Chromosome 15q11.2-13.1 duplication syndrome (dup15q) is a clinically identifiable syndrome resulting from duplication of chromosome 15q11.2-13.1.  These duplications most commonly occur in one of two forms, either an extra isodicentric 15 chromosome, abbreviated idic(15), or an interstitial duplication 15, abbreviated int dup(15).  Those with idic(15) have 2 extra copies but those with int dup(15) have only one extra copy resulting in milder symptoms than idic(15).  There is a wide range in the severity of characteristics found in dup15q syndrome.  However, common characteristics often include developmental delay, seizures [in idic(15)], hypotonia, intellectual disability, absent or poor language, and autistic behavior.

Approximately 400 families were contacted through the Dup15q Alliance and asked to complete a questionnaire survey online regarding the presence and presentation of epilepsy in their family members with a chromosome 15q duplication.  There were responses from 95 family members of individuals with chromosome 15q duplications, representing a response rate of ~25% of the entire Dup15q Alliance in 2009.  There were 12 individuals (5 male, 7 female) with int dup(15) and the remaining 83 had some variation of a marker idic(15) chromosome.

Seizure Types

For those with int dup(15), only 3 (25%) of 12 had seizures with one of the three reporting only a single seizure.  This seizure rate is similar to that reported in the autistic spectrum population in general.  The seizure rate for those with idic(15) was much higher as 63% had seizures.  The seizure severity was also generally increased in idic(15) compared to (15).  Out of those with(15) and seizures, 81% had multiple seizure types.  The most common seizure type was generalized tonic-clonic (60% – also called “grand mal” seizures and consist of loss of consciousness with shaking of arms and legs).  Other common seizure types were atonic (40% – these are brief head drops or drops to the floor), myoclonic (40% – very quick “lightning-like jerks”), focal onset (40% – seizures that start on one side of the body or face), tonic (38% – presents as stiffening) and absence (31% – presents as staring spells).

Important points:

  • 63 % of those with idic(15) had seizures, compared to 25% of int dup(15).
  • Most of those with idic(15) had multiple seizure types, with generalized tonic-clonic being the most common.

Seizures Across the Lifespan

Active seizures (which are defined as having a seizure in the past year) may increase with age.  The rate of active seizures was 14% in children under 3, compared to 68% in those over 18 years old.  With puberty, 65% of respondents experienced a worsening of seizures, 18% had improvement and 18% had no significant changes.  This may not accurately represent the rate of seizures in adolescents/young adults as there were not many included in the survey.  Status epilepticus (prolonged seizure lasting more than 15 minutes) was reported in 33% of respondents and 67% reported at least one hospitalization due to seizures.  Developmental regressions were reported in 63% of respondents, with 61% of those attributing these episodes of regression to frequent or prolonged seizure activity.

Important points:

  • The rate of dup15q individuals with active seizures appears to increase with age, but this may not accurately reflect the rate of seizures in adolescents/young adults.
  • There was a worsening of seizures with puberty in 65% of respondents.
  • Developmental regressions were reported in 63% of respondents and were frequently attributed to seizure activity.

Infantile Spasms

Of note, 42% of those who had seizures in idic(15) reported a history of a specific type of seizure called infantile spasms.  Infantile spasms usually begin in the first year of life.  They are often characterized by a sudden bending forward of the body with stiffening of the arms and legs and may occur in clusters.  Some children will arch their backs as they extend their arms and legs.  Infantile spasms tend to occur after awakening or feeding.  The average age of onset was 6-7 months and the average duration the spasms lasted was nearly 1 year.  Spasms typically resolved before 3 years of age.

Infantile spasms were the first seizure type for all 22 individuals who had them.  Afterward, 91% of them went on to develop other seizure types, including tonic (58%), atonic (46%), myoclonic (42%) and atypical absence (42%).

Children with dup15q syndrome who have epilepsy, particularly those with infantile spasms are likely to have a greater level of impairment in terms of cognitive and adaptive functioning relative to those without epilepsy. Identifying and controlling seizures early could be extremely beneficial for children with dup15q syndrome.

The 2 most common treatments for the 22 children with infantile spasms were ACTH/prednisone and vigabatrin.  The only other medications used by more than one respondent were valproic acid and topiramate.  ACTH/prednisone was significantly more effective than vigabatrin in controlling seizures (75% for ACTH/prednisone vs 29% for vigabatrin).

