Abstract
Fragile X syndrome (FXS) is the first of 3 syndromes identified as a health condition related to fragile X mental retardation (FMR1) gene dysfunction. The other 2 syndromes are fragile X–associated primary ovarian insufficiency syndrome (FXPOI) and fragile X–associated tremor/ataxia syndrome (FXTAS), which together are referred to as fragile X–associated disorders (FXDs). Collectively, this group comprises the 3 faces of fragile X. Even though the 3 conditions share a common genetic defect, each one is a separate health condition that results in a variety of body function impairments such as motor delay, musculoskeletal issues related to low muscle tone, coordination limitations, ataxia, tremor, undefined muscle aches and pains, and, for FXTAS, a late-onset neurodegeneration. Although each FXD condition may benefit from physical therapy intervention, available evidence as to the efficacy of intervention appropriate to FXDs is lacking. This perspective article will discuss the genetic basis of FMR1 gene dysfunction and describe health conditions related to this mutation, which have a range of expressions within a family. Physical therapy concerns and possible assessment and intervention strategies will be introduced. Understanding the intergenerational effect of the FMR1 mutation with potential life-span expression is a key component to identifying and treating the health conditions related to this specific genetic condition.
Fragile X syndrome (FXS), a genetic condition known to be the most common form of inherited intellectual limitation in men, was initially seen as a single disorder associated with mutations in the fragile X mental retardation (FMR1) gene on the X chromosome.1 More recently, however, 2 additional health conditions related to the FMR1 gene were identified: fragile X–associated primary ovarian insufficiency syndrome (FXPOI) and fragile X–associated tremor/ataxia syndrome (FXTAS).2 Together, FXS, FXPOI, and FXTAS represent the 3 faces of fragile X or more specifically of FMR1 gene dysfunction.3 Collectively, the 3 conditions are known as fragile X–associated disorders (FXD).1 These disorders may be misunderstood by the individuals who are affected, their families, and the health care community and are often underdiagnosed. Taken together, these conditions not only have a distinct inheritance characteristic with variable expression over several generations, but they also represent a group of health conditions seen over the life span.
In describing mutations in the FMR1 gene, Saul and Tarleton4 stated that FXS, FXPOI, and FXTAS are the only disorders known to be associated with this specific mutation. Galloway and Nelson5 supported the need to identify carriers of the FMR1 mutation given the high prevalence of this mutation in the general population with the risk, as a carrier, of developing clinical features of FXTAS.
Typically, the patient will be referred for physical therapy to determine how skilled therapy can support addressing goals and minimizing limitations. For the physical therapist, each of these individual diagnoses could present as a series of unique health conditions. The physical therapist may encounter a patient with an undiagnosed FXD at any stage, and, to date, there is a lack of physical therapy literature on the range of clinical presentations that are characteristic of FXD.
Although the 3 components of FXD may be recognized as individual health conditions in practice, understanding of the etiologic relationship of the conditions is limited within the physical therapy community. Also lacking is knowledge of appropriate physical therapy intervention strategies that each condition may require.
The 3 FXD conditions and their genetic basis provide the physical therapist with a clinical example of the need to understand the interaction of genetics and therapy. Curtis, who teaches genetics to third-year DPT students, links genetics to physical therapy.6 She advocates that it is the responsibility of physical therapists to include genomics and genetics as part of what they see and do with patients.6 The American Physical Therapy Association has committed to incorporating genetics into patient management as part of the Guide to Physical Therapist Practice 3.0 (Guide 3.0)7 and, in 2009, passed a policy on genetic literacy for the physical therapist.8
The purpose of this perspective article is to define a 3-fold perspective for physical therapists relevant to FXD. First, the therapist should gain an understanding of the individual genetic picture and pathology of each of 3 FXD conditions. Second, the therapist should be prepared to contribute to the differential diagnosis by defining the specific clinical characteristics that any of the 3 conditions may present in the physical therapy clinic. Third, the therapist should be contributing research on appropriate intervention planning for each of the 3 diagnoses of FXD.
