What is the definition and significance of fetal hypoplastic nasal bone?

Fetal Hypoplastic Nasal Bone: Definition and Clinical Significance

Definition

A hypoplastic nasal bone in the second trimester is defined by multiple measurement criteria: a biparietal diameter-to-nasal bone ratio ≥10 or 11, absolute length <2.5 mm, gestational age-based percentiles <2.5th percentile, or multiples of the median <0.75 or 0.7 MoM, with the latter demonstrating superior test characteristics for trisomy 21 detection. 1

The nasal bone must be imaged perpendicular to the longitudinal axis of the nose in the midsagittal plane of the fetal face for accurate assessment. 1

Clinical Significance

Prevalence and Ethnic Considerations

• Absent or hypoplastic nasal bone occurs in 0.1% to 1.2% of euploid (chromosomally normal) pregnancies. 1
• Significant ethnic variation exists, with up to 9% prevalence in Afro-Caribbean populations, though no difference has been demonstrated between White and Asian populations. 1
• This ethnic variability is a critical pitfall when interpreting this finding, as false-positive rates vary substantially by population. 1

Association with Aneuploidy

The association between absent or hypoplastic nasal bone and trisomy 21 (Down syndrome) is well-established, with a positive likelihood ratio of 23 when combined with other markers, but only 6.6 when isolated. 1

• The prevalence of Down syndrome in fetuses with absent or hypoplastic nasal bone is 8.5% compared to 0.42% in fetuses with normal nasal bone (statistically significant difference). 2
• Beyond trisomy 21, hypoplastic nasal bone can indicate trisomy 18, trisomy 13, and other genetic syndromes. 3
• When hypoplastic nasal bone is non-isolated (accompanied by structural anomalies), chromosomal aberrations are found in 57% of cases versus only 7.1% in isolated cases. 3
• Pathogenic copy number variants are detected in approximately 10% of cases with hypoplastic nasal bone, and this finding may serve as an objective marker of facial dysmorphism associated with clinically relevant genetic abnormalities. 4

Management Algorithm Based on Prior Screening Status

No Previous Aneuploidy Screening

For patients with isolated absent or hypoplastic nasal bone and no prior screening, counsel regarding trisomy 21 probability and offer noninvasive aneuploidy screening through cell-free DNA (cfDNA), quad screen if cfDNA is unavailable or cost-prohibitive, or diagnostic testing via amniocentesis based on clinical circumstances and patient preference. 1

Negative Serum Screening Results

For patients with negative serum screening and isolated absent or hypoplastic nasal bone, counsel regarding trisomy 21 probability and discuss options including no further evaluation, noninvasive screening via cfDNA, or diagnostic testing via amniocentesis. 1

• The residual risk may increase above typical thresholds for further evaluation given the high likelihood ratio of this marker and variation in serum screening detection rates. 1

Negative cfDNA Screening Results

For patients with negative cfDNA screening and isolated absent or hypoplastic nasal bone, no further aneuploidy evaluation is recommended, as this finding is most likely a normal variant in the presence of low aneuploidy risk. 1

Additional Considerations

• No additional antenatal ultrasound surveillance is recommended for isolated hypoplastic nasal bone alone. 1
• Careful evaluation of fetal anatomy is warranted, as absent nasal bone can be associated with other genetic syndromes beyond common aneuploidies. 1
• When hypoplastic nasal bone is accompanied by other structural anomalies or soft markers, invasive testing is strongly indicated. 2, 5
• Chromosomal microarray analysis should be chosen over standard karyotype when invasive testing is performed, as it is more sensitive in detecting chromosomal aberrations including pathogenic copy number variants. 2, 3, 4

Critical Pitfalls to Avoid

• Do not recommend invasive testing solely for isolated hypoplastic nasal bone after negative cfDNA screening. 1
• Do not overlook ethnic background when interpreting this finding, as normal variant rates differ substantially. 1
• Do not fail to perform comprehensive anatomic survey, as non-isolated findings dramatically increase aneuploidy risk from 7.1% to 57%. 3
• Do not assume isolated hypoplastic nasal bone in the second trimester requires amniocentesis, as all cases in one study with truly isolated findings had normal karyotype. 5