ExomeDx

The Autism Answers: SHANK3 Inform program is designed for U.S. patients with clinical suspicion of Phelan-McDermid syndrome or SHANK3-related autism spectrum disorder who meet the program's eligibility criteria. A program-specific eligibility and ordering guide is available from GeneDx that details the clinical criteria required. Patients must meet criteria across multiple clinical domains as outlined in the program documentation.

The program utilizes GeneDx ExomeDx whole exome sequencing with deletion/duplication analysis. SHANK3 is analyzed as the gene of primary interest given the indication of suspected Phelan-McDermid syndrome, but because the full exome (approximately 20,000 protein-coding genes) is sequenced, other genetic etiologies for developmental delay or ASD can be identified. Proband-only, duo, and trio configurations are available. If the proband exome is non-diagnostic, genome sequencing can be offered as a next step.

The test is billed to the patient's insurance first. Jaguar Gene Therapy covers the cost of exome testing for patients with Medicare or Medicare Advantage and when commercial insurance coverage is unavailable, so financial barriers are minimized. For claims approved by commercial insurance, the test is processed under the patient's plan as usual; direct any cost-sharing questions to the patient's insurance or your billing team. Ordering through the SHANK3 Inform program carries no purchase or prescribing obligation.

The program requires use of a program-specific test requisition form (TRF) available from GeneDx. The TRF and an eligibility and ordering guide can be downloaded from the GeneDx SHANK3 Inform program page. Ordering through the program carries no purchase or prescribing obligation to Jaguar Gene Therapy or GeneDx.

GeneDx provides genetic counseling support as part of its clinical services. Counselors can assist with pre-test counseling, variant interpretation discussion, and post-test guidance for patients and families. Contact GeneDx directly for details on accessing genetic counseling resources for cases ordered through the SHANK3 Inform program.

No. Ordering whole exome sequencing through the Autism Answers: SHANK3 Inform Partnership Program, sponsored by Jaguar Gene Therapy, carries no purchase or prescribing obligation. The program is designed to support molecular diagnosis of Phelan-McDermid syndrome and related conditions, and the sponsor's coverage of testing costs when insurance is unavailable does not obligate the provider or patient in any way.

Patients may qualify for Autism Answers: SHANK3 Inform Partnership Program if they meet the program's eligibility criteria:

• No prior genetic testing by a clinical laboratory that resulted in a confirmed diagnosis of Phelan-McDermid syndrome (genetically confirmed SHANK3 haploinsufficiency)
• Presents with moderate-to-severe developmental delay, intellectual disability, autism spectrum disorder, or autistic-like behavior, with clinical suspicion of PMS
• Resides in the United States
• Plus, at least 5 features from at least 2 of the following categories:
  • Neurology / neuropsychiatric
    • Psychiatric manifestations or episodes
    • Seizures
    • Regression
    • Sleep disturbances
    • Catatonia
  • Dysmorphic features / musculoskeletal
    • Dysplastic finger- or toenails, long eyelashes, large or fleshy hands
    • Marked hypotonia
  • Language / communication
    • Delayed or absent speech
    • Speech apraxia
  • Motor
    • Delayed motor milestones (rolling over, sitting, crawling, walking)
    • Gross and fine motor impairments
    • Gait abnormalities
  • Sensory / sensory perception
    • Decreased perception of pain (including self-injury)
    • Decreased response to auditory or visual stimuli
    • Decreased perspiration, overheating
    • Pica (and/or mouthing, chewing, or teeth grinding)
  • GI / urinary system dysfunction
    • Bladder or bowel incontinence
    • Gastroesophageal reflux (including difficulty swallowing)
    • Dysmotility (including constipation)