Genetic Characteristics of Fragile X–Associated Disorders
Fragile X syndrome, FXPOI, and FXTAS, grouped as FXD, are 3 distinct clinical entities that share a common genetic basis, specifically changes in the FMR1 gene.1 The genetic basis of FXD is a defective gene characterized by an abnormal expansion of one segment of the DNA chain within the FMR1 gene on chromosome Xq27.3.9 These expansions are called CGG repeats, and the risk for expansions of this mutation remains unclear.9 However, as a consequence of the penetration behavior of the FMR1 gene, this single-gene X-linked disorder creates a set of intergenerational conditions that could be present in both men and women in as many as 4 generations simultaneously.
The CGG repeat refers to a particular order of molecules within the DNA chain. The chain is made up of alternating combinations of 2 of 4 molecules: adenine, thymine, cytosine, and guanine. In the FMR1 gene, cytosine and guanine are paired, and adjacent pairs are labeled CGG repeats.10 The alternate AGG sequence typically occurs after 9 to 10 CGG repeats and is thought to prevent further CGG expansion.9 Repeat lengths of 5 to 44 CGGs in the FMR1 gene have long been recognized as common in the general population and are found at the rate of 1 in 113 to 259 women and 1 in 260 to 810 men.3,11 Above 44 repeats is atypical, and Table 1 summarizes the groupings of CGG repeats in the FMR1 gene.4 Within the category of neurodegenerative disorders, FXS was the first expansion disorder to be described.12 The inheritance picture seen with FXS is part of a group of genetic conditions collectively known as trinucleotide repeat expansion disorders.13 They also are referred to as dynamic mutations.1 The term “trinucleotide repeats” refers to “triplets of nucleotides (ie, CGG, AGG, etc) that occur in the DNA of a gene.”14 In the case of FXS, the repeat is abnormally situated in front of the coding region of the gene, and this disarrangement ultimately leads to gene silencing.9,13
Categories of CGG Repeat Ranges and Effect for Carrier of Premutation of Fragile X
La Spada and Taylor15 published a list of known expansion disorders in 2010, as their group identified trineucleotide repeats as a significant cause of neurodegenerative disorders. Of note is that this initial list included a range of neurodegenerative disorders familiar to physical therapists (eg, Huntington disease, Friedreich ataxia, spinal muscular atrophy).15
With all premutation carriers, CGG repeats above 44 can be found in both men and women. However, expansion to a full mutation (+200 repeats) resulting in FXS occurs only in subsequent generations via maternal transmission through the X chromosome.9,16 In the affected offspring, the consequence of this expansion is an absence of the normally occurring fragile X mental retardation protein.9,17 The primary cause of FXS appears to be a loss of mental retardation protein function, but the actual mechanism of how this occurs at the cellular level has not yet been established.18
Initially, the premutation carrier state was thought to have no clinical significance except for reproductive complications documented for about 20% of women who carry the premutation.3 However, in male premutation carriers, a syndrome with a clinical picture of kinetic tremor, ataxia, and cognitive decline was identified.9 After age ±50 years, these men developed a neurodegenerative ataxia that is now known as FXTAS.9 Without genetic testing for changes in the FMR1 gene, this syndrome can easily be mistaken for Parkinson disease.19 In 2002, the clinical picture of FXTAS also was found to be associated with specific markers in the brain.20,21
Beginning in the early 1990s, female FMR1 gene premutation carriers who had experienced intermittent primary ovarian insufficiency were described. This condition was subsequently named FXPOI22 and is estimated to affect 20% of female premutation carriers.3 Over time, women with FXTAS also were identified, although at a lower rate than their male counterparts.23 It has been reported that 8% of female premutation carriers over the age of 40 years and 20% over the age of 50 years can be expected to develop some symptoms of FXTAS.24,25
Recent evidence suggests that the neurodegenerative nature of FXTAS and most likely FXPOI is the clinical expression of the final degenerative process that is thought to begin in the young child.26 Childhood manifestations include attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs), and manifestations in adults can include depression or anxiety.27
Fragile X–Associated Disorders
Fragile X Syndrome
