What is the significance of a frontal bone indentation identified on a routine mid‑trimester fetal anomaly scan, and what further imaging or specialist evaluation is recommended?

Frontal Bone Indentation on Anomaly Scan

A frontal bone indentation identified on mid-trimester anomaly scan requires immediate comprehensive evaluation for skeletal dysplasia, craniosynostosis, and associated structural anomalies, with referral to maternal-fetal medicine and genetics specialists for detailed ultrasound assessment, consideration of fetal MRI, and discussion of genetic testing options.

Clinical Significance and Differential Diagnosis

A frontal bone indentation represents an abnormal skull contour that may indicate:

• Skeletal dysplasia with undermineralized skull – particularly severe forms such as osteogenesis imperfecta type II, achondrogenesis, or hypophosphatasia, which can present with abnormal skull mineralization patterns at the 18-20 week anatomical survey 1, 2
• Craniosynostosis – specifically frontosphenoidal suture synostosis, which develops during the second trimester and causes recession of the lateral frontal bone and supraorbital rim 3
• Isolated ossification defects – rare congenital frontal bone aplasia or ossification defects, though these are uncommon 4

The earlier in gestation that skeletal and structural anomalies are detected, generally the worse the clinical phenotype of the affected fetus 1.

Immediate Evaluation Protocol

Comprehensive Ultrasound Assessment

Perform a detailed anatomical survey to determine if the frontal bone indentation is isolated or part of a constellation of findings 5:

• Skeletal evaluation: Measure all long bones (femur length, humerus length) and compare to gestational age nomograms; look for short limb length (<5th percentile or >2 SD below mean), angular deformities or bowing of long bones, and abnormal chest configuration including bell-shaped thorax or short ribs 1, 2, 6
• Skull assessment: Evaluate for undermineralized skull (appears abnormally lucent), abnormal skull shape, and other cranial bone abnormalities 1
• Facial structures: Assess for flat nasal bridge, absent or hypoplastic nasal bone, micrognathia, and cleft lip/palate 5, 7
• Other soft markers: Look for increased nuchal fold thickness (≥6 mm), echogenic intracardiac focus, echogenic bowel, and shortened long bones 1
• Additional anomalies: Screen for congenital heart disease, renal anomalies, brain abnormalities, and other structural defects 1, 8

Advanced Imaging Considerations

• 3D ultrasound can better characterize skull contour abnormalities, cranial sutures, and skeletal deformities 5, 7
• Fetal MRI should be considered for detailed evaluation of the skull, brain, palate, and other structures when ultrasound findings are suboptimal or additional detail is needed 1, 8, 7
• Avoid plain radiography and CT during pregnancy due to radiation exposure concerns and inability to secure precise fetal positioning 1

Specialist Referral and Genetic Counseling

Immediate referral to maternal-fetal medicine specialist and clinical geneticist with skeletal dysplasia expertise is mandatory 8:

• Consultation should occur in a timely fashion to optimize therapeutic options and provide unbiased counseling respectful of patient choice, culture, religion, and beliefs 8
• Multidisciplinary evaluation allows for accurate diagnosis, prognosis discussion, and informed decision-making 1

Aneuploidy Risk Assessment

If No Prior Aneuploidy Screening

When a frontal bone indentation is accompanied by other skeletal features (shortened/bowed limbs, abnormal chest/ribs, undermineralized skull), this constellation is highly suggestive of severe skeletal dysplasia 1:

• Offer cell-free DNA screening or quad screen if cfDNA is unavailable or cost-prohibitive 1
• Discuss diagnostic amniocentesis based on clinical circumstances and patient preference, particularly if multiple anomalies are present 1
• Counsel on the probability of chromosomal abnormalities, as structural anomalies may be part of a genetic syndrome despite normal karyotype 8

If Prior Screening Was Negative

• No further aneuploidy evaluation is typically needed if isolated finding with negative cfDNA or serum screening 1
• However, structural anomalies may still represent genetic syndromes, sequences, or associations despite normal karyotype 8

Genetic Testing Strategy

Prenatal next-generation skeletal panel gene sequencing or whole exome/genome testing should be offered to increase diagnostic yield when skeletal dysplasia is suspected 1, 2:

• Genomic test results must be ordered and interpreted by a qualified expert (clinical geneticist with skeletal dysplasia expertise) and correlated with clinical findings 1
• Retain fetal DNA for future testing if diagnosis remains unclear 2
• Parental blood testing may be required to clarify diagnosis, particularly for potentially dominant inheritance patterns 8

Serial Monitoring and Follow-up

Repeat ultrasound examinations at intervals depending on the anomaly to assess evolution and detect additional anomalies not previously identified 8:

• This influences counseling and obstetrical/perinatal management 8
• For isolated shortened long bones or skeletal concerns, perform third-trimester ultrasound for reassessment and growth evaluation 1

Delivery Planning and Postnatal Management

If early or urgent postnatal management may be required, delivery at a tertiary center with appropriate neonatal care capabilities should be strongly considered 8:

• Referral to appropriate pediatric subspecialists (pediatric neurosurgery, craniofacial surgery, genetics) should occur prenatally to provide accurate information on prognosis and management 8
• Comprehensive newborn assessment is essential for diagnosis and counseling on etiology, prognosis, and recurrence risk, especially when etiology has not been clearly identified prenatally 8
• Postnatal skeletal radiographic survey should be performed if skeletal dysplasia was suspected prenatally 2

Critical Pitfalls to Avoid

• Do not dismiss as normal variant without thorough evaluation – frontal bone indentation may be the first clue to severe skeletal dysplasia or craniosynostosis 1, 3
• Do not rely solely on 2D ultrasound – utilize 3D ultrasound and fetal MRI when available to better characterize skull and skeletal abnormalities 1, 5, 7
• Do not order genetic testing without expert interpretation – genomic results require filtering and correlation with phenotype by specialists to avoid misdiagnosis 1
• Do not assume normal karyotype excludes genetic syndrome – many structural anomalies represent recognizable syndromes with non-chromosomal genetic basis 8

If Pregnancy Termination or Fetal Demise Occurs

Strongly encourage complete autopsy by perinatal or pediatric pathologist to provide maximum diagnostic information 8:

• If complete autopsy is refused, at minimum obtain partial/external autopsy with X-rays and photographs 8
• This information is crucial for counseling on recurrence risk in future pregnancies 8