CPT® Code 81304

Official Description

MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; duplication/deletion variants

Common Language Description

The CPT® Code 81304 pertains to the molecular genetic testing of the MECP2 gene, specifically focusing on the analysis of duplication and deletion variants. The MECP2 gene is crucial for producing a protein that is essential for normal nerve cell functioning, acting as both a transcriptional repressor and activator within the brain. This protein is predominantly found in neurons, where it plays a vital role in the formation of synapses, which are the connections that facilitate communication between nerve cells. The MECP2 gene is located on the X chromosome and is associated with a paternal-linked autosomal dominant mutation. Mutations in this gene are primarily linked to Rett syndrome, a progressive neurological and developmental disorder that predominantly affects females. In classic cases of Rett syndrome, individuals typically exhibit normal growth and development for the first 6 to 18 months of life, after which they begin to experience significant challenges in language, communication, learning, coordination, and overall brain function. There are atypical forms of the syndrome as well, which may present with varying degrees of severity, including a mild form where speech is preserved and a severe form where there is no period of normal development. Research indicates that approximately 90% of classic Rett syndrome cases arise from new ('de novo') mutations of the MECP2 gene, with no prior family history of the disorder. Although males with the mutation often do not survive past infancy, a small number of males with classic Rett syndrome have been identified, typically possessing an extra X chromosome that allows for the production of sufficient MECP2 protein for survival. The MECP2 gene is subject to various types of mutations, including point mutations, where a single base pair in the DNA sequence is altered, and insertion/deletion mutations that affect the alleles. These mutations have been associated not only with Rett syndrome but also with other conditions such as moderate to severe X-linked mental retardation (XLMR), neonatal encephalopathy, and certain autism cases. The analysis performed under CPT® Code 81304 specifically identifies duplication and deletion variants of the MECP2 gene, which are critical for understanding the genetic underpinnings of these disorders and guiding further testing and family genetic mapping.

1. Indications

The MECP2 gene analysis under CPT® Code 81304 is indicated for the following conditions and scenarios:

Rett Syndrome Identification of MECP2 mutations associated with Rett syndrome, a progressive neurological and developmental disorder primarily affecting females.
Neurological Disorders Assessment of individuals with severe developmental delays, hypotonia, and seizures that may be linked to MECP2 gene mutations.
Familial Testing Genetic mapping for family members of individuals diagnosed with MECP2 mutations to identify potential familial variants.
Other Genetic Conditions Evaluation of MECP2 mutations in individuals presenting with characteristics of both Rett syndrome and Angelman syndrome, as well as in some cases of autism.

2. Procedure

The procedure for CPT® Code 81304 involves several key steps to analyze the MECP2 gene for duplication and deletion variants:

Sample Collection A biological sample, typically blood or saliva, is collected from the patient to obtain DNA for analysis. This sample serves as the basis for the genetic testing.
DNA Extraction The DNA is extracted from the collected sample using standardized laboratory techniques to ensure purity and integrity for subsequent analysis.
Genetic Analysis The extracted DNA undergoes molecular genetic testing specifically designed to identify duplication and deletion variants of the MECP2 gene. This may involve techniques such as quantitative PCR or multiplex ligation-dependent probe amplification (MLPA) to detect the number of gene copies present.
Data Interpretation The results of the genetic analysis are interpreted by qualified geneticists or molecular biologists, who assess the presence of any duplication or deletion variants in the MECP2 gene. This interpretation is crucial for understanding the implications of the findings.
Reporting A comprehensive report is generated, detailing the findings of the MECP2 gene analysis, including any identified variants and their potential clinical significance. This report is then provided to the referring physician for further action.

3. Post-Procedure

After the MECP2 gene analysis is completed, the following post-procedure considerations are important:

Patients and their families may receive genetic counseling based on the results of the analysis. If a duplication or deletion variant is identified, further discussions regarding the implications for the patient and family members will be necessary. This may include considerations for additional testing for relatives, potential clinical management strategies, and understanding the risk of recurrence in future pregnancies. Follow-up appointments may be scheduled to discuss the results in detail and to provide support and resources for affected individuals and their families.

Short Descr	MECP2 GENE DUP/DELET VARIANT
Medium Descr	MECP2 GENE ANALYSIS DUPLICATION/DELETION VARIANT
Long Descr	MECP2 (methyl CpG binding protein 2) (eg, Rett syndrome) gene analysis; duplication/deletion variants
Status Code	Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days	XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC)	9 - Not Applicable
Multiple Procedures (51)	9 - Concept does not apply.
Bilateral Surgery (50)	9 - Concept does not apply.
Physician Supervisions	09 - Concept does not apply.
Assistant Surgeon (80, 82)	9 - Concept does not apply.
Co-Surgeons (62)	9 - Concept does not apply.
Team Surgery (66)	9 - Concept does not apply.
Diagnostic Imaging Family	99 - Concept Does Not Apply
CLIA Waived (QW)	No
APC Status Indicator	Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS)	5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS)	T1H - Lab tests - other (non-Medicare fee schedule)
MUE	1
CCS Clinical Classification	234 - Pathology

59	Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
90	Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GA	Waiver of liability statement issued as required by payer policy, individual case