Typically, the clinical description of FXS includes intellectual disability, but more recently learning disabilities and psychiatric problems were added to more adequately define the full spectrum of the disorder.28 Once known as Martin-Bell syndrome, it was identified as FXS in the 1980s due to the presence of the fragile site at the bottom of the long arm of the X chromosome.1 In 1991, a specific gene for the disorder was discovered and identified as FMR1.28 Most people with FXS may have functional limitations in 3 areas: physical, developmental, and behavioral skills.1,12
The body structure characteristics of an infant or young child with FXS include the presence of mild to moderate low muscle tone, hyperextensible joints, sometimes a long face, usually large ears, scoliosis, and frequently some degree of pectus excavatum.28 If the child can stand, significant pes planus, knee hyperextension, and hip instability may be noted.29 Developmental issues from the therapist's perspective may be intertwined with behavioral traits. Developmental delay also may be related to underlying secondary sensory issues. These underlying secondary sensory issues may be expressed as attention deficits, hyperactivity, tactile defensiveness, perceptual deficits, and learning disabilities.1,4 In this population, visual learning is the best educational format, unless there is a significant problem of ADHD.1,28
In general, the child with FXS will develop at a slower rate than the child who is developing typically and may experience delay in acquiring appropriate functional skills, such as independent walking.4 The older child will be noted to have activity limitations, such as poor balance and coordination.1 Table 2 summarizes primary and secondary physical and behavioral impairments seen in children with FXS.1,28,29
Fragile X Selected Physical and Behavioral Impairments With Potential Impact on the Developing Musculoskeletal System
The FXS and ASD connection is of increasing interest to the medical community. Fragile X syndrome is now accepted as the most common single gene etiology of ASD, and a significant 30% of children with FXS are diagnosed with ASD. Only 2% of children with ASD are confirmed to have the full FMR1 mutation.16(pp186–187) Budimirovic et al30 reported 38% of men and women diagnosed with FXS also are diagnosed with ASD. Furthermore, another 30% are being identified with a primary impairment of ASD (behavioral diagnosis of ASD is outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition31) and a secondary impairment of FXS.32 Although features of FXS overlap with ASD, there are many distinct features specific to FXS. Thus, the dual diagnosis of FXS and ASD may represent a FXS subset.33
Fragile X–Associated Primary Ovarian Insufficiency Syndrome
Women who are premutation carriers of the FMR1 gene were thought to be protected from the detrimental effects of RNA toxicity that is associated with FXTAS in male premutation carriers.9 It is assumed that this protection relates to the fact that women carry an unaffected second X chromosome.9 Initially, only primary ovarian insufficiency was considered a health problem for female premutation carriers of the FMR1 gene. As more female carriers are studied, a more complex picture with a broader range of medical issues and comorbidities is emerging.24
For women who are premutation carriers, there is clear evidence that they, as a group, have a high rate of primary ovarian insufficiency (defined as menopause <40 years of age).24 Currently, women who experience infertility of unknown cause have a 1:50 chance of being a FXPOI premutation carrier of the FMR1 gene.21 Recent evidence suggests that this problem is a late-onset impairment.21 Thus, women in their younger reproductive years may not experience a significant level of FMR1-related reproductive dysfunction but rather potentially a reduced reproductive time line.21 The question of early onset of osteoporosis secondary to premature menopause in people with FXPOI is thought to be a concern but needs to be further researched.34,35
A further problem identified for female premutation carriers is that, similar to male carriers, they may eventually develop FXTAS at an estimated rate of 8% to 16% for women ≥50 years.9,34 The expression of FXTAS appears to be at a lower rate than male carriers experience. Specifically, the clinical picture of neurodegeneration and cognitive decline is typically less significant in women.34 For this group of women who are usually aged ≥50 years, the list of neurological findings can include symptoms such as numbness, tingling in extremities, neuropathy, muscle pain, and autonomic dysfunction (eg, hypotension, frequent fainting, dizziness) that do not meet the criteria of FXTAS.34 Current thinking is that these symptoms are related to the RNA toxicity, as seen in premutation carriers, and are less likely the result of stress associated with the diagnosis.3 A small study of 8 FXTAS/FXPOI cases points to a stronger-than-expected association between FXTAS and Alzheimer disease. This preliminary finding supports 2 concepts. First, dementia in female carriers appears to be more common than had previously been recognized. Second, the actual clinical expression is characteristically different than other dementias in that high rates of sleep problems, anxiety, and depression are noted.36,37
