Serving the Undiagnosed

Obtaining an accurate diagnosis is key to getting appropriate medical treatment. Many patients with rare disorders confront chronic illness, going from doctor to doctor, with no clear answers. Advances in diagnostic technology, including the ability to sequence genomes, has opened the door to matching patients with known rare diseases as well as discovering new ones. Bringing such technologies to patients is a focus of various rare disease organizations and advocacy groups, including the Rare Genomics Institute. The U.S. National Institutes of Health has joined the effort in recent years with the establishment of the Undiagnosed Diseases Network (UDN). The UDN consists of more than a dozen medical and research institutions located throughout the U.S. that seek to find diagnoses for patients who have unidentified chronic conditions. Patients apply to the main UDN website https://undiagnosed.hms.harvard.edu/apply/ and can be matched to a center nearest their home.

One UDN site is the Stanford Center for Undiagnosed Diseases in Palo Alto, California. Patients who have an objectively defined abnormal condition that has come up negative through extensive conventional testing can access the service by applying online. They will fill out a brief application, including demographic information and details about their undiagnosed condition, and attach a recommendation letter from their physician. Once an application is received, a research coordinator will follow-up to obtain relevant medical records. The application is reviewed by the site’s clinical team and a decision is made on acceptance. 

Obtaining a Rare Diagnosis

For Danny and Nikki Miller, the search for answers on a mysterious illness that afflicted their two boys, Carson and Chase, was daunting. Initially, there were no indications that anything was amiss. After 7-8 months, Carson’s movements and developmental milestones weren’t matching up with other kids his age. His movements seemed stiff, he wasn’t crawling, he didn’t vocalize much and his hands fisted quite a bit. Cerebral palsy was suspected. Later, after a second child Chase was born, the same pattern of developmental delays reappeared. At this point, Danny and Nikki became very worried. They spent the next two years seeing different specialists with their two boys and getting no answers. Genetic screening, including panel testing, karyotyping and whole exome sequencing was performed with inconclusive results.

In 2017, the Marin County, California family turned to the Stanford branch of the NIH Undiagnosed Diseases Network for help. There were visits with a geneticist, neurologists, a neuro-opthamologist, and blood and skin samples were taken. Whole genome sequencing of all four family members was performed and the mystery began to unravel. A diagnosis of an ultra-rare neurodegenerative mitochondrial disease, MEPAN Syndrome, was established in early 2018. The syndrome is so rare that only 13 patients are known worldwide.