LETTER OF MEDICAL NECESSITY FOR NOONAN AND/OR LEOPARD SYNDROME GENETIC TESTING
(AMBRY NOONAN REFLEX/CONCURRENT OR LEOPARD SYNDROME TEST)
Date:
Date of service/claim
To:
Utilization Review Department
Insurance Company Name, Address, City, State
Re:
Patient Name, DOB, ID #:
ICD-9 Codes:
This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage
of medically-indicated genetic testing for Noonan and/or LEOPARD syndrome to be performed by
Ambry Genetics Corporation.
Noonan syndrome (NS) is a relatively common autosomal dominant genetic condition that affects 1
in 1,000 to 1 in 2,500 individuals.2,3 Individuals with NS have clinical features that affect multiple
organ systems, including congenital heart defects, developmental delay, and short stature. Some
features of NS can present as early as the prenatal period. Additional clinical features include ocular
abnormalities, reduced fertility due to cryptorchidism in males, renal abnormalities, abnormal
bleeding or bruising, and lymphatic abnormalities. LEOPARD syndrome (Lentigines, ECG
abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of
growth, Deafness) is an autosomal dominant genetic condition with variable expression that has
significant clinical and genetic overlap with NS. Those with these conditions may be much more
common and not recognized through clinical assessment alone, making diagnostic genetic testing
essential in ensuring appropriate care for these individuals.2
Significant aspects of my patient’s personal and/or family medical history that suggest
Noonan syndrome and/or LEOPARD syndrome are below:
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Based on the above, Noonan syndrome and/or LEOPARD syndrome is suspected. The four genes
responsible for the majority of NS and LEOPARD syndrome are: PTPN11 (50% of NS), SOS1 (1013% of NS), RAF1 (3-17% of NS), and KRAS (<5% of NS).3 PTPN11 and RAF1 mutations are seen in
about 93% of individuals with LEOPARD syndrome. Due to the clinical overlap and reasonable
probability of detecting a mutation in my patient, this multi-gene test is the most efficient, costeffective way to analyze the genes associated with Noonan syndrome and/or LEOPARD syndrome.
Identifying a causative mutation in one of these genes using molecular genetic testing will
directly impact my patient’s care and management. A positive test result would ensure my
patient is getting appropriate management which can include: cardiac evaluation, coagulation
screening, hearing evaluation, and renal evaluation. These would be warranted to initiate treatment
before symptoms become severe. A positive test result would also help clarify/inform reproductive
decision making for at-risk family members (including prenatal genetic testing).1
Due to the interventions available to reduce morbidity associated with characteristics of Noonan
syndrome and/or LEOPARD syndrome, this genetic testing is medically indicated. As such, I am
ordering this testing as medically necessary and affirm that my patient has provided
informed consent for genetic testing.
A positive test result would confirm a genetic diagnosis in my patient, and would ensure my patient
is being managed appropriately. I am specifying Ambry Genetics Corporation because this
laboratory has highly sensitive and cost-effective testing for Noonan Syndrome and/or LEOPARD
syndrome, along with a large database of tested patients to ensure highly validated, accurate, and
informative test interpretation.
I recommend that you support this request for coverage of diagnostic genetic testing for Noonan
syndrome and/or LEOPARD syndrome in my patient. Genetic testing can take up to several weeks
to complete and the laboratory will not bill until testing is concluded. Therefore, we are requesting
that the authorization be valid for 3 months.
Thank you for your time and please don’t hesitate to contact me with any questions.
Sincerely,
Ordering Clinician Name (Signature Provided on Test Requisition Form)
(MD/DO, Clinical Nurse Specialist, Nurse-Midwives, Nurse Practitioner, Physician Assistant, Genetic
Counselor*)
*Authorized clinician requirements vary by state
Test Details
CPT codes:
81406x3, 81405x1
Laboratory:
Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAPaccredited and CLIA-certified laboratory located at 15 Argonaut, Aliso Viejo, CA
92656
References:
1. Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis,
and management guidelines. Pediatrics. 2010;126:746–59.
2. Bhambhani V, Muenke M. Noonan syndrome. Am Fam Physician. 2014 Jan 1;89(1):37-43.
3. Allanson JE and Roberts AE. Noonan Syndrome. GeneReviews. Pagon RA, Adam MP,
Ardinger HH, et al. , editors. Seattle (WA): University of Washington, Seattle; 1993-2015.