Finally, we should recognize that current research related to female premutation carriers is primarily based on populations of “reverse-associated” individuals. That is, the parent was labeled as a premutation carrier only after her offspring was diagnosed with a full FMR1 mutation.3
Fragile X–Associated Tremor/Ataxia Syndrome
Before 2001, it was thought that male premutation carriers of the FMR1 gene would pass the gene on to their daughters, but themselves experience no consequences to their health.9 In early 2001, Hagerman et al38 reported on grandfathers of children with FXS who appeared to be showing a high rate of symptoms, including gait deterioration, tremor, and ataxia. In many cases, these same men frequently had a diagnosis of Parkinson disease, essential tremor disorder, Alzheimer disease, dementia, or ataxia of unknown etiology.38,39 It is now clear that Hagerman et al had identified a specific neurodegenerative disorder (ie, FXTAS) that is directly related to the premutation state of the men.18,21
For the clinician, identifying diagnostic overlap with other neurodegenerative disorders is an important consideration when treating a person with FXTAS. The clinical picture of FXTAS is highly variable and complex. This complexity is related to underlying cytological reasons.9 Fragile X–associated tremor/ataxia syndrome with an FMR1 premutation is a separate neurodegenerative disorder from Parkinson disease and multiple systems atrophy, neither of which have the FMR1 gene basis.9 Details of diagnostic differences are illustrated by the comparison chart shown in the eAppendix. Table 3 lists key diagnostic onset indicators for FXTAS that generally appear in men after the age of ≥50 years.21 These indicators, when combined with an observed decline of function, should lead the clinician to consider a differential diagnosis of FXTAS.
Summary of Diagnostic Overlap for Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS)
With the onset of FXTAS, initial symptoms such as an intention tremor or ataxia correlate with declining ambulation or fine motor function.9 Impaired executive function also may be noted. Onset is insidious. Any of these symptoms may appear several years before general decline of function. Eventually, decline results in loss of mobility, inability to carry out activities of daily living skills, and ultimately wheelchair dependence. The person may go on to experience multiple body system impairments, including lower extremity pain, hypertension or orthostatic hypotension, urinary or bowel incontinence, autonomic dysfunction including impotence, and, in later stages, swallowing dysfunction.9,19
Cognitive changes often appear concurrently with initial body function impairments and include memory problems, mood swings, and executive function deficits. Premutation carriers are known to frequently have a documented history of psychiatric symptoms in childhood that may include ADHD, anxiety, shyness or obsessive-compulsive behaviors, and ASD.22,39
Significant central nervous system findings in FXTAS that highly correlate with CGG repeat length are white matter lesions (ie, high-signal [T2-weighted] lesions in the middle cerebellar peduncles) and generalized brain atrophy.9,26 These brain changes are noted to increase with age.40
The identification of mitochondrial dysfunction in the brain and fibroblasts has been described in some patients with FXTAS.41(p550) This finding may be clinically relevant, as some of the body system impairments found in FXTAS (eg, dysautonomia, peripheral neuropathy, fatigue, weakness, exercise intolerance) are noted to overlap with another category of health conditions (ie, mitochondrial respiratory chain diseases, characterized by mitochondrial dysfunction).41
Physical Therapy Management of Fragile X–Associated Disorders
The role of physical therapy in the management of genetic neurodegenerative disorders, of which the FXD group is but one of more than 600 known to date, has yet to be clearly defined and definitively researched.42 Recently, literature has begun to appear that addresses physical therapy effectiveness for some specific genetic neurodegenerative disorders.43–50 These articles, as a group, represent a small body of evidence regarding the efficacy of physical therapy in addressing the health conditions and related body function, activity, and participation limitations that may appear similar phenotypically and even clinically, but individually represent distinct genetic conditions.51 Available evidence related to interventions appropriate to FXD is, as yet, lacking.52
