SMS Medical Management Guidelines
Management involves evaluation for manifestations of SMS and treatment to mitigate symptoms. These guidelines were developed and approved by PRISMS Professional Advisory Board. They are published as part of the in-depth review of SMS that appears in GeneReviews. (Last update June 2012)
Evaluations Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with Smith-Magenis syndrome (SMS), the following evaluations are recommended:
- Complete review of systems at the time of diagnosis
- Physical and neurologic examination
- Renal ultrasound examination to evaluate for possible renal/urologic anomalies (~20% of individuals with SMS), including urologic workup if a history of frequent urinary tract infections exists
- Echocardiogram to evaluate for possible cardiac anomalies (<45% of individuals with SMS); follow-up depending on the severity of any cardiac anomaly identified
- Spine radiographs to evaluate for possible vertebral anomalies and scoliosis (~60%)
- Routine blood chemistries, qualitative immunoglobulins, fasting lipid profile (evaluation for hypercholesterolemia), and thyroid function studies
- Ophthalmologic evaluation with attention to evidence of strabismus, microcornea, iris anomalies, and refractive error
- Comprehensive speech/language pathology evaluation
- Assessment of caloric intake, signs and symptoms of gastroesophageal reflux disease (GERD), swallowing abilities, and oral motor skills with referral as warranted for full diagnostic evaluation
- Otolaryngologic evaluation to assess ear, nose, and throat problems, with specific attention to ear physiology and palatal abnormalities (clefting, velopharyngeal insufficiency)
- Audiologic evaluation at regular intervals to monitor for conductive and/or sensorineural hearing loss
- Multidisciplinary developmental evaluation, including assessment of motor, speech, language, personal-social, general cognitive, and vocational skills
- Early evaluation by physical and/or occupational therapists
- Sleep history with particular attention to sleep/wake schedules and respiratory function. Sleep diaries may prove helpful in documenting sleep/wake schedules. Evidence of sleep-disordered breathing warrants a polysomnogram (overnight sleep study) to evaluate for obstructive sleep apnea.
- EEG in individuals who have clinical seizures to guide the choice of antiepileptic agents. For those without overt seizures, EEG may be helpful to evaluate for possible subclinical events in which treatment may improve attention and/or behavior; a change in behavior or attention warrants reevaluation.
- Neuroimaging (MRI or CT scan) in accordance with findings such as seizures and/or motor asymmetry
- In individuals with SMS documented to have larger deletions extending into 17p12:
- Specific screening for adrenal function
- Detailed assessment and attention to peripheral neurologic function in individuals with SMS with large deletions involving PMP22, which is associated with hereditary neuropathy with liability to pressure palsy (HNPP)
- Assessment of family support and psychosocial and emotional needs to assist in designing family interventions
- Medical genetics consultation
Treatment of Manifestations
The following are appropriate:
- Ongoing pediatric care with regular immunizations
- From early infancy, referrals for early childhood intervention programs, followed by ongoing special education programs and vocational training in later years
- Therapies including speech/language, physical, occupational, and especially sensory integration:
- During early childhood, speech/language pathology services should initially focus on identifying and treating swallowing and feeding problems as well as optimizing oral sensorimotor development.
- Therapeutic goals of increasing sensory input, fostering movement of the articulators, increasing oral motor endurance, and decreasing hypersensitivity are needed to develop skills related to swallowing and speech production.
- The use of sign language and total communication programs, such as computer assisted devices and tablets, as adjuncts to traditional speech/language therapy are felt to improve communication skills and also to have a positive impact on behavior. The ability to develop expressive language appears dependent on the early use of sign language and intervention by speech/language pathologists.
- Atypical patterns of sensory processing may become more prominent with increased age. Insight about the vulnerabilities and relative strengths in patterns of sensory processing may aid caregivers of individuals with SMS in adapting activity demands, modifying the environment, and facilitating appropriate and supportive social interactions. In addition, the potential for more problematic or atypical behaviors with increased age underscores the need for early and ongoing intervention and caregiver education. [Hildenbrand & Smith 2012].
- A comprehensive behavior support plan for home and school should be considered as soon as problem behaviors arise, typically starting in early elementary school. A structured school program with one-on-one support and curricula matched to the known cognitive and behavioral profile of SMS can be effective in addressing the needs of these students.
