Prenatal diagnosis of Wolf–Hirschhorn syndrome: from ultrasound findings, diagnostic technology to genetic counseling

Xing, Yongzhong; Holder, J. Lloyd; Liu, Yong; Yuan, Meizhen; Sun, Qiaoyan; Qu, Xun; Deng, Linbei; Zhou, Jia; Yang, Yazhou; Guo, Mengye; Cheung, Sau-Wai; Sun, Luming

doi:10.1007/s00404-018-4798-1

Cited by 19 publications

(25 citation statements)

References 17 publications

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“…Fetal nasal bone anomaly has been reported to be associated with other rare diseases or syndromes with facial deformities such as Cri du chat (5p-) syndrome, Wolf-Hirschhorn (4p-) syndrome, and Fryns syndrome [1,15,16]. In our study, copy number variation was detected in 9 cases (8.8%), 4 of which were clearly pathogenic, resulting in diseases that also overlapped with the above reports.…”

Section: Discussionsupporting

confidence: 74%

Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

Xie¹,

Wu²,

Su³

et al. 2020

Preprint

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Objective: To explore the significance and value of fetal nasal bone anomaly (absence or hypoplasia) as indications of prenatal diagnosis.Methods: A total of 102 fetuses diagnosed with nasal bone absence or hypoplasia by ultrasonography underwent chorionic, amniotic, or umbilical cord blood puncture. Single nucleotide polymorphism microarray (SNP-array) was used to analyze fetal chromosomes.Results: Of the 102 fetuses with nasal bone absence or hypoplasia, 25 (24.5%) had chromosomal abnormalities, including 15 cases of trisomy 21, one trisomy 18 case, and 9 cases of other copy number variations. Among the 52 cases with isolated nasal bone absence or hypoplasia, 7(13.5%) had chromosomal abnormalities. In 50 cases, abnormal nasal bone with additional soft markers or structural abnormalities was observed, while 18 cases (36.0%) had chromosomal abnormalities, which were significantly higher than that among the fetuses with isolated nasal bone abnormality.Conclusion: Fetal nasal bone absence or hypoplasia can be used as an indication for prenatal diagnosis. The detection rate of chromosomal abnormalities increases with additional soft markers or structural abnormalities. This study demonstrates that fetal nasal bone absence or hypoplasia is associated with micro-deletions or micro-duplications of chromosomes. Application of single nucleotide polymorphism microarray (SNP-array) technology can reduce the rate of missed prenatal diagnoses.

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Section: Discussionsupporting

confidence: 74%

Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

Xie¹,

Wu²,

Su³

et al. 2020

Preprint

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“…A hypoplastic nasal bone is most strongly associated with trisomy 21 but also with other syndromes that can present with facial dysmorphism . There is paucity of evidence as to whether the prevalence of less frequent genetic abnormalities would justify invasive testing in pregnancies with a hypoplastic nasal bone if at low risk for trisomy 21.…”

Section: Discussionmentioning

confidence: 99%

“…An absent nasal bone is also associated with other common aneuploidies such as trisomy 18, trisomy 13, and Turner syndrome . Rare conditions such as Cri du chat (5p‐) syndrome, Wolf‐Hirshhorn syndrome (4p‐), and Fryns Syndrome have also been reported . These conditions are known to have phenotypically unique facial characteristics but can be difficult to detect by ultrasound subjectively, and the nasal bone may offer the means of an objective sonographic marker.…”

Section: Introductionmentioning

confidence: 99%

Hypoplastic nasal bone: A potential marker for facial dysmorphism associated with pathogenic copy number variants on microarray

Nisbet

Reidy

et al. 2019

Prenatal Diagnosis

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Objectives: To compare the frequency of abnormal genetic diagnoses spanning a period before and after the availability of chromosomal microarray analysis (CMA).We hypothesised that microarray would provide additional clinically relevant information in cases of isolated hypoplastic nasal bone.Method: Fetuses with ultrasound-detected hypoplastic nasal bone (absent or <2.5th percentile in length) between 16 and 37 weeks' gestation over a 10-year period were analysed retrospectively.Results: A total of 118 cases of hypoplastic nasal bone met the inclusion criteria. A pathogenic or potentially pathogenic karyotype was detected more frequently in the era where CMA was available (31/60, 52% vs 19/58, 33%). Of these, 25 cases (42%) had common aneuploidies, and six cases (10%) had clinically relevant copy number variants (CNVs). A clinically relevant CNV was detected in two fetuses that presented with isolated hypoplastic nasal bone on initial ultrasound.Conclusion: In addition to its known association with trisomy 21, a hypoplastic nasal bone may be an objective marker of facial dysmorphism associated with clinically relevant CNVs. Our results support consideration of invasive testing with microarray for pregnancies in which a hypoplastic nasal bone has been diagnosed on ultrasound irrespective of a low-risk screening result for common chromosomal abnormalities.

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“…[1][2][3][4][5] Rare conditions have also been reported to be associated with nasal bone absence or hypoplasia, such as Cri du chat (5p-) syndrome, Wolf-Hirschhorn syndrome (4p-), and Fryns Syndrome. [6][7][8] Ultrasound measurement of nasal bone length has become a routine part of prenatal care during the first or second trimester, and is recommended for all pregnant women. However, it is difficult to measure fetal nasal bone length during early pregnancy because of unclear imaging, but image clarity improves as the fetus grows.…”

Section: Introductionmentioning

confidence: 99%

Is Prenatal Diagnosis Necessary for Fetal Isolated Nasal Bone Absence or Hypoplasia?

Zhang¹,

Long²,

Zhou³

et al. 2021

IJGM

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Purpose This study aimed to explore the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal isolated nasal bone absence (INBA) or isolated nasal bone hypoplasia (INBH). We hope to provide additional relevant information for clinical counseling. Patients and Methods From November 1, 2018, to March 1, 2020, 55 pregnant women with isolated nasal bone dysplasia were admitted to the Changzhou Maternity and Child Health Care Hospital. Based on the degree of abnormality, the patients were divided into two groups: INBA and INBH. CMA was performed on all patients. The clinical data and prenatal genetic diagnoses of the two groups were retrospectively analyzed. According to the requirements of WES for samples, 12 cases with negative CMA results were selected for the WES test. Results A total of 55 cases with INBA or INBH met the inclusion criteria. In 35INBA fetuses, there was one case of trisomy 21 and one case of 10q11.22 deletion (5.7Mb), and the abnormality rate was 5.71% (2/35). Compared with INBA fetuses, the abnormality rate was increased in the fetuses with INBH [15.00% (3/20)] (15.00% vs 5.71%); there was one case of 1q21.1 duplication (1.3Mb), one case of Xp22.31 duplication (1.67Mb), and one case of 4p deletion (7.6Mb). In a later retrospective study, two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved RUNX2 and CDH4 genes, respectively. Conclusion A preliminary study confirmed that molecular prenatal diagnosis should be performed in fetuses with INBA or INBH. CMA followed by WES is an effective method.

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Prenatal diagnosis of Wolf–Hirschhorn syndrome: from ultrasound findings, diagnostic technology to genetic counseling

Cited by 19 publications

References 17 publications

Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

Hypoplastic nasal bone: A potential marker for facial dysmorphism associated with pathogenic copy number variants on microarray

Is Prenatal Diagnosis Necessary for Fetal Isolated Nasal Bone Absence or Hypoplasia?

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