Development
Development is usually normal prior to 18 months of age, although subtle delays may be appreciated prior to that time in a minority of cases (PHYSICIANS: n = 20, 90%;
caregivers
: n = 10, 70%).
Subtle delays are typically evident between 18 and 36 months (PHYSICIANS: n = 19, 100%;
caregivers
: n = 9, 78%).
Intellectual disability (developmental quotient < 70) is present in most children aged 3 year and older (PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 89%).
Degree of intellectual disability worsens with time, with most young adults having moderate to severe intellectual disability (PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 89%).
Most children exhibit stagnation (lack of or slower progression) as opposed to true regression (loss of skills; PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 89%).
Encephalopathy and regression can occur following a bout of prolonged febrile status epilepticus in a minority of cases (PHYSICIANS: n = 19, 100%;
caregivers
: n = 9, 78%).
Social skills are better preserved than communication skills (PHYSICIANS: n = 18, 83%; caregivers: n = 9, 44%).
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The following factors are correlated with poor developmental outcome:
Younger age at onset of DS (PHYSICIANS: n = 18, 89%;
caregivers
: n = 9, 78%)
Greater number of convulsive status epilepticus (>30 min) episodes (PHYSICIANS: n = 19, 95%;
caregivers
: n = 9, 78%)
Greater duration of longest convulsive status epilepticus event (PHYSICIANS: n = 17, 82%;
caregivers
: n = 9, 78%)
Longer use of contraindicated medications (i.e., sodium channel blockers including lamotrigine) in early life (PHYSICIANS: n = 18, 83%; CAREGIVERS: n = 8, 100%)
Delay in use of optimal therapies (PHYSICIANS: n = 18, 83%;
caregivers
: n = 9, 78%)
Appearance of absence and/or myoclonic seizures in the first year of life (PHYSICIANS: n = 16, 94%; CAREGIVERS: n = 7, 86%)
Appearance of tonic seizures ( physicians: n = 14, 57%; caregivers
a
: n = 4, 75%)
Higher frequency of interictal discharges on EEG if the first year of life ( PHYSICIANS: n = 14, 82%; caregivers
a
: n = 2, 100%)
Early motor delay (
physicians
: n = 19, 74%; caregivers: n = 9, 56%)
Greater number or longer episodes of nonconvulsive status epilepticus (physicians: n = 17, 59%;
caregivers
: n = 8, 75%)
Specific types of SCN1A variants (physicians: n = 18, 28%; caregivers: n = 7, 57%)
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Attention problems, autism, and behavior problems
Attention problems are present in most school‐aged children and teens with DS (PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 100%).
Stimulant medications are safe to use in persons with DS with significant attention problems ( PHYSICIANS: n = 18, 94%; caregivers
a
: n = 2, 100%).
Stimulant medications are effective in persons with DS with significant attention problems (
physicians
: n = 17, 76%; caregivers
a
: n = 3, 67%).
Internalizing behaviors (depression, anxiety) are seen in a minority of preschool children but become more common with age and are present in more than half of adults (PHYSICIANS: n = 18, 83%; CAREGIVERS: n = 8, 100%).
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Externalizing behaviors (aggression, impulsivity) are seen in more than half of persons at the following ages:
Preschool children (physicians: n = 18, 56%; CAREGIVERS: n = 7, 86%)
School‐aged children (
physicians
: n = 18, 67%; CAREGIVERS:
n = 7, 86%)
Teens (physicians: n = 18, 61%; CAREGIVERS: n = 7, 86%)
Adults (physicians: n = 13, 46%; caregivers: n = 7, 43%)
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Prevalence of autistic features in children with DS:
Preschool children:
physicians
: n = 18, 72% stated prevalence of autistic features was <50%; CAREGIVERS: n = 9, 89% stated prevalence of autistic features was >50%.
School‐aged children:
physicians
: n = 19, 68% stated prevalence of autistic features was <50%; CAREGIVERS, n = 8, 100% said prevalence of autistic features was >50%.
Children with DS are at risk of autism spectrum disorder and concerns may be more apparent to parents/caregivers than neurology providers. Providers should query families for these concerns at regular follow‐up visits (PHYSICIANS: n = 19, 84%; caregivers: n = 8, 60%).
Less than half of preschool and school‐aged children with DS have undergone a formal evaluation for autism (PHYSICIANS: n = 18, 83%; CAREGIVERS: n = 8, 100%).
Current resources limit the number of at‐risk children who undergo formal evaluation for autism, leading to probable underdiagnosis of autism in DS (PHYSICIANS: n = 19, 89%;
caregivers
: n = 10, 70%).
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Gait problems and parkinsonian features
Gait abnormalities including ataxia or crouch gait are noted in approximately half of school‐aged (age 6–11 years) children with DS (PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 89%).
