Undiagnosed Diseases Network: The Case Of Will Kilquist

There are many genetic disorders that remain unknown to clinicians, which leaves hundreds to thousands living with an undiagnosed illness. But the National Institutes of Health created the Undiagnosed Diseases Network to unravel the mysteries of unknown diseases, including the case of Will Kilquist.

One patient who has been aided by the Undiagnosed Diseases Network is Will Kilquist, a young child, who has been suffering from the inability to sit on his own, unable to swallow without choking, and several intestinal and neurological problems. The UDN program detected the main cause of his disorder.

Scientists Diagnosed Child's Rare Disorder

Will Kilquist, who is turning seven years old, have symptoms that puzzled every clinician who assessed him. The main symptoms detected by the doctors include the patient's lack of ability to sit up, lack of a mechanism to sweat, trouble with swallowing food, and other issues related to the intestines and neurology.

Due to the lack of a solid diagnosis, no specific treatment could be given to Will, which means his disorder would progress without management. So, his parents decided to turn to a new national network founded by NIH that tackles medical cold cases: the Undiagnosed Diseases Network.

The UDN program is composed of scientists with one objective: diagnose medical conditions that did not match any known diseases. Participants who are included in the program do not need to pay in exchange for providing information about mysterious diseases, which can improve the database of diseases and disorders.

In the case of Will, scientists brought him at the NIH Clinical Center in Bethesda. They conducted several tests to determine the main cause of his unusual symptoms. Unlike the previous clinicians, the NIH scientists found something those doctors have missed: the patient cannot produce his own saliva. The inability to secrete saliva has been the primary reason why the patient's throat is usually clogged, which disrupted his ability to swallow properly. This is also the cause why Will does not sweat as a normal person would.

"It kind of put me at peace with myself, knowing there is absolutely nothing I could have done to prevent this, " said Karl Kilquist, father of Will who resides in Illinois with Will's mother and siblings, quoted Daily Mail.

The discovery of the primary cause of Will's condition enabled the scientists to provide specific treatments. Right now, the patient uses a wheelchair to sit him correctly and a feeding tube so he can eat without choking. He is also receiving a therapy provided by the scientists.

The scientists have found a gene defect in the patient that interferes with the proper transport of essential nutrients to cells, which triggered Will's developmental issues. However, the name of the disease has not been disclosed yet.

Benefits of Genetic Diagnosis

Even with the advancement in medicine, thousands of patients around the world remain undiagnosed of their illnesses, and most of them are afflicted with genetic disorders – one of the most difficult to treat conditions. The aim of UDN is to unlock these genetic disorders, provide an accurate diagnosis for patients, and establish a pathway to develop therapies.

In 2014, the UDN was formed as a network of seven clinical sites, two sequencing cores, and one coordinating center. During this time, the scientists accepted potential patients who bear an unknown genetic disorder.

About 1, 519 patients, 53 percent of them were female, have been referred to the program and 601 of them were accepted for medical evaluation. Among those who have been accepted for evaluation, 192 patients were found to have undergone an exome sequencing, a type of genetic sequencing test. Symptoms identified from those patients include neurological problems, musculoskeletal issues, immunological abnormalities, gastrointestinal irregularities, and rheumatological anomalies.

Among 382 patients who have completed the medical evaluation, about 132 of them received a medical diagnosis. Out of those diagnoses, 11 percent was accomplishment through clinical review only while 74 percent was confirmed via an exome or a genome sequencing. About 21 percent of those diagnoses resulted in changes of treatments, 37 percent led to alterations in proper diagnostic testing, and 36 percent drove variant-specific genetic counseling.

This study, which covered patients from September 16, 2015, to May 23, 2017, resulted in a total of 31 newly diagnosed disorders, including genetic conditions. The 132 diagnoses accomplished from 382 patients, who completed the evaluation, reflected the diagnosis rate of 35 percent of the UDN program.

"In summary, the UDN represents an effort to help patients who remain without a diagnosis despite, in most cases, years of medical attention. An important issue is the extent to which this model or lessons from this network can be applied to the broader health care system," scientists wrote in their paper.