HEALTH WATCH TABLE — Fragile X Syndrome

Considerations Recommendations
1. Head, eyes, ears, nose, throat
  • Children: Vision: strabismus, refractive errors are common
  • Hearing: recurrent otitis media is common
  • Nose: sinusitis is common
  • Undertake newborn vision and hearing screening and an auditory brainstem response (ABR)
  • Refer for a comprehensive ophthalmologic examination by 4 years of age
  • Visualize tympanic membranes at each visit
  • Adults: strabismus and refractive errors are common
  • Undertake hearing and vision screening at each visit with particular attention to myopia and hearing loss
2. Dental
  • Children and Adults: High arched palate and dental malocclusion are common
  • Refer to a dentist for a semi-annual exam
3. Cardiovascular
  • Children: Mitral valve prolapse (MVP) is less common in children (~10%) but may develop during adolescence
  • Auscultate for murmurs or clicks at each visit. If present, do an ECG and echocardiogram; refer to cardiologist, if indicated
  • Adults: MVP is common (~ 80%).
  • Aortic root dilation usually is not progressive
  • Hypertension is common and exacerbated by anxiety
  • Undertake an annual clinical exam. Based on findings, obtain an ECG and echocardiogram. Refer to cardiologist, as appropriate
  • Measure BP at each visit and at least annually
  • Treat hypertension when present
4. Sleep
  • Children and Adults: Obstructive sleep apnea (OSA) may be due to enlarged adenoids, hypotonia or connective tissue dysplasia
  • Sleep apnea is more common in individuals with Fragile X-associated tremor/ataxia syndrome
  • Children and Adults: Sleep-onset or sleep-maintenance insomnia is common
  • Ascertain a sleep history, examining bedtime, waketime, time needed to fall asleep and possible waking throughout the night
  • Assess for evidence of OSA
  • Refer to a sleep specialist, as appropriate
  • Behavioral sleep interventions or supplemental melatonin may be helpful
5. Gastrointestinal
  • Children: In infants, feeding problems are common with recurrent emesis associated with Gastroesophageal Reflux Disease (GERD) in ~ 30% of infants
  • Refer for assessment of GERD. Thickened liquids and upright positioning may be sufficient to manage GERD
6. Genitourinary
  • Children and Adults: Inguinal hernias are relatively common in males
  • Macroorchidism generally develops in late childhood and early adolescence and persists
  • Ureteral reflux may persist into adulthood
  • Assess for inguinal hernia annually beginning at age 1 year
  • Reassure patients and caregivers that macroorchidism does not require treatment
  • Monitor for signs of urinary tract infections (UTI), screen with urinalysis.
  • Evaluate recurring UTIs with cystourethrogram and renal ultrasound. Refer to a nephrologist.
  • Consider and assess for a renal etiology, such as scarring, as the basis for persistent hypertension
7. Sexual function
  • Adults: Males and females are fertile
  • Consider discussion of recurrence risk and reproductive options as a basis for referral to a geneticist. Make such a referral even if Fragile X is only suspected so that molecular testing can be undertaken in the person concerned and relevant family members
8. Musculoskeletal (MSK)
  • Children & Adults: Hyperextensible joints and pes planus are common. Scoliosis, clubfeet, joint dislocations (particularly congenital hip) may also occur
  • Undertake an MSK exam at birth, then at each regularly scheduled checkup
  • Elicit a history of possible dislocations
  • Refer to an orthopedic surgeon as dictated by clinical findings
  • Consider referral to a physical therapist (PT) or an occupational therapist (OT) to improve specific aspects of gross or fine motor skills if joint laxity or hypotonia interferes with function
  • Consider referring to a physiotherapist and podiatrist for orthotics
9. Neurology
  • Children & Adults: ~ 20% have epilepsy (may include generalized tonic-clonic seizures, staring spells, partial motor seizures, and temporal lobe seizures)
  • Hypotonia is common, in addition to fine and gross motor delays
  • Epilepsy occasionally persists into adulthood
  • Ascertain a history of seizures, which usually present in early childhood
  • Assess for atypical seizures in adulthood if suspicious findings occur or if intellectual function decreases
  • Arrange an EEG if epilepsy is suspected from the history
  • Refer to a neurologist as dictated by clinical findings

