Prenatal Workup for Fetal Hypoplastic Nasal Bone
For a fetus with hypoplastic nasal bone, the prenatal workup depends critically on prior aneuploidy screening status: if no prior screening exists, offer cell-free DNA testing or amniocentesis after detailed anatomic ultrasound; if cell-free DNA is already negative, no further aneuploidy evaluation is needed as this is likely a normal variant. 1
Initial Assessment and Measurement Confirmation
Verify accurate measurement technique first: the nasal bone must be imaged perpendicular to the longitudinal axis of the nose in the midsagittal plane of the fetal face to avoid false-positive diagnoses. 1
Confirm hypoplasia using standardized criteria: multiples of the median <0.75 MoM demonstrates superior test characteristics for trisomy 21 detection compared to absolute measurements. 1
Perform detailed anatomic ultrasound to determine if the finding is isolated or associated with other structural abnormalities, as this fundamentally changes risk stratification and management. 1
Risk Stratification Based on Screening History
Scenario 1: No Prior Aneuploidy Screening
Counsel the patient regarding trisomy 21 probability (positive likelihood ratio of 23 when combined with other markers, but only 6.6 when isolated). 1
Offer noninvasive aneuploidy screening through cell-free DNA or diagnostic testing via amniocentesis based on clinical circumstances and patient preference. 1
The isolated finding carries an 8-12% risk of chromosomal abnormalities, while non-isolated findings increase this risk to 24-57%. 2, 3, 4
Scenario 2: Negative Serum Screening Already Performed
Counsel regarding residual trisomy 21 probability despite negative serum screening. 1
Discuss options including no further evaluation, noninvasive screening via cell-free DNA, or diagnostic testing via amniocentesis. 1
The American College of Obstetricians and Gynecologists provides flexibility here, recognizing that serum screening has limitations. 1
Scenario 3: Negative Cell-Free DNA Screening Already Performed
No further aneuploidy evaluation is recommended, as this finding is most likely a normal variant in the presence of low aneuploidy risk. 1
The American College of Obstetricians and Gynecologists explicitly advises against recommending invasive testing solely for isolated hypoplastic nasal bone after negative cell-free DNA screening. 1
Consideration of Chromosomal Microarray Analysis
When invasive testing is pursued (amniocentesis), strongly consider chromosomal microarray analysis (CMA) rather than karyotype alone, as hypoplastic nasal bone may represent an objective marker of facial dysmorphism associated with pathogenic copy number variants beyond common aneuploidies. 5, 2, 3, 4
Recent studies demonstrate that CMA detects clinically relevant copy number variants in 10% of cases with hypoplastic nasal bone, including 2 cases that were initially isolated findings. 5
In non-isolated cases with normal CMA results, monogenic diseases were diagnosed in 44% of cases, suggesting consideration of additional genetic testing when structural abnormalities coexist. 4
CMA identified pathogenic findings in 7-8% of isolated hypoplastic nasal bone cases and 24-57% of non-isolated cases. 3, 4
Critical Ethnic Considerations
Always consider ethnic background when interpreting this finding: hypoplastic nasal bone occurs in 0.5% of Caucasians but up to 9% of Afro-Caribbean populations as a normal variant. 1, 6
The American College of Obstetricians and Gynecologists specifically warns against overlooking ethnic background, as normal variant rates differ substantially. 1
Follow-Up Surveillance
No additional antenatal ultrasound surveillance is recommended for isolated hypoplastic nasal bone alone once aneuploidy risk has been appropriately addressed. 1
This avoids unnecessary anxiety and healthcare costs when genetic testing is reassuring. 1
Common Pitfalls to Avoid
Failing to confirm proper imaging technique leads to false-positive diagnoses and unnecessary interventions. 1
Recommending invasive testing after negative cell-free DNA for isolated findings contradicts current guidelines and exposes patients to unnecessary procedural risk. 1
Using karyotype alone when performing amniocentesis misses clinically significant copy number variants that CMA would detect. 5, 2, 3, 4
Ignoring ethnic background results in overestimation of aneuploidy risk, particularly in Afro-Caribbean populations where this can be a normal variant in nearly 9% of cases. 1, 6