Making Sense of Multiple Diagnoses

By Brenda Finucane

When it comes to diagnosing Fragile X syndrome (FXS), there is good news and bad news. The good news is that more children than ever are being accurately diagnosed with Fragile X syndrome at an early age. The bad news is that there is a lot of confusion among parents, and even professionals, about the meaning of Fragile X in relation to other types of diagnoses that a child receives.

For example, a 6-year-old girl is diagnosed by a developmental pediatrician as having autism spectrum disorder (ASD) and intellectual disability (ID). At age 8, a blood test shows that she has Fragile X syndrome. Now what? Does she still have those other disorders? Does she now have Fragile X too in addition to intellectual disability and autism?

Similarly, a 10-year-old boy known to have Fragile X syndrome is diagnosed by a child psychiatrist as having ADHD (attention-deficit/hyperactivity disorder ). Does this mean he has now developed a separate, unrelated condition? Understandably, many parents are confused about the “alphabet soup” of diagnoses used to describe their children.

To address these questions, it helps to review the differences between the developmental and genetic diagnostic systems that lie at the heart of this confusion.

Symptoms vs. Causes

First, it’s important to understand the difference between clinical developmental diagnoses, such as intellectual disability and ADHD, and genetic diagnoses, such as Fragile X syndrome. Put simply, developmental diagnoses include disorders with specific patterns of learning and/or behavior that occur during childhood. These are also known as clinical disorders, meaning that they are diagnosed by licensed professionals based on a child’s developmental history and observed symptoms.

The clinical developmental disorders associated with Fragile X syndrome are described in the Diagnostic and Statistical Manual of Mental Disorders↗ (known as DSM-5 because it’s the fifth edition of the book), which is published by the American Psychiatric Association. There are hundreds of different developmental and psychiatric conditions in the DSM-5, including well-known ones such as ADHD, autism, and intellectual disability.

The DSM-5 outlines the behavioral and other criteria that must be met to diagnose a particular developmental or psychiatric disorder.

For example, to meet criteria for a diagnosis of ADHD↗, a child must display certain symptoms of hyperactivity, lack of attention, and impulsiveness. Several of these symptoms must be present by age 12, occur in at least two different settings, and be inconsistent with what is expected for the child’s age. If a child displays behaviors that meet these and other DSM-5 criteria for ADHD, then they may be diagnosed with that disorder.

It’s important to note that clinical developmental and psychiatric diagnoses are not made using blood tests or brain imaging studies, such as MRI, and they generally reveal nothing about the underlying cause of the symptoms. Clinical diagnoses are primarily based on whether or not a person meets the symptom criteria defined in the DSM-5 book, regardless of the cause.

By contrast, Fragile X syndrome is considered an underlying cause (also referred to as etiology) of developmental symptoms. The diagnosis of Fragile X syndrome is based on a highly accurate laboratory test that can detect expansions of the Fragile X gene (FMR1). Large expansions of the gene, known as full mutations, cause FMR1 to shut down, which significantly affects brain function.

By itself, the diagnosis of an FMR1 full mutation does not reveal anything about specific developmental and behavioral symptoms an affected child has or will develop in the future. While FMR1 full mutations cause significant problems with brain function, the symptoms can vary from one person to the next and may fit into one or more different clinical diagnoses.

In fact, virtually all children and adults diagnosed with Fragile X syndrome have symptoms that meet the criteria for at least one (usually more than one) clinical developmental disorder. Intellectual disability, autism, and ADHD are among the most common clinical diagnoses made in children with Fragile X syndrome.

Does this mean that individuals with Fragile X syndrome have several different unrelated disorders? Not at all. They almost always have one underlying cause disorder (Fragile X syndrome) that results in patterns of behavior and learning that meet criteria for multiple symptom disorders (intellectual disability, autism, etc.).

Therefore, the 10-year-old boy with Fragile X syndrome mentioned above who is subsequently diagnosed with ADHD most likely does not have two unrelated conditions: his clinical diagnosis of ADHD is in all likelihood a symptom of his Fragile X syndrome.

So, What Does My Child Have?

Family of four all sitting on their sofaOnce we recognize the difference between symptom and cause diagnoses, it becomes clear that a child or adult may have multiple symptom diagnoses plus a cause diagnosis all at the same time.

Trying to compare these different types of diagnoses is like comparing apples and oranges: they serve different purposes. A Fragile X syndrome diagnosis can answer important questions about the cause of a disability, its genetic implications, associated physical and behavioral symptoms, and potential treatments.

Knowing a Fragile X syndrome diagnosis also allows families to participate in research, including clinical trials, that may one day result in important treatment breakthroughs. Above all, a genetic diagnosis provides the fundamental answer to a parent’s question: What does my child have?

The Importance of Clinical Developmental Diagnoses

Clinical developmental diagnoses are important for other reasons, not the least of which is eligibility for school and therapy services. There are no laws that specifically guarantee an appropriate special education for children with Fragile X syndrome. However, in the U.S. and other countries, laws do exist that give that right to children with certain clinical developmental disorders, such as intellectual disability and autism.

Equally important, clinical diagnoses can guide decisions about psychiatric medications used for the treatment of behavioral symptoms. For example, stimulant medications, such as the drug Adderall, are not specifically prescribed to treat Fragile X syndrome but are often used successfully to treat attention disorders in children with Fragile X syndrome.

Also see: Medications for Individuals with Fragile X Syndrome

The same holds true for non-medical therapies. A child whose autism is due to Fragile X syndrome may still benefit from educational and behavioral interventions developed for children whose autism is not related to Fragile X syndrome.

The bottom line? Understanding the difference between symptoms and causes allows individuals with Fragile X syndrome and their families to access the best of both diagnostic worlds.

*This article was updated in November 2021 by the author, based on a previous version published many years ago by the NFXF.

Brenda Finucane

Brenda Finucane, MS, CGC

Brenda has been actively involved with the Fragile X community for many years and is currently a genetic counseling consultant for the National Fragile X Foundation. She is a long-time member of the Foundation’s Scientific and Clinical Advisory Committee and also served two terms on its Board of Directors. In her day job, Ms. Finucane is a Professor and licensed genetic counselor at Geisinger’s Autism and Developmental Medicine Institute in Lewisburg, PA.

Learn More

Genetic Testing for Fragile X Syndrome and Associated Disorders
There are three general circumstances in which Fragile X testing should be considered, learn more about each and how to work with your physician and genetic counselor.

You and Your Newly Diagnosed Child
This resource is designed to help parents who have a child with a new diagnosis of Fragile X syndrome. We cover self-care, visiting a Fragile X clinic, seeing a genetic counselor, and telling others.

Behavioral Challenges in Fragile X Syndrome
A consensus document from the Fragile X Clinical and Research Consortium, we look at behavior management tools and treatments for the spectrum of behavioral conditions in affected individuals.

Featured image by Arek Socha↗ from Pixabay↗