8q21.11 microdeletion in two patients with syndromic peters anomaly

Happ, Hannah C; Schilter, Kala F.; Weh, Eric; Reis, Linda M.; Semina, Elena V.

doi:10.1002/ajmg.a.37840

Cited by 19 publications

(16 citation statements)

References 23 publications

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“…Most patients were reported to be neurologically abnormal, mainly characterized by developmental delay, intellectual disabilities, or autism spectrum disorder [26,27], contributing to 1q21.1 duplication syndrome; congenital heart defect was less commonly observed [28]. One fetus with CoA, VSD, increased spine curvature, and FGR revealed a 7. features [29,30], and congenital heart defects have also been rarely reported [31]. The fetus in our study died in utero at 34 gestational weeks, with no obvious abnormalities in the appearance of the delivered fetus.…”

Section: Discussionsupporting

confidence: 47%

Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype

Liu

et al. 2020

Mol Diagn Ther

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Background Aortic arch abnormalities (AAA) are abnormal embryologic developments of the aorta and its branches. Their outcomes often depend on their association with other congenital diseases and genetic testing results. Objective This study aimed to evaluate the yield of chromosomal microarray analysis (CMA) in fetuses with different patterns of AAA and normal karyotype. Methods Data from 158 pregnancies referred for prenatal CMA testing due to fetal AAA were obtained between April 2016 and April 2019. Fetuses with isolated AAA, AAA accompanied by soft ultrasound markers, and AAA with other ultrasound malformations were classified into groups A, B, and C, respectively. Cases with detectable karyotype aberrations were excluded from the study. Results Twenty cases (12.7%) of submicroscopic anomalies were detected in 158 cases with normal karyotype, comprising 16 cases (10.1%) of clinically significant variants, two cases (1.3%) of variants of unknown significance, and two variants (1.3%) that were likely benign. Microdeletion of 22q11.2 accounted for 25% (4/16) of the clinically significant variants. The overall incremental yields by CMA in group A, group B, and group C were 1.8%, 2.3%, and 24.1%, respectively. Except for double aortic arch, the incremental yield of clinical significant findings for each type of AAA in group C was much higher than that in group A and group B. In group A, a clinically significant variant was only detected in one fetus with right aortic arch (RAA) (1.8%, 1/57). Conclusions In addition to 22q11.2 microdeletion, many other clinically significant submicroscopic variants are present in fetuses with AAA, especially in fetuses with other ultrasound malformations. Although CMA is always recommended in the presence of any malformation in many countries, our results suggest insufficient evidence to recommend CMA in fetuses with isolated AAA, except for isolated RAA.

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Section: Discussionsupporting

confidence: 47%

Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype

Liu

et al. 2020

Mol Diagn Ther

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“…identified, including 8q21 deletions and pathogenic variants in TFAP2A, FLNA, PAX6, PITX2, CYP1B1, FOXC1, and WDR37, however, the majority of cases of syndromic PA remains unexplained. [4][5][6][7] Here we report identification of novel variants in CDH2 in four patients with PA.…”

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confidence: 76%

“…The best‐known cause of syndromic PA is classic Peters plus syndrome, characterized by PA, short stature, brachydactyly, dysmorphic facial features, and variable cardiac, genitourinary, and craniofacial defects, and caused by pathogenic variants in B3GLCT . Other occasional genetic causes have been identified, including 8q21 deletions and pathogenic variants in TFAP2A , FLNA , PAX6 , PITX2 , CYP1B1 , FOXC1 , and WDR37 , however, the majority of cases of syndromic PA remains unexplained . Here we report identification of novel variants in CDH2 in four patients with PA.…”

