Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

Undiagnosed disorders are often not amenable to the traditional diagnostic approaches and the lack of a diagnosis leads to repeated clinical consultations and laboratory testing, causing substantial personal and familial emotional and financial stress.  For parents of children with undiagnosed diseases, the extensive search for a diagnosis and inherent uncertainty surrounding their child’s health can result in stress, frustration and worries about worsening of symptoms and delays in treatment or inappropriate treatment.  As genetic testing becomes more advanced so do the expectations, associated uncertainty, and if diagnosed, an increased the frequency of a diagnosis of an ultra-rare disorder.  Thus, it is important to describe the complex emotional experience and the relationship to health care engagement and to follow this process in real time with parents as they are experiencing the diagnostic process in order to better understand their needs and to develop strategies to improve outcomes.  Challenges posed by WES for clinicians are largely by virtue of variation in the clinical relevance of results. For instance, many cases require clinical follow-up of variants of uncertain significance and secondary/incidental findings, and it has become necessary communicate effectively with patients/families at multiple stages to both educate and address expectations (pre-test counseling) and relay uncertain or less understood results (post-test counseling). Likewise, parents of children with rare disorders may be challenged to understand the process, the outcome, the certainty of the diagnosis; effectively communicate information to family members and providers; and use the new information to the benefit their of families.  Responsive to these shifting clinical needs, my research is focused on exploring how families manage genetic information with the goal of identifying genetic counseling strategies to facilitate their positive adaptation, coping, and use of information.  

Sujay Kansagra, MD is a professor at Duke and the director the Pediatric Neurology Sleep Medicine Program. He is an active clinician and researcher.  He specializes in treating a variety of sleep disorders, including sleep apnea, insomnia, narcolepsy and parasomnias. His prior clinical research involves sleep pathology in rare conditions such as alternating hemiplegia of childhood and infantile Pompe disease. He has also served as the Duke PI on mult-centered pharmacologic trials involving migraine and narcolepsy.  Dr. Kansagra is the author of numerous peer-reviewed research publications and 5 books. He is currently doing research on novel technology that helps with behavioral insomnia of childhood.

1. Pediatric and adult optic neuropathies
2. Optic nerve imaging (mainly optical coherence tomography)
3. Idiopathic intracranial hypertension
4. Optic neuritis

Role of acid exposure (GERD and dietary acids) on the dentition
Dental Trauma
Etiology of Neonatal Teeth
Caries Risk Assessment

Dr. Joan Mary Jasien completed a med-peds residency and neurodevelopmental neurology and became boarded in internal medicine, pediatrics, neurology and is board eligible for neurodevelopment. She is the co-director of the Multidisciplinary Spina Bifida and Cerebral Palsy Related Conditions Clinics and cares for children and adults with neurodevelopmental disabilities at Duke University Medical Center in Durham, NC, USA. Her research focus is on neurological aging in Spina Bifida and other neurodevelopmental disabilities.