Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with congenital diaphragmatic hernia: a case report

Genesio, Rita; Maruotti, Giuseppe Maria; Saccone, Gabriele; Mormile, Angela; Conti, Anna; Cicatiello, Rita; Sarnataro, Viviana; Sirico, Angelo; Izzo, Antonella; Martinelli, Pasquale; Nitsch, Lucio

doi:10.1002/ccr3.1369

Cited by 9 publications

(4 citation statements)

References 16 publications

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“…16p11.2 microdeletion manifests a wide variety of phenotypes, including neurodevelopmental disorders such as ASD, ID, behavioral disorders, seizures/epilepsy, and hypotonia, as well as congenital malformations of the spine, brain, and cardiovascular system, such as macrocephaly and Chiari I/cerebellar tonsillar ectopia (Bernier et al, 2017;Jacquemont et al, 2011;LeBlanc & Nelson, 2016;Steinman et al, 2016). Another case report showed a rare association with congenital diaphragmatic hernia (Genesio et al, 2018). Some of the symptoms discovered in microdeletion syndrome are also seen in duplication cases and include speech articulation abnormalities, hypotonia, abnormal agility, and seizures/epilepsy (Steinman et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants

Kang

Lee

et al. 2023

Molec Gen & Gen Med

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Background The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. Methods We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. Results Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. Conclusion Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 99%

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants

Kang

Lee

et al. 2023

Molec Gen & Gen Med

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“…Worthy of attention in the prenatal setting are CNVs predisposed to neuro-developmental disorders (i.e., CNVs with incomplete penetrance and variable expressivity) [6]. Variants in the 16p11.2 region can be associated with neuro-developmental disorders including autism spectrum disorders, schizophrenia, intellectual disability, microcephaly, facial dysmorphism [6,14], and obesity [15], even though 16p11.2 duplications or deletions can also be found in asymptomatic carriers [16]. Since the neuro-developmental phenotype cannot be determined in the prenatal setting, these CNVs raise significant challenges for genetic counseling.…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency

et al. 2019

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We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis.

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“…The small cohorts are a limitation of the present study and also the large age span as mentioned previously might be a limitation if you regard that as different phenotype severity. Thus further genetic studies on larger cohorts are necessary to fully understand the impact of rare CNVs in intestinal malrotation, as aCGH is a powerful tool to identify disease‐causing genes in both isolated and syndromic gastrointestinal malformations (Dworschak et al, ; Genesio et al, ; Tsai et al, ).…”

Section: Discussionmentioning

confidence: 99%

Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation

Karlslätt

Pettersson

Jäntti

et al. 2019

Molec Gen & Gen Med

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Background Intestinal malrotation is a potentially life‐threatening congenital anomaly due to the risk of developing midgut volvulus. The reported incidence is 0.2%–1% and both apparently hereditary and sporadic cases have been reported. Intestinal malrotation is associated with a few syndromes with known genotype but the genetic contribution in isolated intestinal malrotation has not yet been reported. Rare copy number variants (CNVs) have been implicated in many congenital anomalies, and hence we sought to investigate the potential contribution of rare CNVs in intestinal malrotation. Methods Analysis of array comparative genomic hybridization (aCGH) data from 47 patients with symptomatic intestinal malrotation was performed. Results We identified six rare CNVs in five patients. Five CNVs involved syndrome loci: 7q11.23 microduplication, 16p13.11 microduplication, 18q terminal deletion, HDAC8 (Cornelia de Lange syndrome type 5 and FOXF1 ) as well as one intragenic deletion in GALNT14 , not previously implicated in human disease. Conclusion In the present study, we identified rare CNVs contributing pathogenic or potentially pathogenic alleles in five patients with syndromic intestinal malrotation, suggesting that CNV screening is indicated in intestinal malrotation with associated malformations or neurological involvements. In addition, we identified intestinal malrotation in two known syndromes (Cornelia de Lange type 5 and 18q terminal deletion syndrome) that has not previously been associated with gastrointestinal malformations.

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Prenatally diagnosed distal 16p11.2 microdeletion with a novel association with congenital diaphragmatic hernia: a case report

Cited by 9 publications

References 16 publications

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants

Clinical outcomes of fetuses with chromosome 16 short arm copy number variants

Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency

Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation

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