Section: Introductionmentioning

confidence: 99%

Novel variants in CDH2 are associated with a new syndrome including Peters anomaly

et al. 2019

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Peters anomaly (PA) is a congenital corneal opacity associated with corneo‐lenticular attachments. PA can be isolated or part of a syndrome with most cases remaining genetically unsolved. Exome sequencing of a trio with syndromic PA and 145 additional unexplained probands with developmental ocular conditions identified a de novo splicing and three novel missense heterozygous CDH2 variants affecting the extracellular cadherin domains in four individuals with PA. Syndromic anomalies were seen in three individuals and included left‐sided cardiac lesions, dysmorphic facial features, and decreasing height percentiles; brain magnetic resonance imaging identified agenesis of the corpus callosum and hypoplasia of the inferior cerebellar vermis. CDH2 encodes for N‐cadherin, a transmembrane protein that mediates cell‐cell adhesion in multiple tissues. Immunostaining in mouse embryonic eyes confirmed N‐cadherin is present in the lens stalk at the time of separation from the future cornea and in the developing lens and corneal endothelium at later stages, supporting a possible role in PA. Previous studies in animal models have noted the importance of Cdh2/cdh2 in the development of the eye, heart, brain, and skeletal structures, also consistent with the patient features presented here. Examination of CDH2 in additional patients with PA is indicated to confirm this association.

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“…Rare systemic malformations that can be associated with Peters anomaly include spontaneous corneal perforation, Wilms tumor 12 and Goldenhar syndrome identified in our sample population. Differential diagnosis for Peters anomaly includes Cornelia de Lange syndrome, Smith‐Lemli‐Opitz Syndrome, Robinow syndrome, Fetal alcohol syndrome, Rieger syndrome, and Walker‐Warburg syndrome 13 …”

Section: Discussionmentioning

confidence: 99%

Peters anomaly: A 5‐year experience

Salik

Gupta

Tara

et al. 2020

Pediatric Anesthesia

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Background Peters anomaly is a rare, congenital eye malformation characterized by an opaque cornea and blurred vision. Central corneal opacification can lead to delayed progression of visual development caused by defects in Descemet membrane and the posterior stroma. These children require several anesthetics for multiple eye examinations under anesthesia and corneal transplantation. Aims We sought to review the anesthetic management of patients with Peters anomaly for ophthalmologic procedures at Westchester Medical Center, a major referral center for Peters anomaly. Methods A retrospective chart review was completed which included pediatric patients who underwent ophthalmologic procedures related to Peters anomaly from 2013‐2018. Results The charts of 35 patients with Peters anomaly were reviewed: 14 patients with Peters anomaly Type I, 10 patients with Peters anomaly Type II, and 11 patients with Peters plus syndrome. Thirty patients required three procedures on average, two examinations under anesthesia pre‐ and post‐transplant, and anesthesia for the corneal transplant itself. The youngest patient encountered for examination under anesthesia was 39‐week postconceptual age. Anesthetic time for examination under anesthesia averaged 31 minutes using a laryngeal mask airway while corneal transplant averaged 104 minutes utilizing endotracheal intubation. Postanesthesia care unit stay averaged 51 minutes following examination under anesthesia and 65 minutes after corneal transplant. All examinations under anesthesia were successfully completed without adverse events with the use of a laryngeal mask airway. This case series includes two patients with Goldenhar syndrome and Al‐Gazali syndrome accompanying Peters anomaly. Conclusion Although limited by its retrospective nature, this case series describes the cardiac and systemic implications of patients undergoing anesthesia with Peters anomaly. Our experience indicates that general anesthesia and airway manipulation are tolerated with minor postoperative concerns in these infants. Pediatric patients with Peters anomaly require multiple anesthetics for repeated ophthalmologic interventions. The laryngeal mask airway can be routinely utilized in infants less than 3 months of age for an eye examination under anesthesia with no airway complications noted. Perioperative providers should be aware of the multisystemic implications in patients with Peters plus syndrome.

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8q21.11 microdeletion in two patients with syndromic peters anomaly

Cited by 19 publications

References 23 publications

Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype

Chromosomal Microarray Analysis for the Fetuses with Aortic Arch Abnormalities and Normal Karyotype

Novel variants in CDH2 are associated with a new syndrome including Peters anomaly

Peters anomaly: A 5‐year experience

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