- The combination of intellectual disability, severe behavioral abnormalities, and sleep disturbance takes a significant toll on parents and siblings. Parents report high rates of depression and anxiety, and family stress is significantly higher in families of people with SMS than in those of children with nonspecific developmental disabilities [Hodapp et al 1998, Foster et al 2010]. Family support services and resources should be included as essential components of a holistic management plan for people with SMS.
- Use of psychotropic medication to increase attention and/or decrease hyperactivity. No single regimen shows consistent efficacy [Laje et al 2010a]. Based on an extensive review of psychotropic medication use in a large cohort of individuals with SMS (n=62), use of polypharmacy and/or serial trials with minimal effectiveness was observed. Benzodiazepines obtained the lowest mean efficacy score in the "slightly worse" range, suggesting that use of these drugs may be detrimental to individuals with SMS [Laje et al 2010a].
- Behavioral therapies including special education techniques that emphasize individualized instruction, structure, and routine to help minimize behavioral outbursts in the school setting
- Therapeutic management of the sleep disorder. Sleep management in SMS remains a challenge for physicians and parents. No well-controlled treatment trials have been reported:
- Early anecdotal reports of therapeutic benefit from melatonin taken at bedtime remain encouraging, providing variable improvement of sleep without reports of major adverse reactions. Dosages should be kept low (≤3 mg). However, melatonin dispensed over the counter is not regulated by the FDA; thus, dosages may not be exact. No early and controlled melatonin treatment trials have been conducted. A monitored trial of four to six weeks on melatonin may be worth considering in affected individuals with sleep disturbance.
- A single uncontrolled study of nine individuals with SMS treated with oral ß-1-adrenergic antagonists (acebutolol 10 mg/kg) reported suppression of daytime melatonin peaks and subjectively improved behavior [De Leersnyder et al 2001]. This treatment, however, did not restore nocturnal plasma concentration of melatonin.
- A second uncontrolled trial by the same group [De Leersnyder et al 2003] combined the daytime dose of acebutolol with an evening oral dose of melatonin (6 mg at 8pm) and found that nocturnal plasma concentration of melatonin was restored and nighttime sleep improved with disappearance of nocturnal awakenings. Parents also reported subjective improvement in daytime behaviors with increased concentration. Contraindications to the use of ß-1-adrenergic antagonists include asthma, pulmonary problems, some cardiovascular disease, and diabetes mellitus.
- Prior to beginning any trial, the child's medical status and baseline sleep pattern must be considered.
- Enclosed bed system for containment during sleep
- Respite care and family psychosocial support to help assure the optimal environment for the affected individual
- Monitoring of hypercholesterolemia (recognized in >50% of individuals with SMS); treatment with diet or medication as indicated
- Treatment with corrective lenses as indicated for ophthalmologic abnormalities
- Treatment of recurrent otitis media with tympanostomy tubes as needed
- Auditory amplification if hearing loss is identified
- Management of seizures in accordance with standard practice
- Treatment of cardiac and renal anomalies and scoliosis in accordance with standard medical care. While growth hormone treatment has been reported [Itoh et al 2004, Spadoni et al 2004], controlled studies have not evaluated its effectiveness.
- Multidisciplinary team evaluation (including physical, occupational, and speech therapy evaluations and pediatric assessment) to assist in development of an individualized educational program (IEP). Periodic neurodevelopmental assessments and/or developmental/behavioral pediatric consultation can be an important adjunct to the team evaluation.
- Thyroid function, including free T4 and TSH
- Fasting lipid profile
- Routine urinalysis to evaluate for occult urinary tract infections
- Monitoring for scoliosis
- Ophthalmologic evaluation
- Otolaryngologic follow-up for assessment and management of otitis media and other sinus abnormalities
- Audiologic evaluation to monitor for conductive or sensorineural hearing loss annually or as clinically indicated
Agents/Circumstances to Avoid
In at least one case, a teenage female with SMS was documented to have a serious adverse event taking Strattera® (atomoxetine hydrochloride) with extreme escalation of behaviors and aggression leading to hospitalization. Significant changes in her sleep pattern were also documented. Care should be taken to track sleep parameters and behavior with this medication.
Ann CM Smith, MA, DSc (hon), CGC
Kerry E Boyd, MD, FRCP(C)
Sarah H Elsea, PhD, FACMG
Brenda M Finucane, MS, CGC
Barbara Haas-Givler, MEd, BCBA
Andrea Gropman, MD, FAAP, FACMG
Gonzalo Laje, MD
Ellen Magenis, MD, FAAP, FACMG
Lorraine Potocki, MD, FACMG
Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1310/