Ordering Recommendation

Preferred test to confirm a suspected diagnosis of neurofibromatosis type 1 (NF1) for individuals not meeting NIH clinical criteria.

Mnemonic
NF1 FGA
Methodology

Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

28-35 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval
Interpretive Data

Background Information for Neurofibromatosis Type 1 (NF1) Sequencing and Deletion/Duplication:
Characteristics:
Neurofibromatosis type 1 (NF1) demonstrates extreme clinical variability. Features include: cafe au lait macules, axillary and inguinal freckling, dermal fibromas, Lisch nodules (iris hamartomas), optic glioma, specific osseous lesions such as tibial pseudarthrosis or sphenoid dysplasia, learning disabilities (50 percent), scoliosis, vertebral dysplasia, and somatic overgrowth. Large NF1 locus deletions increase the risk for neurofibroma development, cognitive abnormalities and malignant peripheral nerve sheath tumors (MPNST).
Incidence:
1 in 3000.
Inheritance:
Autosomal dominant; de novo mutations occur in 50 percent of cases.
Penetrance:
100 percent by adulthood.
Cause
: Pathogenic NF1 mutations.
Clinical Sensitivity:
Approximately 84-93 percent; 77-86 percent of causative mutations are detected by sequencing and 7 percent by deletion testing.
Methodology:
Bidirectional sequencing of the entire NF1 coding region and intron-exon boundaries; multiplex ligation-dependent probe amplification (MLPA) to detect large NF1 locus and intragenic deletions/duplications.
Analytical Sensitivity and Specificity:
99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Large deletions/duplications of exons 11 and 20 will not be detected. The breakpoints of large deletions/duplications will not be determined. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81408; 81479

Components
Component Test Code* Component Chart Name LOINC
2007155 Neurofibromatosis 1 (NF1)Seq,DelDup Spec 31208-2
2007156 Neurofibromatosis 1 (NF1)Seq,DelDup Int 21717-4
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • NF
  • NF1 Sequencing and Deletion/Duplication
  • Von Recklinghausen's Neurofibromatosis (NF1) Sequencing and Deletion/Duplication
Neurofibromatosis Type 1 (NF1) Sequencing and Deletion/Duplication