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Rapid Exome-based Testing for Neonatal Crisis

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PreventionGenetics’ Neonatal Crisis panel is a unique ~1,200 gene panel designed for critically ill neonatal and pediatric patients. The panel includes sequencing and copy number variation detection as well as an accelerated turnaround time. The panel has yielded ~17% clear positive results. 

Background

Many known monogenic diseases present early in life as severe neonatal or early childhood (<2 years old) illness. In the United States, such diseases account for ~20% of infant deaths and ~18% of pediatric hospitalizations (Kingsmore. 2012. PubMed ID: 22872815; Saunders et al. 2012. PubMed ID: 23035047). Recent studies have shown that genetic testing in such patients may provide a molecular diagnosis that allows for early intervention for the patient, proper genetic counseling of the family, and shortening of diagnostic odysseys (Ceyhan-Birsoy et al. 2017. PubMed ID: 28079900; Kingsmore. 2012. PubMed ID: 22872815; Meng et al. 2017. PubMed ID: 28973083; Saunders et al. 2012. PubMed ID: 23035047; Stark et al. 2017. PubMed ID: 28125081).

In recent studies, thorough curation of clinically relevant genes has shown that ~500-1000 genes are typically associated with the majority of the severe infant or early childhood onset genetic disorders (Kingsmore. 2012. PubMed ID: 22872815; Ceyhan-Birsoy et al. 2017. PubMed ID: 28079900). For this test, we have included the majority of the genes with definitive or strong evidence to cause a highly penetrant childhood-onset disorder from the most recent study by Ceyhan-Birsoy et al. (2017). In addition, we have included a number of nuclear genes that have been recently associated with mitochondrial disorders (Craven et al. 2017. PubMed ID: 28415858). The ~1,200 genes in the panel have been associated with disorders having severe neonatal or infantile onset. We regularly refine the genes in the panel by adding any additional, newly curated genes and also by removing any that may be unnecessary to include in the panel. The test is indicated for critically ill infants that may present with a wide variety of non-specific symptoms, including but not limited to, respiratory distress, hypotonia, gastrointestinal distress, difficulty feeding, failure to thrive, lethargy, seizures, encephalopathy, cardiac defects, organomegaly, unusual facial features, abnormal odor, and metabolic disturbances (Saudubray and Cazorla. 2016). 

Turnaround Time

Currently, we are reporting sequencing results for 80% of neonatal illness tests at less than 21 days. We continue to reduce this turnaround time as we recognize how critical a rapid report is needed. In some cases, we have reported results in as few as 11 days.

Pricing
Test Type Total Price
Patient Only $2,390
Patient Plus (patient + targeted variant testing of parents. Both parents required) $2,490
Duo (Patient + 1 additional family member) $3,490
Trio (Patient + 2 additional family members) $4,490

Testing should be ordered using the Neonatal Crisis Panel Test Requisition Form. Because this panel is exome-based, clients may reflex to our full PGxome® for $990.

Our Experience

To date, ~17% of cases tested for the Neonatal Crisis Sequencing Panel with Copy Number Variant Detection had a clear positive result (Fig 1). A possible or contributory genetic cause, such as at least one plausible causative variant of uncertain significance in a gene relevant to the patient phenotype, was identified in another ~61% of cases. The remaining ~22% of cases were considered negative. If desired (i.e., when a negative or indeterminate report is issued), clients also have the potential to order a reanalysis of sequencing data to include WES.

Fig. 1, Testing outcomes of neonatal crisis panel at PreventionGenetics