  
10. Behavioral/mental health
  • Children: 70% - 80% are hyperactive; ~ 30% have autism
  • Autistic-like features are common and may indicate concurrent autism spectrum disorder
  • Anxiety and mood disorders can also be present
  • Some features of autism, tantrums and aggression as well as anxiety and mood disorders may be treated with specific pharmacological agents
  • Sensory defensiveness is common and may trigger problem behaviors
  • Make an early referral to a clinical psychologist for essential parental teaching of appropriate behavior modification techniques following diagnosis
  • Hyperactivity may be managed using stimulant medications after age 5 years
  • Refer to an intensive behavioral intervention autism treatment program if autism spectrum disorder is present
  • Consider a referral to a psychiatrist for possible mental health disorders
  • Refer to a speech and language therapist following diagnosis
  • Adults: Aggressive behavior, sensory defensiveness, attention deficit hyperactivity disorder (ADHD), mood instability, and anxiety are common in adolescence and adulthood
  • Consider referral to a psychiatrist or psychologist to assess and manage possible mental health disorders
  • Violent outbursts may occur, especially in males, and may respond to behavioral and/or pharmacological measures (as for children)
11. Endocrine
  • Children: Precocious puberty may occur
  • Include attention in clinical examination to signs of precocious puberty in females.
  • Refer to an endocrinologist for consideration of use of a gonadotropin agonist to manage precocious puberty
  • Adults: Premenstrual symptoms (PMS) may be severe
  • Ascertain history of PMS with attention to menstruation, anxiety, depression, and mood lability. Consider an selective serotonin re-uptake inhibitor (SSRI)  to stabilize mood if PMS symptoms are severe enough
12. Other
  • Occasionally presents as Prader-Willi syndrome-like phenotype
  • Premutation Carriers:
  • A late onset tremor/ataxia syndrome has been reported in ~ 40% – 50% of male and ~ 8% of female Fragile X permutation carriers
  • Premature ovarian failure by age 45 has been reported in ~ 20% – 40% of female Fragile X permutation carriers
  • Psychiatric problems (e.g., mood and anxiety disorders) seem likely to occur in both male and female Fragile X premutation carriers 1, 2
  • For management of obesity and hyperphagia, consider approaches recommended for persons with Prader-Willi syndrome
  • Refer to appropriate specialists (e.g., neurologist, endocrinologist, psychiatrist) as indicated to assist in managing Prader-Willi syndrome-like symptoms
  • If premutation is suspected but not yet identified, order Fragile X DNA testing or refer to a genetics clinic
  • To manage depression or anxiety in premutation carriers, SSRIs, regular exercise and counseling have been helpful

 
Original tool: ©2011 Surrey Place Centre.
Developed by Forster-Gibson C, Berg J, & Developmental Disabilities Primary Care Initiative Co-editors.

Expert Clinician Reviewers
Thanks to the following clinicians for the review and helpful suggestions.

  • Randi Hagerman, MD
    Medical Director, M.I.N.D Institute
    Endowed Chair in Fragile X Research, School of Medicine,
    University of California, Davis, California
  • Carlo Paribello, MD
    Director, Fragile X Clinic, Surrey Place Centre, Toronto
    President and Medical Director, Fragile X Research Foundation of Canada

Modified with permission of Surrey Place Centre. This tool was reviewed and adapted for U.S. use by physicians on the Toolkit’s Advisory Committee; for list, view here.

Additional reviewer was Jeremy M. Veenstra-VanderWeele, M.D., Assistant Professor of Psychiatry, Pediatrics, and Pharmacology; Medical Director, Treatment and Research Institute for Autism Spectrum Disorders (TRIAD); Director, Fragile X Treatment Research Program; Director, Division of Child and Adolescent Psychiatry, Vanderbilt University, Nashville.

Resources

References

  1. Amiri K, Hagerman RJ, Hagerman PJ. Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. Arch Neurol 2008 Jan;65(1):19-25.
  2. Bourgeois JA, Coffey SM, Rivera SM, Hessl D, Gane LW, Tassone F, et al. A review of fragile X premutation disorders: expanding the psychiatric perspective. J Clin Psychiatry 2009 Jun;70(6):852-62.