Thousands of babies are born every year with a neurodevelopmental disorder (NDD) that disrupts the development of their central nervous system, and can affect their behavior, memory or ability to learn and move as well as potentially causing epilepsy [1, 2]. Such patients often face many serious health challenges, and 20-30% are misdiagnosed. The diagnostic process can often take up to 7 or 8 years. The tragedy of this diagnostic odyssey is that many children impacted by NDDs do not live more than 5 years, according to RARE Science – a non-profit research organization that focuses on accelerating identification of more immediate therapeutic solutions for children with rare diseases [3].


NDDs can be caused by physical and environmental factors before, during or after birth or through inherited genetic defects. There are more than 1500 genetic loci associated with NDDs, and the mode of inheritance may be recessive, dominant, or X-linked. This can be further complicated by complex inheritance patterns and the effect that the environment may play. This high level of genetic heterogeneity can make achieving a diagnosis in these patients incredibly difficult. A lack of robust phenotypic/ genotypic association can also present a diagnostic challenge to even the most experienced physician or scientist.

Current testing strategies such as chromosomal microarray (CMA)/karyotype, non-genetic analysis, and single gene testing often fail to achieve a diagnosis. A major reason for this is the challenge of resource allocation – we need time, money, and suitably experienced staff for the analysis of NDDs. Gene discovery and understanding of disease mechanisms in the field of NDDs is fast paced. Accordingly, it can be challenging for scientists and physicians to keep pace with current understanding.

Ending the diagnostic odyssey

As mentioned earlier, diagnosis of rare diseases can take up to 7 or 8 years in even the most advanced healthcare systems, with patients often needing input and care from four or five different specialties [3]. Such a lengthy process with no diagnosis at the end, the so called ‘diagnostic odyssey’ is frustrating for patients, parents and healthcare teams – and in severe cases can put the patient’s life at risk.

Experts agree that a whole exome/genome sequencing approach to diagnosis is the best way to end the diagnostic odyssey, as it allows a cost-effective analysis of all known human genes simultaneously [1]. This approach is being pioneered and made possible through national programs such as the 100,000 Genome Project and the UK NHS’ Genomic Medicine Service.

It has also led a coalition of US Senators to introduce the “Ending the Diagnostic Odyssey Act of 2019”, permitting states to use Medicaid funding for whole genome sequencing (WGS) analysis in children with certain rare diseases [4].

Such endeavors require powerful bioinformatic and decision support platforms in order to reduce the cost and time of analysis. In doing so the time to diagnosis is significantly reduced, enabling the healthcare teams caring for these patients to provide more personalized care.

Maximizing efficiency and diagnostic yield

Congenica Neuro is well-placed to help overcome the challenges that arise when considering whole genome or exome analysis in patents with NDDs.

Congenica Neuro takes advantage of all the standard features of the world-leading Congenica decision support platform, while also providing gene curation for specific disease type and a pre-applied, evidenced workflow.

By focusing on de novo variants the analysis is streamlined whilst maintaining an optimized diagnostic yield. Standardized report templates make it easy to communicate clinically actionable outcomes clearly and efficiently. Gene curation was performed using the Genomics England PanelApp resource in conjunction with extensive literature searching. ‘Actionable genes’ (those which are reported in the published literature as having associated therapeutic considerations for epilepsy) were curated, agreed and evidenced in collaboration with scientific and clinical experts in the field.

These features can reduce the time to diagnosis by up to 20X while ensuring diagnostic yield is optimized.

Delivering the human benefit

Congenica Neuro is already being used to help end the diagnostic odyssey for patients and their families. In-depth variant analysis supported clinicians at St. George’s Hospital in South London to diagnose Arvin – a young boy with a complex NDD [5]. In the video below, Arvin’s mother describes the power of a genetic diagnosis and the profound effect it has had on their family, enabling personalized support for Arvin and accurate counselling for family planning. To read about the case in more detail, click here.

Congenica Neuro ® combines expertly curated gene panels and an evidenced workflow to maximize efficiency while helping to improve diagnostic yield. This approach is being used to put an end to the diagnostic odyssey for patients and their families, enabling more personalized care for patients that would otherwise have gone undiagnosed.

Watch our Congenica Neuro webinar to hear Clinical Scientist at Congenica speak on the diagnostic challenges in neurodevelopmental and epileptic disorders.

Watch the full webinar

 

References

  1. How rapid genomic analysis can improve epilepsy diagnosis and treatment https://www.congenica.com/2020/01/28/how-rapid-genomic-analysis-can-improve-epilepsy-diagnosis-and-treatment/
  2. Re-annotation of Developmental and Epileptic Encephalopathy-associated genes unmasks de novo variants https://www.congenica.com/2019/12/05/re-annotation-of-developmental-and-epileptic-encephalopathy-associated-genes-unmasks-de-novo-variants/
  3. https://www.rarescience.org/about-us/
  4. The ending of the diagnostic odyssey https://www.patentdocs.org/2020/01/the-ending-the-diagnostic-odyssey-act-of-2019.html
  5. The power of a genetic diagnosis https://www.congenica.com/2020/03/03/the-power-of-a-genetic-diagnosis/

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