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

Children and Adults: High arched palate and dental malocclusion are common

Refer to a dentist for a semi-annual exam

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

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

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

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

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

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

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

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)

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

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