Genotype–phenotype correlation and pregnancy outcomes of partial trisomy 14q: A systematic review

Abstract

Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc.

Two Abnormal Cell Lines of Trisomy 14 and t(X;14) with Skewed X-Inactivation

“…Aside from cognitive impairment and severe postnatal growth retardation, developmental brain malformations have been reported occasionally with trisomy 14 mosaicism. Our patient shares the agenesis of the corpus callosum and vermis cerebellar hypoplasia with dilated 4th ventricle with few reports [Tunca et al, 2000;Lynch et al, 2004;He et al, 2014;Bregand-White et al, 2016]. In addition only one study described lissencephaly [He et al, 2014].…”

“…It appears that they all share recognizable clinical features although of variable severity, such as intellectual disability, growth impairment, dysmorphic facial features (prominent forehead, down-slanting palpebral fissures, hypertelorism, a depressed nasal bridge, low-set malformed ears, a long philtrum, micrognathia, and cleft palate), body asymmetry, skin hyperpigmentation, congenital heart disease, and urogenital anomalies. The clinical severity of the reported cases with trisomy 14 does not seem to be influenced by the size of the trisomic region [Bregand-White et al, 2016] but could rather be the percentage of the trisomic cells [He et al, 2014]. Some authors have attracted the attention to the influence of the uniparental disomy on the phenotype of trisomy 14 mosaicism [Salas-Labadía et al, 2014;Suzumori et al, 2015].…”

“…By this method we can expect to diagnose many genetic disorders with very small chromosome copy number variance, mosaic cell lines (array-CGH is not sensitive enough to detect the low percentage of mosaic cell line), and the possibility for diagnosis of recessive disorders in regions of LOH by SNP array analysis [Conlin et al, 2010;Chen et al, 2019]. Bregand-White et al [2016] gave evidence that patients with partial trisomy 14 usually show postnatal growth failure regardless of the parental origin, while those with severe intrauterine growth retardation are more frequently associated with maternal disomy. Nevertheless, they develop truncal obesity thereafter [Ioannides et al, 2014;Zhang et al, 2016;Kagami et al, 2017;Ushijima et al, 2018].…”

“…These 2 events may have happened separately or maybe there is a kind of trisomy or monosomy rescue due to dynamic cytogenetic interaction between different cell lines to compensate for gene dosage. © 2020 S. Karger AG, Basel While complete trisomy of chromosome 14 is lethal, more than 50 patients with partial or complete mosaicism of trisomy 14 have been reported to date [Bregand-White et al, 2016]. Complete trisomy 14 mosaicism could be attributed to either maternal or paternal nondisjunction or postzygotic errors, while partial trisomy usually results most commonly in balanced translocation carriers or is due to de novo intrachromosomal 14q duplications.…”

Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3

“…Fluorescence in situ hybridization (FISH) analysis for chromosomes 13, 18, 21, X, and Y was performed on uncultured amniotic fluid cells using Aneuvysion kit according to the manufacturer's instructions (Abbott Laboratories, Des Plaines, IL; DAKO/Agilent Santa Clara, CA). G‐banded karyotypes were studied following routine protocol on cultured amniotic fluid cells and peripheral blood samples from both parents, as previously described (Bregand‐White et al, ). The DNA sample was extracted from cord blood.…”