Is the Panorama aneuploidy test with 22q11.2 deletion test (81420) medically necessary for a 36-year-old female with a singleton pregnancy?

Medical Necessity of Panorama Aneuploidy Test with 22q11.2 Deletion Screening (CPT 81420)

The Panorama aneuploidy test with 22q11.2 deletion screening is NOT medically necessary for this 36-year-old patient with an uncomplicated singleton pregnancy, as current evidence shows insufficient clinical utility for routine microdeletion screening in low-risk pregnancies, and the insurance policy correctly classifies this as unproven.

Rationale Based on Current Evidence

Standard Aneuploidy Screening vs. Microdeletion Screening

The distinction between standard cfDNA screening for common aneuploidies (trisomies 21,18,13) and expanded microdeletion panels is critical:

• Standard aneuploidy screening for trisomies 21,18, and 13 is well-established and appropriate for this patient's age (36 years) and would be covered under typical prenatal screening guidelines 1
• 22q11.2 microdeletion screening represents an expanded panel that lacks sufficient evidence for routine use in unselected populations, as correctly identified by the insurance policy 2

Evidence Limitations for Routine 22q11.2 Screening

The clinical performance data reveals significant concerns:

• Sensitivity is only 69.6-83.3% for detecting 22q11.2 deletions, meaning approximately 17-30% of affected fetuses would be missed 3, 4
• Positive predictive value in general populations is extremely low at 12.2-52.6%, meaning most positive results are false positives that lead to unnecessary anxiety and invasive testing 3, 4
• Prevalence in unselected populations is only 1 in 1,524, making routine screening inefficient 4

Appropriate Indications for 22q11.2 Testing

Testing for 22q11.2 deletion becomes medically necessary only when specific risk factors are present:

• Fetal conotruncal cardiac anomalies detected on ultrasound (tetralogy of Fallot, interrupted aortic arch type B, truncus arteriosus, ventricular septal defects) - these are present in approximately 65-68% of affected fetuses 1, 2, 5
• Parental 22q11.2 deletion with 50% recurrence risk 1
• Other structural anomalies detected prenatally that raise suspicion, though cardiac anomalies remain the primary indicator 2, 6

This Patient's Clinical Context

Based on the information provided:

• No structural anomalies mentioned - the patient has a "normal first pregnancy" with routine supervision [@case details@]
• Advanced maternal age (36 years) justifies standard aneuploidy screening but does not increase risk for 22q11.2 deletion specifically 1
• No family history of 22q11.2 deletion syndrome reported [@case details@]
• No fetal cardiac abnormalities documented on ultrasound [@case details@]

Approved Testing for This Patient

The following tests ARE medically necessary and should be certified:

• CPT 81161 (DMD duplication/deletion analysis) - approved for carrier screening [@case details@]
• CPT 81220 (CFTR gene common variants) - approved for cystic fibrosis carrier screening [@case details@]
• CPT 81243 (FMR1 gene detection) - approved for fragile X carrier screening [@case details@]
• CPT 81329 (SMN1 gene dosage/deletion analysis) - approved for spinal muscular atrophy carrier screening [@case details@]
• CPT 81408 (molecular pathology procedure level 9) - approved as part of expanded carrier panel [@case details@]

These tests meet criteria for expanded carrier screening in pregnancy planning, as they include cystic fibrosis, spinal muscular atrophy, and will be used in pregnancy management [@case details@].

Clinical Pitfalls to Avoid

• Do not conflate standard cfDNA screening with microdeletion panels - they have vastly different performance characteristics and clinical utility 3, 4
• Recognize that "expanded" or "comprehensive" NIPT panels may include unproven components even when marketed together with validated tests 2
• Understand that low positive predictive values in low-risk populations mean most positive results require invasive confirmation, negating the "noninvasive" benefit 3, 4
• Be aware that negative results do not rule out 22q11.2 deletion given the 17-30% false negative rate 3, 4

Alternative Approach

For this patient, recommend:

1. Standard cfDNA screening for trisomies 21,18, and 13 (without microdeletion panel) given maternal age of 36 years 1
2. Detailed fetal anatomic ultrasound at 18-22 weeks with careful cardiac evaluation, as this remains the primary method for identifying fetuses at risk for 22q11.2 deletion 2, 6
3. If cardiac or other structural anomalies are detected, then diagnostic testing (amniocentesis with chromosomal microarray) becomes appropriate rather than expanded cfDNA screening 2