81241

FMR1 (fragile X mental retardation 1) gene analysis; evaluation to detect abnormal (e.g., expanded) alleles

CPT code 81241 describes a molecular diagnostic test that specifically analyzes the FMR1 gene to detect abnormal (e.g., expanded) trinucleotide (CGG) repeat alleles. This analysis is crucial for diagnosing Fragile X syndrome, which is caused by a full mutation (greater than 200 CGG repeats) in the FMR1 gene. It also identifies premutation alleles (55-200 CGG repeats) associated with Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI), as well as intermediate or 'gray zone' alleles (45-54 CGG repeats) and normal alleles (less than 45 CGG repeats). The test typically employs methods such as PCR amplification combined with fragment analysis or Southern blot analysis to accurately determine the number of CGG repeats.

Clinical Indications

  • Diagnosis of Fragile X syndrome in individuals with intellectual disability, developmental delay, autism spectrum disorder, or characteristic physical features.
  • Genetic counseling and carrier screening for individuals with a family history of Fragile X syndrome, unexplained intellectual disability, or autism.
  • Evaluation of women with primary ovarian insufficiency (POI) or premature menopause.
  • Evaluation of individuals presenting with late-onset tremor, ataxia, or parkinsonism suspected of having FXTAS.
  • Prenatal diagnosis or carrier status determination in at-risk pregnancies, typically following identification of a carrier parent or a family history of Fragile X.
  • Differential diagnosis for conditions mimicking Fragile X syndrome.

Procedure Steps

  1. Obtain a biological sample (e.g., peripheral blood, buccal swab, amniotic fluid, chorionic villus sample) from the patient.
  2. Extract genomic DNA from the collected sample.
  3. Perform polymerase chain reaction (PCR) amplification specific to the CGG repeat region of the FMR1 gene.
  4. Analyze the amplified DNA fragments using techniques such as capillary electrophoresis (fragment analysis) or Southern blot to determine the number of CGG repeats.
  5. Interpret the results to classify the FMR1 allele size as normal, intermediate (gray zone), premutation, or full mutation.
  6. Generate a comprehensive laboratory report detailing the findings and their clinical significance.

Coding Guidelines

  • CPT code 81241 should be reported once per patient per encounter for the FMR1 gene repeat expansion analysis, regardless of the number of methods used (e.g., PCR, Southern blot) to achieve the result.
  • This code specifically covers the evaluation to detect abnormal (expanded) alleles and should not be billed in conjunction with other FMR1 gene analyses (e.g., sequence analysis) unless distinct and separate tests are performed for different clinical indications (e.g., if a deletion/duplication or point mutation analysis is separately indicated and performed).
  • Medical necessity must be clearly documented in the patient's medical record, including the clinical indication for testing (e.g., family history, symptoms, carrier screening request).
  • Providers should consult specific payor policies regarding coverage for genetic testing, carrier screening, and prenatal diagnosis for Fragile X syndrome, as coverage criteria may vary.
  • This code does not include genetic counseling services, which should be billed separately if performed (e.g., CPT codes 96040).

Associated ICD-10 Codes