phenotype correlation between individual microarray findings and this case report will add to the emerging atlas of chromosomal abnormalities associated with specific prenatal ultrasound findings .
key clinical messagewe present the prenatal case of a 12.5-mb duplication involving 6q25-qter and a 12.2-mb deletion encompassing 10q26-qter diagnosed by acgh , while conventional karyotype showed normal results . 
 the genotype  phenotype correlation between individual microarray and clinical findings adds to the emerging atlas of chromosomal abnormalities associated with specific prenatal ultrasound abnormalities .