Chromosomal Microarray Analysis for the Prenatal Diagnosis in Fetuses with Nasal Bone Hypoplasia: A Retrospective Cohort Study

Figures & data

Table 1 Chromosome Karyotyping Detects Abnormal Karyotypes in 21 Fetuses with Nasal Bone Hypoplasia

Fetus No.	Invasive Procedure	Chromosome Karyotype	Ultrasound Findings	Pregnant Outcome
1	AS	Trisomy 21	Fetal nasal bone hypoplasia	Induction of labor
2	AS	Trisomy 21	Fetal nasal bone hypoplasia	Induction of labor
3	AS	Trisomy 21	Fetal nasal bone hypoplasia	Induction of labor
4	CS	Trisomy 21	Fetal nasal bone hypoplasia	Induction of labor
5	AS	Trisomy 21	Fetal nasal bone hypoplasia and nuchal translucency thickening	Induction of labor
6	AS	Trisomy 21	Fetal nasal bone hypoplasia and nuchal translucency thickening	Induction of labor
7	AS	Trisomy 21	Fetal nasal bone hypoplasia and nuchal translucency thickening	Induction of labor
8	AS	Trisomy 21	Fetal nasal bone hypoplasia and nuchal translucency thickening	Induction of labor
9	AS	Trisomy 21	Fetal nasal bone hypoplasia and cysts of the choroid plexus of bilateral ventricles	Induction of labor
10	AS	Trisomy 21	Fetal nasal bone hypoplasia, echogenic bowel and hyperechogenic foci in the left ventricle	Induction of labor
11	AS	Trisomy 21	Fetal nasal bone hypoplasia, echogenic bilateral renal parenchyma, and echogenic hepatic parenchyma	Induction of labor
12	AS	Trisomy 21	Fetal nasal bone hypoplasia, nuchal fold thickening, and aberrant right subclavicular artery	Induction of labor
13	AS	Trisomy 21	Fetal nasal bone hypoplasia, abnormal blood flow signals in the right atrium, suspected right coronary artery-right atrial fistula and hyperechogenic foci in the left ventricle	Induction of labor
14	AS	Trisomy 21	Fetal nasal bone hypoplasia, nuchal translucency thickening, anasarca, endocardial cushion defect and deepening of notched A-wave on venous catheter	Induction of labor
15	CS	47, XYY	Fetal nasal bone hypoplasia	Induction of labor
16	AS	46, XY, del(5) (p15)	Absence of nasal bone	Induction of labor
17	AS	Trisomy 18	Fetal ventricular septal defect, aorta overriding, mild mitral and tricuspid regurgitation, and nasal bone hypoplasia	Induction of labor
18	AS	Trisomy 18	Artialseptal defect, fetal growth restriction, nasal bone hypoplasia and single umbilical artery	Induction of labor
19	AS	Trisomy 18	Fetal growth restriction, ventricular septal defect, high pulmonary artery to aorta ratio, nasal bone hypoplasia and overriding fingers	Induction of labor
20	CS	46, XX, del (4)(p16)	Fetal growth restriction, communicating branch of the portal vein, bilateral small kidney and nasal bone hypoplasia	Induction of labor
21	AS	46, XY, del (4)(p16)	Fetal nasal bone hypoplasia, small left ventricle, aortic stenosis, micrognathia, nuchal fold thickening and single umbilical artery	Induction of labor

Abbreviations: AS, amniocentesis; CS, cordocentesis.

Table 2 Chromosomal Microarray Analysis Detects Copy Number Variations in 10 Fetuses with Nasal Bone Hypoplasia

Fetus No.	Invasive Procedure	Reason for Referral	CMA Detection Results	Clinical Significance	Fragment Size (Mb)	OMIM Gene Number	Known Syndrome	Pregnant Outcome
1	AS	Nasal bone hypoplasia	arr[GRCh37]15q13.2q13.3 (30,386,398_32,444,261)×1	Pathogenic	2.0	7	15q13.3 microdeletion syndrome	Induction of labor
2	AS	Nasal bone hypoplasia	arr[GRCh37]16p12.2 (21,816,542_22,710,614) x1 pat	Pathogenic	0.97	4	Recurrent 16p12.1 microdeletion (neurodevelopmental susceptibility locus)	Induction of labor
3	AS	Nasal bone hypoplasia	arr[GRCh37] 17p12 (14,070,219_15,484,335) x1	Pathogenic	1.4	4	Hereditary Liability to Pressure Palsies (HNPP)	Induction of labor
4	AS	Nasal bone hypoplasia	arr[GRCh37] 15q13.3 (32,021,609_32,444,043) x3 mat	VOUS	0.41	1	15q13.3 microduplication syndrome (neurodevelopmental susceptibility locus)	Normal phenotype after birth
5	AS	Nasal bone hypoplasia	arr[GRCh37]16p13.13p13.12 (11,528,493_12,934,811) x3	VOUS	1.4	9	—	Normal phenotype after birth
6	AS	Nasal bone hypoplasia	arr[GRCh37] 15q11.2 (22,770,421_23,276,833) x1 pat	VOUS	0.50	4	15q11.2 recurrent region (BP1–BP2) (neurodevelopmental susceptibility locus)	Normal phenotype after birth
7	AS	Nasal bone hypoplasia	arr[GRCh37] 2p22.3 (34,002,379_35,076,738) x3	VOUS	1.0	0	—	Normal phenotype after birth
8	AS	Fetal growth restriction, ventricular septal defect, pulmonary valve stenosis complicated by incompetence and nasal bone hypoplasia	arr[GRCh37]15q24.1q24.2 (72,965,465_75,567,135)×1	Pathogenic	2.6	38	15q24 recurrent microdeletion syndrome	Induction of labor
9	AS	Fetal nasal bone hypoplasia, biparietal diameter and humerus length of <2SD, and hyperechogenic foci in the left ventricle	arr[GRCh37] Xq21.33 (95,227,256_95,972,695)×3 pat	VOUS	0.7	0	—	Normal phenotype after birth
10	AS	Fetal nasal bone hypoplasia and ventricular septal defect	arr[GRCh37] 15q26.1 (90,211,822_91,080,606)×1 pat	VOUS	0.85	13	—	Normal phenotype after birth

Abbreviations: AS, amniocentesis; VOUS, variants of uncertain clinical significance.

Table 3 Comparison of Genomic Abnormality Prevalence Between Fetuses with Nasal Bone Hypoplasia Alone and in Combination with Other Ultrasound Abnormalities

Group	Total No. of Fetuses	Total No. of Fetuses with Abnormalities	No. of Chromosomal Abnormality	No. of Fetuses with Abnormal CNVs
Fetuses with nasal bone hypoplasia	32	13	6	7
Fetuses with nasal bone hypoplasia and other ultrasound abnormalities	52	18	15	3
Total	84	31	21	10