Table 4.

Treatment of Manifestations in Individuals with Smith-Magenis Syndrome

Manifestation/ConcernTreatmentConsiderations/Other
Epilepsy Standard treatment w/ASM by an experienced neurologist
  • Many ASMs may be effective; none has been demonstrated effective specifically for SMS.
  • Education of parents/caregivers 1
Developmental delay /
Intellectual disability 		See Developmental Delay / Intellectual Disability Management Issues.
Speech/
Language delay
  • Identify & treat swallowing/feeding problems & optimize oral sensorimotor development.
  • Develop skills related to swallowing & speech production by ↑ sensory input, fostering movement of articulators, ↑ oral motor endurance, & ↓ hypersensitivity.
Behavior issues 2
  • Develop comprehensive behavior support plan for home & school at onset of maladaptive behaviors (typically starting in early elementary school).
  • Develop structured school program w/one-on-one support & curricula matched to known cognitive & behavior profile of SMS.
  • Behavioral therapies incl special education techniques emphasizing individualized instruction, structure, & routine to minimize behavioral outbursts in school
Insight about vulnerabilities & relative strengths in sensory processing patterns may aid caregivers in adapting activity demands, modifying environments, & facilitating appropriate & supportive social interactions. 3
Psychiatric
disorder 		Psychotropic medication & psychological services to ↓ maladaptive behaviors, ↑ attention &/or ↓ hyperactivity, ↓ anxiety, & stabilize mood.
  • Atypical patterns of sensory processing & more problematic/atypical behaviors may become more prominent w/↑ age.
  • No single medication regimen is consistently effective. 4
Sleep disorder 5 MelatoninEarly anecdotal reports of therapeutic benefit from melatonin (low dose; <3 mg) taken at bedtime suggest variable improvement of sleep w/o major adverse reactions. 6
TasimelteonMelatonin receptor agonist: first FDA-approved treatment of nighttime sleep disturbance in SMS. 7
Oral beta-1-adrenergic antagonistsA single uncontrolled study reported suppression of daytime melatonin peaks & subjectively improved behavior. 8
Acebutolol w/melatoninAn uncontrolled trial combined daytime dose of acebutolol w/evening oral dose of melatonin (6 mg at 8 pm) & found that nocturnal plasma concentration of melatonin was restored & nighttime sleep improved w/disappearance of nocturnal awakenings.9
Enclosed bed system for containment during sleep
Obesity Standard treatment 10Focus on staying active & fit starting at young age
Gastroesophageal
reflux disease 		Standard treatment
Constipation Standard treatment
Hypercholesterolemia Dietary modifications &/or medication in accordance w/standard practice
Palatal anomalies Standard treatmentConsideration of referral to multidisciplinary craniofacial clinic
Scoliosis Standard treatment per orthopedist
Ophthalmologic
abnormalities 		Standard treatment per ophthalmologist &/or optometrist
Recurrent otitis media Standard treatmentMay incl insertion of tympanostomy tubes
Hearing loss Hearing aids may be helpful; per otolaryngologist.Community hearing services through early intervention or school district
Cardiac anomalies Standard treatment
Renal anomalies Standard treatment
Mild immunodeficiency Standard treatmentMay incl prophylactic antibiotics
Hypothyroidism Thyroid replacement therapy
Growth hormone
deficiency 		Growth hormone treatmentGrowth hormone treatment has been reported; 11 controlled studies have not evaluated its efficacy.
Clinical manifestations
of BHD in those
w/FLCN deletion		See BHD, Treatment of Manifestations.
Impact on parents
& sibs 		Respite care, annual family psychosocial screenings, & family psychosocial support
  • Combination of ID, severe behavioral abnormalities, & sleep disturbance takes a significant toll on parents & sibs.
  • Incl family support services & resources as essential components of a holistic management plan.

ASM = anti-seizure medication; BHD = Birt-Hogg-Dubé syndrome; ID = intellectual disability; SMS = Smith-Magenis syndrome

1.

Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.

2.

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].

3.

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 w/nonspecific developmental disabilities [Hodapp et al 1998, Foster et al 2010].

4.

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].

5.

Sleep management is a challenge for physicians and parents. Prior to beginning any trial, a child's medical status and baseline sleep pattern must be considered.

6.

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.

7.
8.

Nine individuals with SMS were treated with oral beta-1-adrenergic antagonists (acebutolol 10 mg/kg) [De Leersnyder et al 2001]. This treatment, however, did not restore nocturnal plasma concentration of melatonin.

9.

Parents also reported subjective improvement in daytime behaviors with increased concentration. Contraindications to the use of beta-1-adrenergic antagonists include asthma, pulmonary problems, some cardiovascular disease, and diabetes mellitus.

10.

Dietary changes with portion management in addition to increased movement and physical activity, limiting sedentary activity, and discouraging nighttime eating

11.

From: Smith-Magenis Syndrome

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