CPT® Code 81331

Official Description

SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (eg, Prader-Willi syndrome and/or Angelman syndrome), methylation analysis

Common Language Description

Methylation analysis is a laboratory procedure that focuses on the examination of specific genetic markers associated with certain genetic disorders, particularly Prader-Willi syndrome and Angelman syndrome. This analysis is crucial for identifying uniparental disomy, which refers to the inheritance of two copies of a chromosome from one parent and none from the other. The SNRPN gene, which encodes for small nuclear ribonucleoprotein polypeptide N, is linked to Prader-Willi syndrome, while the UBE3A gene, responsible for ubiquitin protein ligase E3A, is associated with Angelman syndrome. These genetic mutations typically arise from random events during the formation of reproductive cells, such as eggs and sperm, or during the early stages of embryonic development, rather than being inherited in a traditional manner. Prader-Willi syndrome manifests when there is a deletion of a paternal segment from the SNRPN gene located on chromosome 15, or when there is maternal uniparental disomy, where two copies of the mother's chromosome are expressed. The symptoms of this syndrome can be observed from infancy and may include being small for gestational age at birth, underdeveloped genitalia, feeding difficulties characterized by a weak suck or swallow reflex, failure to thrive, a weak cry, and hypotonia or floppy muscle tone. As the child grows, they may develop skeletal abnormalities, such as small hands, and skin irregularities, including bands, stripes, and lines, along with distinctive facial features. A hallmark of Prader-Willi syndrome is the development of an intense, uncontrollable craving for food during childhood, which can lead to chronic overeating, obesity, respiratory complications, insulin resistance, and right-sided heart failure. On the other hand, Angelman syndrome occurs when the maternal copy of the UBE3A gene is either mutated or lost, preventing its activation in the brain, or when there is paternal uniparental disomy, where two copies of the father's chromosome are expressed. This syndrome is characterized by a complex genetic disorder that affects the central nervous system, leading to developmental delays, speech impairments, ataxia, seizures, and microcephaly. Symptoms typically begin within the first year of life and may progress throughout childhood, presenting as hand flapping, hyperactivity, a short attention span, and sleep disturbances. Genetic testing through methylation analysis is indicated for individuals exhibiting symptoms consistent with either Prader-Willi or Angelman syndromes, providing essential information for diagnosis and management.

1. Indications

The methylation analysis using CPT® Code 81331 is indicated for individuals who exhibit symptoms associated with Prader-Willi syndrome and/or Angelman syndrome. The following conditions warrant this genetic testing:

Prader-Willi Syndrome Symptoms include being small for gestational age at birth, underdeveloped genitalia, feeding difficulties, failure to thrive, weak cry, hypotonia, skeletal abnormalities, and an intense craving for food leading to obesity and related health issues.
Angelman Syndrome Symptoms include developmental delays, speech impairments, ataxia, seizures, microcephaly, hand flapping, hyperactivity, short attention span, and sleep disturbances.

2. Procedure

The procedure for methylation analysis involves several key steps to ensure accurate identification of genetic abnormalities associated with Prader-Willi and Angelman syndromes. The following procedural steps are typically followed:

Step 1: Sample Collection A biological sample, usually blood or saliva, is collected from the patient. This sample contains the DNA necessary for the analysis.
Step 2: DNA Extraction The DNA is extracted from the collected sample using standardized laboratory techniques to ensure purity and integrity for subsequent analysis.
Step 3: Methylation Analysis The extracted DNA undergoes methylation analysis, which involves assessing the methylation patterns of specific regions of the SNRPN and UBE3A genes. This step is crucial for determining whether uniparental disomy or other mutations are present.
Step 4: Data Interpretation The results of the methylation analysis are interpreted by qualified geneticists or laboratory professionals. They will evaluate the methylation status to identify any abnormalities that may indicate Prader-Willi or Angelman syndromes.
Step 5: Reporting A comprehensive report is generated, detailing the findings of the analysis. This report is then provided to the referring physician for further evaluation and management of the patient.

3. Post-Procedure

After the methylation analysis is completed, the patient may not require any specific post-procedure care, as the procedure is non-invasive and does not typically result in complications. However, it is essential for the healthcare provider to discuss the results with the patient and their family. If the analysis indicates the presence of genetic abnormalities associated with Prader-Willi or Angelman syndromes, appropriate counseling and management strategies should be implemented. This may include referrals to specialists, support services, and educational resources to assist in the ongoing care and support of the affected individual.

Short Descr	SNRPN/UBE3A GENE
Medium Descr	SNRPN/UBE3A METHYLATION ANALYSIS
Long Descr	SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (eg, Prader-Willi syndrome and/or Angelman syndrome), methylation analysis
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

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.

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.