Parents of children with rare diseases may spend years tracking down effective treatments as they manage symptoms—even without a definitive diagnosis. Discerning the cause for your child’s symptoms can help you find better care, which will be crucial for your child’s long-term development.
You have good company on this journey. A burgeoning movement of clinical experts, researchers and advocacy groups has emerged over the past 20 years or so, to ease the path of puzzled parents.
What it means to be “undiagnosed”
What should you do, and where should you go, if after multiple tests, you don’t have an answer, yet your child is still obviously suffering?
Roughly one in 10 Americans, or 30 million individuals, are affected by one or more of 7,000+ rare diseases, according to the National Institutes of Health (NIH), most of which begin to show symptoms in childhood. However, getting a diagnosis takes an average of five to nine years.
Diagnosis can take time because your child might have unusual symptoms of a disorder that doctors don’t recognize, or because a doctor doesn’t have training to associate symptoms with genetic diseases. Complex illnesses may have common symptoms that seem unrelated, because they impact multiple parts of your child’s body, and specialists may struggle to connect the dots. And the basic genetic tests used by many doctors may not be designed to catch every rare disorder.
Christine McGarvey has had an undiagnosed condition all her life. In 2017, McGarvey’s quest took on new urgency after her daughter Brigid, then 3 years old, began suffering similar issues, including constipation and urinary retention – the inability to completely empty her bladder. McGarvey began by gathering her 40 years of medical records from dozens of doctors, which document everything from dysphagia (difficulty swallowing) to peripheral neuropathy (nerve damage in the brain and spinal cord).
To date, McGarvey, who lives in Springfield, PA, is in the dark about the overall cause of her symptoms. “I couldn’t bury my head in the sand. I don’t want my daughter to be treated the way I was treated,” she says. McGarvey mustered new energy on Brigid’s behalf, renewing her efforts to seek an overall diagnosis—now, for both of them.
The costs of diagnosis can extend well beyond the time and expense of doctors’ appointments and tests. McGarvey says she has often had to fight her insurance plans for reimbursements and spent three years pursuing federal disability payments, all of which she believes would have been easier with a diagnosis.
Misdiagnoses can take an emotional toll as well, especially when doctors blame physical symptoms on psychosomatic causes. As a teen, McGarvey was prescribed an anti-depressant for the “social anxiety” believed to be causing her nausea. Many years later, a neurologist dismissed her physical symptoms as the result of post-traumatic stress disorder. Several doctors, stumped, gave her referrals. “I’ve felt like a hot potato,” McGarvey says. “Like ‘I don’t know what’s wrong with you; go see that guy.’”
How to navigate your child’s diagnosis
McGarvey had a rare advantage in seeking a diagnosis for her rare child: She has always loved science, and before being sidetracked by her illness, was on track to get a doctorate in epigenetics. Her confidence with medical systems and jargon helped steer her course.
Fortunately, you don’t need a Ph.D. to get answers—just good information, a lot of persistence, and a smart to-do list.
1. Get informed and connected
McGarvey believes her luck began to change after Brigid’s pediatrician suggested she have her seen at Nemours Children’s Hospital in Philadelphia. There, Brigid was examined by a pediatrician with extensive diagnostic expertise, who suggested that McGarvey apply to enroll her daughter in the Undiagnosed Disease Program at the Children’s Hospital of Philadelphia.
The program is part of the NIH’s Undiagnosed Diseases Program (UDP), which includes the Undiagnosed Diseases Network, a wide network of hospitals and medical schools in 12 U.S. cities, funded by the NIH. The effort’s goals include identifying previously undiagnosed diseases and providing free support to patients with still-elusive disorders. In 2021, the UDP not only accepted Brigid as a patient, but invited her mother to be treated there as well.
The experience has been “transformational,” McGarvey says. “It has been a place of healing in knowing that I’ve done everything possible to help my daughter,” she says. “It has also been a place of peace, knowing that the top physicians and scientists are working on our case. I no longer feel like the captain of my boat trying to keep it upright in the midst of the storm as I navigate uncharted waters… Now I’m more like a passenger.”
Over the past 25 years, the network has diagnosed 697 patients and identified 60 new disorders that have bewildered other clinicians. Thanks to federal funding, the various sites can investigate difficult cases without the normal constraints of doctors with busy practices, says William Gahl, the founder and director of the NIH UDP in Bethesda, MD. “Our consultants are world experts and have time to talk to each other, so we get a multi-disciplinary approach,” he says. Tests can also be offered much faster, as the program doesn’t need to wait for insurance approval.
The UDP is a formidable resource, but spots are scarce and criteria strict. So far, fewer than half of the 6,700 applications have been accepted. You can apply to the network directly online, beginning by providing a detailed medical history, together with a recommendation letter from a healthcare provider, such as a specialist, primary care physician, nurse practitioner, or genetic counselor. (You can also request a paper application.)
Ideal applicants include people without diagnoses despite evaluation by at least two specialists and those who agree to the storage and sharing of information and biomaterials. This is needed so that the symptoms can be studied. Those with self-reported symptoms but no objective findings from doctors, lab tests, or other methods are unlikely to be accepted. After an initial email confirming receipt of materials, it can take up to eight weeks for the network to make a decision.
