Description

Angelman syndrome (AS) is a neurogenic genetic disorder characterized by developmental delay, intellectual disability, lack of speech, seizures and walking and balance disorders. Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypogonadism, hypotonia (weak muscle tone), intellectual disability, short stature and an uncontrolled appetite that leads to life-threatening obesity.

The diagnosis of AS or PWS can be established through a variety of biochemical and genetic tests including deoxyribonucleic acid (DNA) methylation analysis, chromosomal microarray (CMA) (also referred to as comparative genomic hybridization [CGH]), sequence analysis, deletion/duplication analysis, fluorescent in situ hybridization (FISH), uniparental disomy (UPD) and imprinting defect (ID) studies.

For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy:

• DNA banking or preservation
• General population screening
• Individual 17 years of age or younger for adult-onset conditions
• Interpretation and reporting for molecular pathology procedure
• Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)
• Repeat germline or somatic genetic testing
• Retrieved archival tissue

Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available.

Coverage Determination

Any state mandates for genetic testing take precedence over this medical coverage policy.

Genetic testing may be excluded by certificate. Please consult the member's individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding General Criteria for Genetic and Pharmacogenomics Tests, please refer to Genetic Testing Medical Coverage Policy.

Angelman Syndrome

Humana members may be eligible under the Plan for genetic testing to confirm a diagnosis of AS when the following criteria are met:

1. Pre- and post-test genetic counseling; AND

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Presence of developmental delay or intellectual disability as defined by the presence of impaired intellectual and adaptive functioning in at least 1 adaptive domain; AND
• Presence of gait ataxia and/or tremulous movement of the limbs; AND
• Presence of severe speech impairment; AND
• Presence of unique behavior with inappropriate happy demeanor that includes frequent laughing, smiling and excitability

AS Testing Strategy:

Testing begins with DNA methylation analysis of the 15q11.2 – q13 chromosome region (e.g., UBE3A gene):

1. If DNA methylation analysis is normal and suspicion for AS remains, then proceed to UBE3A sequence analysis, OR
2. If DNA methylation analysis is pathogenic or a likely pathogenic variant is identified, then proceed to CMA/CGH gene-targeted analysis
3. If CMA/CGH analysis is normal, then proceed to UPD study
4. If UPD is normal, then proceed to ID study

Prader-Willi Syndrome

Humana members may be eligible under the Plan for genetic testing to confirm a diagnosis of PWS when the following criteria are met:

• Pre- and post-test genetic counseling; AND

Individual is between birth through 1 year of age with the following characteristics:

• Hypotonia with poor suck; OR

Individual is between 2 through 5 years of age with the following characteristics:

• Global developmental delays (GDD) as defined by the presence of delay in at least 2 developmental domains*; AND
• Hypotonia with history of poor suck; OR

Individual is between 6 through 12 years of age with the following characteristics:

• Excessive eating with central obesity if uncontrolled; AND
• GDD as defined by the presence of delay in at least 2 developmental domains*; AND
• History or presence of hypotonia with poor suck; OR

Individual is 13 years of age or older with the following characteristics:

• Excessive eating with central obesity if uncontrolled; AND
• Hypothalamic hypogonadism; AND
• Intellectual disability as defined by the presence of impaired intellectual and adaptive functioning in at least 1 adaptive domain*

*Developmental domains are gross/fine motor, speech/language, cognition, social/personal and activities of daily living

PWS Testing Strategy:

Testing begins with DNA methylation analysis of the 15q11.2 – q13 chromosome region (e.g., SNRPN gene)

1. If DNA methylation analysis is pathogenic or a likely pathogenic variant is identified, then proceed to FISH or CMA
2. If FISH or CMA is normal, then proceed to UPD study
3. If UPD is normal, then proceed to ID study

Coverage Limitations

Humana members may NOT be eligible under the Plan for genetic testing for AS or PWS for any indications other than those listed above.

This is considered experimental/investigational as it is not identified as widely used and generally accepted for any other proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Additional information about AS and PWS may be found from the following websites:

• Background
• National Library of Medicine Medical Alternatives

Physician consultation is advised to make an informed decision based on an individual's health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.