Initial definitions and descriptions of FXD are primarily found in the genetic and psychiatric literature. More recently, the significance of the movement disorders typical for FXD also has been identified and described in the movement disorder literature.53 Although patients with FXD may be seen by a physical therapist at any point over their life span for a movement or musculoskeletal condition, treatment often is provided without documentation of an FXD diagnosis. A referral for physical therapy is typically made with a diagnosis such as “ataxia, unknown etiology.” Misdiagnosis, as discussed by Saul and Tarleton4 specifically in relation to FXTAS, is a major issue. When reviewing 56 individuals with FXTAS, Saul and Tarleton's team found that the group had 98 different non-fragile X–related diagnoses prior to receiving the diagnosis of FXTAS.4
To serve this patient population, the physical therapist will need to apply skills in understanding the genetic conditions that lead to structural brain changes that result in cognitive, cardiac, sensory, and motor impairments and limitations in activity and participation.53 The physical therapist brings an understanding of movement disorders. This knowledge can be applied to choose strategies to assess and plan interventions to develop, preserve, or restore activity and mitigate participation limitations. A short list of Web-based resources for the assessment of ataxia and balance is presented in the eTable. Clearly, goals of therapy would be to slow down or minimize evident activity limitations and to optimize participation. However, currently available information regarding effective physical therapy intervention is, at best, at a symptomatic level.
The development of an intervention plan that addresses the identified impairments, activity limitations, and participation barriers will be specific for each FXD condition. Special considerations listed by diagnosis in Table 4 are included to help the therapist identify the individual characteristics for each of the 3 FXD conditions.11
Special Characteristics of Fragile X–Associated Disorders for Treatment Consideration by Physical Therapy Divided by Individual Disorder
Fragile X Syndrome
There is minimal written information regarding targeted physical therapy intervention for children with FXS. Nevertheless, therapists are treating children with FXS who may have a physical therapist diagnosis of developmental or motor delay. Thus, research on structuring intervention for the child diagnosed with FXS will be a welcome addition for the therapy community.
The goal of establishing an intervention baseline with an emphasis on the musculoskeletal impairments listed in Table 2 should be included in the physical therapy assessment of a child with FXS.1 The health care supervision document for the child with FXS, developed by the American Academy of Pediatrics, provides additional health information for intervention planning.54
When delayed walking skills are identified in a young child, a referral for physical therapy is likely to address this developmental domain, and the therapist then has a role in the development of functional skills to achieve community mobility. Physical therapists can be instrumental in identifying intervention strategies related to balance, motor control, and sensory regulation.55–57
The assessment for and recommendation of assistive devices is an additional area that physical therapy can address. At a young age, a child with FXS may benefit from a stroller or chair adaptation for increased sitting support or could require an assistive device for walking or an adapted tricycle for better mobility. Many children with FXS have severe foot pronation secondary to low muscle tone and ligamentous laxity that contributes to poor stability in early walking stages.29 Advice on shoewear or the need for orthotic intervention could be supportive in providing the child increased stability and appropriate biomechanical foot alignment during ambulation.58
The older child may experience activity limitations, including reduced endurance or limited community ambulation, related to low muscle tone or secondary cardiac impairments (specifically, a risk for mitral valve prolapse).59 Thus, it is clear that, for this population, participation limitations may be a reality for several reasons. However, the physical therapist can influence participation level by structuring skill development or introducing assistive technology to optimize function.
