LETTER OF MEDICAL NECESSITY FOR X-LINKED INTELLECTUAL DISABILITY GENETIC
TESTING (XLID Next-Gen Panel)
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 X-linked intellectual disability genetic testing to be performed by Ambry
Genetics Corporation.
X-linked intellectual disability (XLID) involves a complex collection of clinically and genetically
diverse disorders. The diagnosis of intellectual disability is based on three main criteria: onset of
symptoms before the age of 18, intellectual abilities significantly lower than average, and reduced
adaptive skills. The majority of intellectual disability and/or developmental delay are the result of
an underlying genetic cause, and there are more than 200 identified conditions linked to >100
genes on the X chromosome.2 Pathogenic mutations in these genes can cause intellectual disability,
often accompanied by other congenital anomalies, developmental delay and autistic-like features.1
In addition to intellectual disability, my patient’s personal and/or family history, as relevant
to XLID, is outlined below as applicable:
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This genetic test (XLID Next-Gen Panel) analyzes 81 genes associated with XLID including: ABCD1,
ACSL4/FACL4, AGTR2, AP1S2, ARHGEF6, ARHGEF9, ARX, ATP6AP2, ATP7A, ATRX/XNP/XH2, BCOR,
BRWD3, CASK, CDKL5, CUL4B, DCX, DKC1, DLG3, FANCB, FGD1, FLNA/FLN1, FMR1, FTSJ1, GDI1,
GJB1/CMTX1, GK, GPC3, GRIA3, HCCS, HPRT1, HSD17B10/HADH2, HUWE1, IDS, IL1RAPL1,
KDM5C/JARID1C/SMCX, KIAA2022, L1CAM, LAMP2, MAOA, MECP2, MED12/HOPA, MID1, MTM1, NDP,
NDUFA1, NHS, NLGN3, NLGN4/NLGN4X, OCRL, OFD1, OPHN1, OTC, PAK3, PDHA1, PGK1, PHF6, PHF8,
PLP1, PORCN, PQBP1, PRPS1, RPL10, RPS6KA3/RSK2, SHROOM4/KIAA1202, SLC9A6, SLC16A2/MCT8,
SMC1A/SMC1L1, SMS, SOX3, SRPX2, SYN1, SYP, TIMM8A, TSPAN7/TM4SF2, UBE2A, UPF3B, ZDHHC9,
ZNF41, ZNF81, ZNF674, and ZNF711. Approximately 42% of patients with XLID are anticipated to
have mutations in one of these genes, which each contribute a small portion to the total. As clinical
features of many of these conditions overlap and there is a reasonable probability of detecting a
mutation in my patient, this multi-gene test is the most efficient, cost-effective way to analyze the
multiple genes associated with XLID.
Identifying an underlying genetic etiology for my patient’s symptoms 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:
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Appropriate early intervention management
Guided treatment options depending on the genetic mutation found
Help clarify/inform reproductive decision making for at-risk family members (including
prenatal genetic testing)
This genetic testing (XLID Next-Gen Panel) includes full gene sequencing analysis of 81 genes and
can detect approximately >99% of described mutations in these genes (analytic sensitivity). Due to
the medical risks associated with mutations in these genes 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 XLID, 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 the XLID Next-Gen Panel in my patient.
Depending on the exact test ordered, genetic testing can take up to several months to complete and
the laboratory will not bill until testing is concluded. Therefore, we are requesting that the
authorization be valid for 6 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, 81401x1, 81403x1, 81404x3, 81405x10, 81406x3, 81407x2, 81479x5
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. Gecz J, et al. The genetic landscape of intellectual disability arising from chromosome X.
Trends in Genetics. 2009;25(7):308-316.
2. Tzschach A, et al. Next-generation sequencing in X-linked intellectual disability. Eur J Hum
Genet. 2015 Feb 4. [Epub ahead of print]