Prenatal diagnosis of inverted duplicated 8p

Abstract

The phenotype of inverted duplicated 8p, region 8p11.2-p23, reported in children and adults, includes: severe mental retardation, minor facial anomalies, agenesis of corpus callosum, and other malformations including those of heart and kidneys. We report on the prenatal diagnosis of 2 cases of inverted duplication 8p. Both cases were ascertained by abnormal level 2 ultrasound findings. Case 1 presented at 16.5 weeks of gestation with massive distention of the fetal bladder, bilateral hydronephrosis, abnormality of the lower lumbar spine, absence of the sacral spine and a Dandy-Walker variant (interhemispheric cyst and enlarged third ventricle). Case 2 presented at 30 weeks of gestation with agenesis of corpus callosum, slightly enlarged lateral ventricles, interhemispheric cyst and enlarged third ventricle, and possible coarctation of the aorta. The intracranial and cardiac anomalies were confirmed and further defined after delivery. Cytogenetic analysis in both cases showed additional material on 8p. In both cases, fluorescence in situ hybridization (FISH) defined the abnormal chromosome, as a pseudodicentric chromosome with duplication of the short arm from centromere to p23 and deletion from p23 to pter. Our findings support those of prior reports of the inverted duplicated 8p chromosome with multiple anomalies and add prenatal findings to our knowledge.

Fetoplacental discrepancy involving structural abnormalities of chromosome 8 detected by prenatal diagnosis

“…To our knowledge, this is the third report of a prenatally detected inv dup(8) (MacMillin et al, 2000) and the first to include discrepant rearrangements of chromosome 8 in chorionic villi versus amniocytes. The present case discloses the importance of the information that can be obtained from placental tissue in order to interpret the formation of structural chromosome rearrangements.…”

“…Structural mosaicism is a rare event and is often difficult to interpret. Different structural rearrangements of chromosome 8 have been reported; among them inv dup(8p) is a recurrent finding (de Die-Smulders et al, 1995;Guo et al, 1995;Floridia et al, 1996;Kotzot et al, 2000;Tonk et al, 2001;Giglio et al, 2001) and has been diagnosed prenatally (MacMillin et al, 2000). The present report describes the prenatal diagnosis of a mosaic for isochromosome 8q and a deletion of 8p found in chorionic villi cells and an inv dup(8p) in amniocytes, and proposes a model to explain the cytogenetic discordance between the placenta and the fetal tissues.…”

“…The unexpected karyotype obtained was 46,XX,dup(8)(p23p11.2) de novo. Since this inverted duplication of 8p has been reported to be associated with brain malformations, severe mental retardation and multiple minor anomalies (reviewed by de Die-Smulders et al, 1995;MacMillin et al, 2000), the pregnancy was terminated at 18 weeks. Pathologic findings included clubfeet, clenched left hand, subcutaneous edema and bilateral hydrocephalus.…”

Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases

“…Previously reported cases in this region include anomalies of the central nervous system, renal and cardiac systems [4]. Patients with this duplication also present with severe intellectual disability and multiple minor abnormalities [5]. The patient declined further genetic testing for herself and partner and elected to continue the pregnancy.…”

Genomic profile of copy number variants on the short arm of human chromosome 8

“…[2][3][4][5][6] These REPD-and/or REPP-related 8p genomic rearrangements include (1) the 8p23.1 deletion or duplication between REPD and REPP, [6][7][8][9] (2) the 8p23.1 paracentric inversion between REPD and REPP, 8,10 (3) the pericentric inversion (inv(8)(p23.1q22.1)) and recombinant chromosome 8 (rec (8)dup(8q)inv(8)(p23.1q22.1)), 11 (4) the 8p interstitial inverted duplication with associated terminal deletion (inv dup del(8p)), 5,6,8,10,[12][13][14][15][16][17][18][19][20][21][22][23][24] (5) the 8p translocations involving the 8p23.1, 25,26 and (6) different types of supernumerary chromosome 8 (SMC (8)) involving the breakpoints within 8p23.1. 4,27 In addition to these defined 8p genomic abnormalities, other pathogenic genomic changes have been identified, [28][29][30] whereas numerous genomic imbalances on 8p are still described as copy number variants (CNVs) of unknown clinical significance or CNVs without apparent clinical significance (benign CNVs) (http://projects.tcag.ca/variation).…”