LETTER OF MEDICAL NECESSITY FOR FRAGILE X DNA ANALYSIS (FMR1)
Date:
Date of service/claim
To:
Utilization Review Department
Insurance Company Name, Address, City, State
Re:
Patient Name, DOB, ID #
ICD-9 Codes: (list codes)
This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage
of medically-indicated fragile X DNA analysis (FMR1) to be performed by Ambry Genetics
Corporation.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and affects
approximately 1 in 3,600 males and 1 in 4,000 females.1 Individuals with FXS may have cognitive
deficits, dysmorphic facial features, and autism spectrum disorder. FXS is caused by an expansion of
a repeated region of the promoter of the FMR1 gene on the X chromosome. FXS occurs when an
individual has more than 200 copies of the repeated region of this gene, called a full mutation.
FXS is typically inherited from a mother that carries fewer copies of the repeated region of the
FMR1 gene, typically between 55-200 copies; this is called a premutation. While people who have a
premutation do not typically have FXS, they are at risk to have a child with FXS, as the number of
copies of this repeated region can expand to greater than 200 when the gene is passed from parent
to child. It is estimated that 1/350 females and 1/1,000 males in the US carry a premutation.2 Men
and some women that carry a premutation are at risk for fragile X-associated tremor/ataxia
syndrome (FXTAS). Additionally, women with a premutation are themselves at risk for fragile Xassociated premature ovarian insufficiency (FXPOI).
My patient’s personal and/or family history, as relevant to fragile X syndrome, is outlined
below as applicable:



Given the above history, there is a reasonable probability of identifying a premutation or full
mutation in my patient. Per ACMG and ACOG recommendations, fragile X DNA analysis is
warranted.2,3
Identifying the number of copies of the repeated region in the FMR1 gene with molecular
genetic testing will directly impact my patient’s care and management. A positive genetic test
result can provide the following benefits to my patient:



Aid in diagnosis and tailor medical treatment for those with FXS, FXTAS, and FXPOI
Allow my patient to participate in clinical trials for medications or other treatments aimed
at reducing the cognitive and social deficits in those with FXS
Help clarify/inform reproductive decision making for at-risk family members (including
prenatal genetic testing)
This genetic testing (fragile X DNA Analysis) includes FMR1 CGG repeat detection by PCR. If a full
mutation allele is detected, reflex to Southern blot for expansion confirmation and promoter
methylation analysis is performed. Greater than 99% of the FMR1 mutations responsible for FXS
are due to CGG repeat expansions. Due to the medical risks associated with varying repeat sizes in
this gene and available interventions, this genetic testing is medically warranted. 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 and/or risk 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 fragile X DNA analysis,
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 fragile X DNA analysis (FMR1) in my
patient. Depending on the exact test ordered, 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 4 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:
81243x1, 81244x1
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. Seltzer M, et al. Prevalence of CGG expansions of the FMR1 gene in a US population-based
sample. Am J Med Genet B Neuropsychiatr Genet. 2012 Jul;159B(5):589-97.
2. Sherman S, Pletcher BA, Driscoll DA. ACMG Practice Guideline. Fragile X syndrome:
diagnostic and carrier testing. Genet Med. 2005;7(8):584–7.
3. American Congress (formerly College) of Obstetricians and Gynecologists Committee on
Genetics. ACOG Committee Opinion No. 469: Carrier screening for fragile X syndrome.
Obstet Gynecol. 2010 Oct;116(4):1008–10.