Fragile X–Associated Primary Ovarian Insufficiency Syndrome
For the purpose of this perspective article, the discussion of physical therapist management of FXPOI will be specifically directed at the female premutation carrier of the FMR1 gene and without including FXTAS, which will be discussed in the Fragile X–Associated Tremor/Ataxia Syndrome section.
Based on the now known underlying cellular pathology, the female premutation carrier is at risk for developing a range of musculoskeletal, neurological, or cardiac (hypertension) problems and may have sought out physical therapy treatment for a range of physical symptoms.22 The treating therapist, therefore, must be aware of and alert to those characteristics that provide clues that the underlying etiology is FXPOI.
The physical therapist will treat the patient by addressing a physical therapist diagnosis, which may be an impairment or function and participation limitation. For people with FXPOI, symptoms can be vague and inconsistent, but lower extremity pain and fibromyalgia are common.23
A comprehensive medical history is essential to the physical therapist examination, which can inform medical diagnosis. Asking about genetic disorders in the family and offspring may shed light on diagnosis and management. In treating female patients who are premutation carriers and, therefore, at risk for FXPOI, the therapist should be aware of some issues unique to this group, such as muscle pain, fibromyalgia, and increased anxiety related to this diagnosis.53
Fragile X–Associated Tremor/Ataxia Syndrome
Physical therapy in the management of FXTAS is typically symptomatic and should address functional limitations and sustain or improve fitness. Of particular concern is maintaining strength and preventing falls secondary to increasing ataxia and parkinsonism, as is characteristic of FXTAS.9,53 Furthermore, the therapist must consider possible comorbidities that could include the impact of normal aging or secondary conditions that may befall an individual. Thus, the task for the physical therapist must be to systematically apply a process of patient and client management. As defined in the Guide 3.0, this process includes a systems review and complete evaluation.7
Although evidence regarding the application of therapeutic intervention for FXTAS in general is still primarily at an individual case level, there is some support in the literature related to the effectiveness of body-weight–supported treadmill training9 and exercise in reducing depression, anxiety, and other behavioral issues.34 Still lacking is a delineation of appropriate exercise training protocols. With exercise, choosing to apply low-impact versus high-impact routines for people with FXTAS has yet to be established in the literature.
Fragile X–associated tremor/ataxia syndrome is a specific example of a late-onset neurodegenerative movement disorder that can be expected to have a predictable natural progression. The stages of motor impairment in FXTAS initially were empirically defined by Bacalman et al60 and have been updated by Muzar and Lozano.61 The 6-point scale defines 6 levels of evolving movement impairments and relates them to functional impact and activity limitations in activities of daily living.9 Beyond the consideration of evolving motor impairment and genetic test results, a conclusive diagnosis of FXTAS would include definitive neuroradiological findings as well as clinical criteria.2
Implications for Practice
The 3 faces of FXD are often underrecognized by physical therapists and underdiagnosed by the medical community. Although the incidence of FXS as a full mutation with intellectual delay and, in some cases, ASD, is estimated to occur at approximately 1:4,000 in men and 1:6,000 in women, the actual range of involvement and clinical consequences is much larger when physical, learning, and behavioral problems of all FXD carriers are included.9 Possibly, many individuals carrying the FMR1 gene are being treated by physical therapists for impairments of the musculoskeletal system or followed by therapists in movement disorder clinics without a clear etiology or medical diagnosis.
The intergenerational and life-span nature of FXD should underscore for therapists the importance of taking a good family history. Family history taking could be adding to the evaluation process a genetic tool that is free and readily available.62 The genetic basis of FXD clearly demonstrates the relevance of obtaining a family history and exploring the health status of family members over multiple generations.
The Guide 3.0 (chapter 4) establishes the standard of including a family history in every evaluation.7 The US Surgeon General has made family history taking a national health priority.63 The Centers for Disease Control and Prevention created a free Web-based tool (https://familyhistory.hhs.gov/) for families to collect and store relevant health history facts.
