FXTAS Testing & Diagnosis

Robert& Annabelle FXTASFXTAS only occurs in individuals who have a Fragile X (FMR1) premutation. Therefore, it is essential that anyone being considered for this diagnosis is tested for and confirmed as a premutation carrier. This involves DNA testing of the individual’s FMR1 (Fragile X) gene.

Diagnosing FXTAS

The symptoms of FXTAS are divided into “minor” and “major” clinical and MRI findings. The diagnosis is then categorized into “definite,” “probable” or “possible” FXTAS. The criteria were developed primarily as a reflection of the presenting symptoms in men. As we learn more about FXTAS in females, the diagnostic criteria may become different for females, since they usually have milder symptoms.

Also, there are symptoms of FXTAS that are considered “co-morbid,” which means they often occur in individuals with FXTAS but aren’t used to confirm the diagnosis (just as a sore throat is a symptom of strep throat, but cultures, fever, etc. are also used to make the diagnosis).

Major FXTAS Symptoms

  1. Intention tremor: A tremor of the hand when using utensils, writing instruments, reaching for or pouring something. The tremor is not as apparent at rest.
  2. Gait ataxias: Balance problems which may include falling, needed support when walking or going up/down stairs, trouble stepping on/off curbs, generalized instability, or display of a “wide-based” gait.
  3. MRI findings strongly associated with (but not unique to) FXTAS. These findings include “white matter lesions involving middle cerebellar peduncles”, or “MCP” signs.
  4. Neuropathology findings called “FXTAS inclusions” within brain cells.

Minor FXTAS Symptoms

  1. Parkinsonism (resting tremors).
  2. Short -term memory problems. This can be difficult to determine since it is natural for short-term memory to deteriorate as we age. However, in FXTAS it can change more rapidly than normal or may be more dramatic, such as forgetting what one ate, said or did shortly after the event.
  3. Problems with “executive function” and decision-making. Executive function includes the ability to initiate and complete an activity, to adapt and change behavior as needed, and to anticipate and plan for new tasks and situations. Executive function allow us to anticipate outcomes, solve problems, and generalize from one situation to the next.
  4. MRI findings that are more general than those listed above, referred to as “lesions of cerebral white matter.”
  5. MRI findings indicating “moderate to severe generalized brain atrophy.”

Other FXTAS Symptoms (not considered “official” diagnostic criteria)

  1. Neuropathy or numbness/tingling of the extremities.
  2. Mood instability, irritability, explosive outbursts, personality changes.
  3. Cognitive decline—loss of skills including math, reading, etc.
  4. Impotence, loss of bladder or bowel functions (called “autonomic functioning” problems).
  5. High blood pressure, thyroid disorders, fibromyalgia (more common in females and very common in the general population).

Definite vs. Probable vs. Possible FXTAS

Definite FXTAS

  • Individuals with one “major” clinical symptom (#1 or 2 under “major” symptoms) and one “major” radiological symptom (#3 or 4 under “major” symptoms).
  • Any individual with the presence of FXTAS inclusions based on neuropathology.

Probable FXTAS

  • Individuals with two major clinical symptoms (both #1 and 2 under “major” symptoms).
  • Individuals with one “minor” clinical symptom (#1, 2 or 3 under “minor symptoms) and one major radiological symptom (# 3 or 4 under “major” symptoms).

Possible FXTAS

  • Individuals with one major clinical symptom (#1 or 2 under “major” symptoms) and one minor radiological symptom (#4 or 5 under “minor” symptoms).

Any individual who may be a Fragile X carrier (with or without a family history of Fragile X) or who has symptoms in any of these three categories should be seen by a neurologist, movement disorders specialist or psychiatrist familiar with FXTAS or the other Fragile X conditions.