Fragile X-associated Tremor Ataxia syndrome (FXTAS)
FXTAS is an adult onset neurological (brain and movement) disorder which affects some Fragile X premutation carriers in later life, involving unsteadiness (ataxia), intention tremor (shaking) and memory problems. FXTAS can often be mis-diagnosed as Parkinson’s disease.
FXTAS was identified in 2001 by Prof’s Randi and Paul Hagerman following observation of a pattern of neurological symptoms present in older grandparents and parents of people with Fragile X syndrome, and subsequent research by their teams.
It is estimated that FXTAS affects approximately 45% of men and 16% of women with the Fragile X premutation who are aged over 40 years. The severity of symptoms increases with advancing age. The type and severity of FXTAS symptoms will vary among individual people. Men with the Fragile X premutation are more often affected than women, and have more pronounced symptoms.(1)
What causes FXTAS?
It is not yet known why some premutation carriers develop FXTAS, and others do not. This is being studied by several research groups internationally, including Dr Danuta Loesch and Prof Elsdon Storey in Australia.
Symptoms of FXTAS
The symptoms of FXTAS are divided into minor and major clinical and MRI findings. Both the type and severity of the symptoms vary between individuals. In women, the symptoms are generally milder.
Major FXTAS Symptoms
- Intention tremor: A tremor of the hand when using utensils, writing, typing, reaching for or pouring something. The tremor is not as apparent at rest.
- Gait ataxia: Balance problems which may include falling, needing support when walking or going up/down stairs, trouble stepping on/off curbs, generalized instability, or display of a wide-based gait.
- MRI findings: The findings are strongly associated with, but not unique to, FXTAS. These include white matter lesions, and frequently involve a middle cerebellar peduncle (MCP) sign.
- Neuropathology findings: These are called “FXTAS inclusions” within brain cells.
Minor FXTAS Symptoms
- Parkinsonism: (resting tremors).
- 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.
- Problems with “executive function” and decision-making: Executive function includes the ability to initiate and complete an activity, to adapt and change behaviour as needed, and to anticipate and plan for new tasks and situations. Executive function allows people to anticipate outcomes, solve problems, and generalize from one situation to the next.
- Additional MRI findings: These are more general than those listed above, and are referred to as “lesions of cerebral white matter.” Other MRI findings include “moderate to severe generalized brain atrophy.”
Other FXTAS Symptoms
These are not considered to be official diagnostic criteria:
- Neuropathy or numbness/tingling of the extremities.
- Mood instability, irritability, explosive outbursts, personality changes.
- Cognitive decline, including loss of skills such as math, reading, etc.
- Autonomic functioning problems such as impotence and loss of bladder or bowel functions.
- High blood pressure, thyroid disorders, fibromyalgia (more common in females and very common in the general population).
Symptoms of FXTAS: Source: National Fragile X Foundation (US) website, at May 2019.
How is FXTAS diagnosed?
A diagnosis of FXTAS is based on symptoms as well as findings from a brain scan (MRI) in premutation carriers, together with a diagnosis of premutation carrier status.
Diagram source: Women’s Health and the Fragile X Premutation, Espinel & Sherman, Emory University, Georgia, USA. 2015
Is there specific treatment for FXTAS?
There is no treatment specific to FXTAS at this time. Each symptom will be treated according to its presentation and severity by medical specialists. A neurologist specialising in movement disorders, together with a GP, may recommend treatment options including medications, physical rehabilitation therapies, and exercise.
This document brings together the views of a number of FXTAS specialists: Treatment guidelines consensus document, National Fragile X Foundation (US)
In Australia two neurology clinics dedicate appointment times to patients who are Fragile X premutation carriers who have been diagnosed with FXTAS or have concerns about developing FXTAS.
St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney, 2010
The FXTAS/FX Premutation Clinic is based within the Movement Disorders Clinic, with clinic places available on the last Monday of each month or otherwise by appointment.
Dr Samuel Bolitho, together with A/Prof Stephen Tisch are Australian neurologists who have been seeing FX premutation carriers and FXTAS patients since 2016.
The establishment of the FXTAS clinic was initiated by the Cunningham family, who are long-term supporters of Fragile X Association of Australia.
To Book an Appointment:
- Contact Fragile X Association of Australia by phone on 1300 394 636 or email to firstname.lastname@example.org OR
- Contact the Movement Disorders clinic at St Vincent’s Hospital direct by phone on 02 8382 3115.
A GP referral to Dr Bolitho or Dr Tisch will be required.
Alfred Health, Caulfield Hospital, 260 Kooyong Road, Caulfield 3162
The clinic is based within the Cerebellar Ataxia Clinic, with clinic places available on two Fridays per month. In addition to assessing and managing people with FXTAS, the clinic has a research focus. The clinic is supported by allied health staff. The clinic is a member of the International FXTAS Consortium of clinics and researchers, an initiative founded by the National Fragile X Foundation (US), MIND Institute UC Davis, and Fragile X Association of Australia.
Dr David Szmulewicz is an Australian neurologist, neuro-ontologist and medical researcher. Dr Szmulewicz undertook cerebellar training with Prof Elsdon Storey and currently collaborates on research into FXTAS with Prof Storey and Dr Danuta Loesch (Latrobe University).
To Book an Appointment:
- Phone 03 9076 6800
A GP referral to Dr Szmulewicz will be required.
Read more: Fragile X Disorders: Don’t Miss Them, R Birch, J Cohen, J Trollor. Australian Family Physician, Royal College of General Practitioners, July 2017.
To Learn more:
There are many sources online which cover FXTAS. This list is not exhaustive.
National Fragile X Foundation (US) website – FXTAS
Treatment guidelines consensus document
National Fragile X Foundation
By Dr Deborah Hall, PhD, neurologist and movement disorder specialist, on National Fragile X Foundation (US) website
Health and wellness for carriers of the Fragile X premutation
Prof Randi Hagerman. 6-minute video produced by Fragile X Association of Australia, September 2018.
Addressing Caregiving needs for a loved one with FXTAS
60-minute webinar recording, from National Fragile X Foundation (US).
Video/webinar by Dr Deborah Hall [ waiting for link ]
Fragile X Association of Australia youtube channel
Several video presentations by Prof Randi Hagerman and Prof Paul Hagerman which cover FXTAS and other Fragile X premutation issues.