The topic of newborn screening for fragile X also should be considered. Newborn screening for fragile X (technically of the FMR1 gene) is not included in mandated newborn screening programs in any US state. Adding fragile X screening to a state screening protocol would need to be considered by each state individually.
The efficacy of fragile X testing in the newborn is controversial, as there is yet no treatment for the condition.64 In a survey of 140 parents of children with FXS, 43% reported the birth of a second child before their first child was given a diagnosis of FXS. The median age of diagnosis was reported as 26 months (range=6–101).64
Gutiérrez et al65 support the value of screening for FXS, as it allows identification of a risk factor before the birth of any children or possibly the birth of a second affected child. With a negative screen, the family has no risk for FXS.65 Two arguments against fragile X screening are: (1) the absence of any known treatment for this genetic condition and (2) the potential for added stress on families when this condition is identified.66 The 2009 Cochrane review comparing prenatal and antenatal screening for FXS supports that there is currently no evidence regarding the benefits of nonselective screening for all newborns.67
Both physical therapists and physicians need information on intervention approaches that would be optimal for FXD in order to improve early intervention and life-span management. The evidence suggests that the physical therapy profession has shown a limited commitment to linking an accurate etiology to the clinical management. Guccione recognized this paradox, as follows:
The scientific basis for exercise as a preventive measure and as an intervention for the impairments of chronic diseases has never been stronger. Yet, despite our rhetoric to the contrary, we substantially ignore topics such as diabetes, arthritis, and neurodegenerative diseases (author's italics) from a population-based perspective.42(p1684)
The urgent need for physical therapists to identify and understand neurodegenerative disorders cannot be overstated. Approximately 1 million people carry the FMR1 gene. When the frequency of FXD is combined with the premutation carrier rate of ±1:300 for men and women, a large group of patients in need of physical therapist services exists.9
Summary and Recommendations
A group of FXDs that includes 3 separate health conditions (FXS, FXPOI, and FXTAS) has only recently been identified as distinct and differentiated from the larger category of neurodegenerative disorders. Fragile X syndrome represents the most common cause of inherited intellectual disability, and carriers of expanded CGG repeats have a high chance of developing a late-onset neurodegenerative condition. In view of the number of neurodegenerative disorders that are typically treated by physical therapists, it appears imperative to prioritize increasing physical therapists' appreciation of the role that genetics plays and to add a goal to develop the screening and clinical management tools for conditions such as FXD.
Recommendations are made for research to develop targeted interventions and strengthen the role of the physical therapists as part of the patient management team. For FXD, physical therapists should:
Recognize the relevance of understanding the genetics and advocate for appropriate screening of FXD.
Increase their understanding of and learn how to take a complete family history of all patients with a movement impairment.
Advocate for early intervention services for infants and toddlers with FXS and document the efficacy of applicable intervention strategies for this population.
Demonstrate intervention efficacy and move to development of intervention guidelines to address the issues related to FXD.
Gain an understanding of and develop more tools to optimally support individuals with FXD across the life span.
Identify treatment strategies for patients with FXD to minimize secondary impairments.
Participate in research to identify novel approaches for treatment of FXD and other neurodegenerative disorders.
Footnotes
The author acknowledges Randi J. Hagerman, MD, University of California–Davis M.I.N.D. Institute, for sharing her expertise, medical, and clinical knowledge and dedication to support educating the health professional team for the benefit of patients.
Dr Lieb-Lundell is a Pediatric Certified Specialist.
The author also acknowledges Marilyn Miller, PT, PhD, for her encouragement and editorial support; Nancy E. Byl, PT, PhD, FAPTA, for her support to maintain highest professional standards in the written language; and Barbara Connolly, PT, DPT, EdD, FAPTA, for her insight and editorial support.
This article was written in partial fulfillment of Dr Lieb-Lundell's DPT degree at the University of St Augustine for Health Sciences in San Marcos, California.
- Received October 9, 2014.
- Accepted May 9, 2016.
- © 2016 American Physical Therapy Association
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