Gait abnormalities are seen in the majority of teens and young adults with DS (PHYSICIANS: n = 18, 100%; CAREGIVERS: n = 9, 100%).
Parkinsonian features including bradykinesia, rigidity, parkinsonian gait (stooped, stiff, unsteady), and postural instability are seen in a majority of adults with DS; however, resting tremor is typically absent (PHYSICIANS: n = 13, 92%; CAREGIVERS: n = 7, 86%).
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Therapies prescribed for gait disorders:
Physiotherapy and/or occupational therapy prescribed by 12/18 physicians and used by 6/8 caregivers. Median benefit reported by physicians was 5 and by caregivers was 6, on a scale of 1–9, where 1 is no benefit and 9 is marked benefit.
Sinemet (physicians: only 6 had ever tried Sinemet and only 4 treated more than 5 patients. Of physicians who had tried Sinemet, median reported benefit was 5 on a scale of 1–9).
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Speech
Most/all children with DS should be routinely referred for speech assessment and therapy (PHYSICIANS: n = 19, 79%; CAREGIVERS: n = 8, 88%).
Speech therapy is at least moderately beneficial for teens and adults with DS (physicians: n = 15, median score of 6 on a scale of 1–9; caregivers: n = 9, median score of 7 on a scale of 1–9).
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Sleep problems
Sleep problems are seen in a majority of persons with DS and can include increased nocturnal wakening, snoring, insomnia, and/or excessive daytime somnolence (PHYSICIANS: n = 19, 100%; CAREGIVERS: n = 10, 90%).
Questions regarding sleep should be routinely asked as part of continuing care of a person with DS (PHYSICIANS: n = 19, 100%; CAREGIVERS: n = 8, 100%).
A formal sleep study should be considered if a clinical history of a possible sleep disorder is obtained (PHYSICIANS: n = 18, 89%;
caregivers
: n = 8, 75%).
Attention to sleep hygiene is important in managing sleep problems associated with DS (PHYSICIANS: n = 19, 100%; caregivers: n = 10, 60%).
Melatonin may be considered for persons with difficulty with initiating and maintaining sleep, but there are limited data on its efficacy (PHYSICIANS: n = 19, 100%; CAREGIVERS: n = 6, 100%).
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Benefits of melatonin for sleep:
18 physicians had experience using melatonin, median efficacy = 6.5 of 9 on a scale of 1–9, where 1 is no benefit and 9 is highly effective.
6 caregivers had experience with melatonin, median efficacy = 6.5 of 9.
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Benefits of clonidine for sleep:
7 physicians had experience using clonidine, median efficacy = 7 of 9.
3 caregivers had experience using clonidine, median efficacy = 6 of 9.
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Autonomic dysfunction
Routine cardiac testing is not required for persons with DS (
physicians
: n = 19, 79%).
There is no consistent therapy that is effective for dysautonomia (PHYSICIANS: n = 11, 82%).
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SUDEP
Persons with DS have a significant risk of SUDEP. Families must be made aware of this potential risk at diagnosis (PHYSICIANS: n = 19, 100%; CAREGIVERS: n = 9, 100%).
Risk of SUDEP will be at least mildly to moderately reduced due to recently approved seizure medications that have shown improved efficacy for DS (PHYSICIANS: n = 16, 88%; caregivers: n = 6, 50%)
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Use of monitoring devices for seizures:
68% of physicians did not routinely recommend the use of seizure monitoring devices for their patients with DS, but 74% would support a family's request for such a device.
31% of physicians reported that >50% of their patients used a seizure monitoring device.
67% of caregivers reported that >50% of persons with DS used a seizure monitoring device.
Effectiveness of monitoring devices for seizure detection was rated by physicians (n = 15) as 6 (IQR = 5–7) and by caregivers (n = 8) as 7 (IQR = 6–9) on a scale of 1–9, where 1 is ineffective and 9 is highly effective.
There was no consensus among physicians or caregivers that any particular monitoring device was more efficacious than another.
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Vaccinations
Persons with DS should receive all routine vaccinations (PHYSICIANS: n = 19, 84%;
caregivers
: n = 9, 78%).
Persons with DS should receive an annual influenza vaccination (
physicians
: n = 19, 79%;
caregivers
: n = 9, 78%).
Routine use of antipyretic medication around vaccinations should be considered to reduce likelihood of seizures (PHYSICIANS: n = 19, 95%; CAREGIVERS: n = 9, 89%).
Routine use of additional antiseizure medication (such as benzodiazepines) around vaccinations should be considered to reduce the likelihood of seizures (physicians: n = 19, 53%;
caregivers
: n = 9, 67% that this should NOT be done).
Persons with DS who are eligible should receive the COVID‐19 vaccination (PHYSICIANS: n = 19, 95%;
caregivers
: n = 9, 78%).
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Transition of care to adult neurology
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