LETTER OF MEDICAL NECESSITY FOR RETT/ATYPICAL RETT SYNDROME GENETIC TESTING
Date: Date of service/claim
To:
Re:
Utilization Review Department
Insurance Company Name, Address, City, State
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 Rett/Atypical Rett syndrome, to be performed by Ambry
Genetics Corporation.
Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder that typically affects girls. It represents a common genetic cause of autism spectrum disorders, intellectual disability, and seizures, with an incidence of about 1 in 8,000 females.
1 Girls with RTT typically have uncomplicated pre- and perinatal development followed by developmental stasis – then regression of purposeful hand skills, loss of language abilities, eye pointing, gait dyspraxia, seizures, acquired microcephaly, autonomic nervous system disturbances, and motor deterioration.
2,3 Some have an atypical form of RTT, presenting with intellectual disability with spasticity or tremor, mild learning disability, or an autism spectrum disorder. Atypical RTT shares some features with Angelman syndrome, and those with atypical RTT may initially be misdiagnosed. Males with atypical RTT can present with neonatal encephalopathy and syndromic or non-syndromic intellectual disability.
8
Significant aspects of my patient’s personal and/or family medical history that suggest Rett syndrome/Atypical Rett syndrome are below:
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Based on the above, RTT/Atypical RTT is suspected. The four genes responsible for the majority of
RTT/Atypical RTT are: MECP2 (90% of RTT, 45% of atypical RTT), FOXG1 (~4% of RTT), CDKL5
(13% of atypical RTT), and MEF2C (~2% of atypical RTT).
4,8 Due to the clinical overlap and reasonable probability of detecting a mutation in my patient, this multi-gene testing is the most efficient, cost-effective way to analyze the genes associated with RTT/Atypical RTT.
1,4,5,6,7
Identifying a causative mutation 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 and screening from an early age for maximum benefit. Management options may include: speech, physical/hydro/occupational therapies; braces or splints for orthopedic issues; medications to treat seizures and/or digestive issues; and feeding assistance/nutritional supplementation.
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A positive test result may also help avoid unnecessary testing and/or procedures, and would also help clarify/inform reproductive decision making for at-risk family members (including prenatal genetic testing).
1,9

As a positive result would confirm a diagnosis of RTT/Atypical RTT and would ensure appropriate medical care for my patient, I am ordering this testing as medically necessary and affirm that my patient/patient’s family has provided informed consent for genetic testing. I am specifying
Ambry Genetics Corporation because this laboratory has highly sensitive and cost-effective testing for RTT/Atypical RTT, along with a large database of previously 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
RTT/Atypical RTT 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: 81302x1, 81304x1, 81406x1(Rett Syndrome Concurrent or Reflex)
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.
Giacometti E, et al. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A,
2007;104(6):1931-6.
2.
Laurvick CL, et al. Rett syndrome in Australia: a review of the epidemiology. J Pediatr. 2006 Mar;148(3):347-52.
3.
Hagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev. 2002;8(2):61-
5.
4.
Neul JL, et al. Specific mutations in Methyl-CpG-Binding protein 2 confer different severity in Rett syndrome.
Neurology. 2008 Apr 15;70(16):1313-21.
5.
Archer H, et al. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet. 2006 Sep;43(9):729-34.
6.
Ariani F, et al. FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet. 2008
Jul;83(1):89-93.
7.
Brunetti-Pierri N, et al. Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. Eur J Hum Genet. 2011 Jan;19(1):102-7.
8.
National Institutes of Health. “What are the treatments for Rett syndrome?” From www.nichd.nih.gov/health/topics/rett/conditioninfo/Pages/treatments.aspx
(accessed May 13, 2015)
9.
Nel JL, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50.