Aside from the UDP, two other resources for undiagnosed children you should know about include:
2. Assemble your child’s care team
The key to getting a diagnosis is to find specialists who are willing to understand your child, instead of merely offering referrals. Keep looking for medical champions—doctors who genuinely care, even if it means traveling to a teaching hospital or medical center, as McGarvey did.
This applies not only to your child’s primary doctor, but to all specialists. “Medicine is a business, and if you’re not getting the services you’re paying for, you should go with a different provider,” McGarvey says. Over time, her daughter’s care team has grown to include a pediatrician, developmental pediatrician, gastroenterologist, urologist, geneticist, and dermatologist.
3. Take notes
It’s critical to keep careful track of medical records, especially with a multisystem disorder, which is common in rare diseases. “The more detail you have about your child, the better,” says genetics specialist Vandana Shashi, the principal investigator for the UDN at Duke University. “I’m not suggesting you have an Excel sheet. Obviously, parents have enough to do with caring for their children. But do compile medical records and keep note of what tests have been done or not.”
Assembling such objective evidence can be particularly helpful, Shashi adds, when dealing with clinicians who suggest ailments are all in your child’s, or your, head.
To that end, it’s wise to keep a diary of symptoms, and even take videos to illustrate your child’s gait or seizures, if either are a problem, Shashi says. Always alert your medical team if new symptoms emerge or if someone else in your family has been diagnosed with a genetic disease.
4. Pursue genetic tests
Even if your child has already received extensive testing with multiple providers—including genetic tests that came back negative or inconclusive—the cause may still be genetic. Each genetic test is unique to its purpose—as well as to the company that produces it. This means that each test is not always alike. Some tests detect certain genetic mutations, while others do not. It’s important to be as comprehensive as possible. Gahl, who founded the UDP in 2008, credits much of the group’s progress in diagnosing rare diseases to the increased availability of cutting-edge gene-sequencing techniques in recent years. “It’s pretty mind-boggling how well we do now,” he says.
Brigid spent a full day for lab tests and evaluations by different doctors as part of her initial assessment. Subsequently, both she and her mother, for the first time, had genetic testing, looking for potential gene mutations that can run in families. McGarvey later said that she was “shocked” that no doctor had recommended genetic testing previously, given the similar symptoms experienced by mother and daughter.
There are a number of tests used by doctors. If your child has already received genetic testing, it may have been “gene panel sequencing.” Doctors usually start with this basic genetic analysis, which targets well-defined genetic disorders related to a specific symptom, such as an epilepsy panel which targets genes associated with diseases known to include seizures as a symptom.
One of the more advanced genetic testing is called “whole exome sequencing.” UDP patients frequently undergo this testing. This relatively new and cutting-edge technique looks at more complex or undiagnosed cases. It provides a more comprehensive analysis of the protein-coding part of the genome, detecting potential harmful variants in both known and novel genes. Whole exome sequencing also allows for the assessment of “incidental” findings: unrelated genetic variants that may be clinically significant. As with other genetic testing, it’s performed on samples of blood or saliva.
For McGarvey and Brigid, the analysis turned up one intriguing anomaly – a shared genetic variant on the ZBTB40 gene – but still no definitive answer. McGarvey remains hopeful: Given that as many as 80% of rare disorders have a genetic origin, she says perhaps it’s only a matter of time before doctors discover the gene mutation causing their shared symptoms.
5. Get support
Companionship on this often-long journey is essential, says McGarvey, who now volunteers to support other families participating in the UDN. She recommends seeking and regularly communicating with other parents undergoing similar challenges.
With extremely rare diseases, you’re unlikely to find many local families with similar challenges. It’s therefore useful to look online. On social media, try Facebook groups including Parents of Undiagnosed Children and Rare Parenting’s new Parent Support Group. NORD may also have a special Facebook page just for your state.
Allow yourself to feel and express your emotions. “Over the years, I’ve learned to allow myself occasional temper tantrums,” says McGarvey. “If I need to cry, I cry; if I need to scream, I scream. Then with the help of my various supports, I pick myself up and move forward.”
McGarvey says she has also learned to forgive the physicians who haven’t been helpful in the past, adding: “I realized we had a commonality in that we were both afraid of the unknown, and that has helped. But now I have a team of compassionate doctors who are not afraid to navigate these uncharted waters.”
McGarvey’s persistence has paid off for her daughter. The UDP recommended neuropsychological testing, which revealed that Brigid had dyslexia, ADHD, and a learning disability in math and writing. “She now gets more support at school and is on an ADHD medication, which is helping her schoolwork,” says McGarvey. Brigid was also put on two treatments which McGarvey says have helped her and Brigid “tremendously”: a sacral neurostimulator that helps empty the bladder and bowel and a prescription medication for constipation.
Today, McGarvey has reframed the challenges she shares with Brigid. “Being undiagnosed highlights how unique I am! God made me and my daughter this way for a reason, which I believe is to help other rare disease patients and families,” she says.
References and Further Reading