Important points:

  • Infantile spasms are a common seizure type in idic(15).
  • On average, infantile spasms begin at 6-7 months and resolve before 3 years of age.
  • Children with infantile spasms often go on to develop other seizure types.
  • ACTH/prednisone is much more effective than vigabatrin in treating infantile spasms.
  • Infantile Spasms Clinical Decision Tree

Treatment of Seizures

Epilepsy in those individuals with idic(15) often does not respond to medication.  Only 24% of the respondents reported a >90% seizure reduction from the first medication, sustained over a period of at least 1 year.  An additional 21% showed a 50-90% seizure improvement, sustained over 1 year with the first medication. For the second medication prescribed, there was a 36% response rate.

The most commonly prescribed medications were valproic acid (Depakote – 60%), levetiracetam (Keppra – 44%), lamotrigine (Lamictal – 37%), carbamazepine (Tegretol – 35%), zonisamide (Zonegran – 23%) and clonazepam (Klonopin – 23%).

Family members were asked which medications they thought were most effective at controlling seizures.  Rufinamide (Banzel – 67%) was thought to be most effective, followed by carbamazepine (Tegretol – 44%), lamotrigine (Lamictal – 37%), oxcarbazepine (Trileptal – 33%) and valproic acid (Depakote – 32%).  Less than 5% of those asked thought that benzodiazepines (such as clonazepam) were an effective treatment for seizures.

At the time of the study, the percentage of people who were still taking the medication was highest in rufinamide (100%), followed by lamotrigine (53%), valproic acid (45%), and zonisamide (42%).  Intolerable side effects were most common in levetiracetam (Keppra – 52%, behavioral), zonisamide (Zonegran – 50%, sedation), clobazam (Onfi – 50%, sedation), oxcarbazepine (Trileptal – 50%, sedation) and topiramate (Topamax – 48%, sedation).

Only a few respondents had family members who tried non-medication treatments, such as the ketogenic diet, vagus nerve stimulation, gluten-free diet, and surgical resection.  Not enough data were available to make any conclusions about the effectiveness or tolerability of these treatments.

Important points:

  • Seizures often do not respond well to medications.
  • The most common medicines prescribed were Depakote, Keppra, Lamictal, and Tegretol.
  • The most effective medicines reported were Banzel, Tegretol, Lamictal, Trileptal, and Depakote.
  • Benzodiazepines alone do not seem to be effective at treating seizures.
  • Side effects were most common in Keppra, Zonegran, Onfi, Trileptal, and Topamax.

Developmental and Epileptic Encephalopathies

Some individuals with dup15q syndrome may also be considered to have a Developmental Epileptic Encephalopathy. Developmental and Epileptic Encephalopathy (DEE) refers to a group of severe epilepsies that are characterized both by seizures, which are often drug-resistant, as well as encephalopathy, which is a term used to describe significant developmental delay or even loss of developmental skills. Neurodevelopmental impairment is common, affecting cognition, communication, attention, behavior, and sleep. The underlying etiology of the syndrome can be a cause of the neurodevelopmental impairment, while seizures themselves can also have an adverse impact.

Important points:

  • Patients with developmental and epileptic encephalopathies have significant neurodevelopmental comorbidities including cognitive, behavioral, psychiatric, and sleep impairments.
  • Some anti-seizure medications have side effects that may contribute to these impairments, including levetiracetam and perampanel (aggressiveness and irritability), topiramate and zonisamide (language and memory problems), and lamotrigine (insomnia).
  • Cannabidiol, fenfluramine, levetiracetam, brivaracetam, and lamotrigine may have positive effects on some aspects of cognition.

Psychobehavioral and Cognitive Adverse Events of Anit-Seizure Medications for the Treatment of Developmental and Epileptic encephalopathies.


This is the largest study to date examining epilepsy and its treatments in Dup15q syndrome.  Epilepsy is common in idic(15) with a high prevalence of infantile spasms and is typically resistant to medication.  Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population.  For infantile spasms, ATCH/prednisone treatment appears to be much more effective than vigabatrin.  For other seizure types, Banzel, Tegretol, Lamictal, Trileptal, and Depakote were reported as the most effective medications but the study is not large enough to say this definitively.  In general, it appears that GABAergic medications, such as benzodiazepines and vigabatrin, may not be effective in treating seizures.  This may be related to the duplicated GABA receptors in dup15q.  This study did have some limitations because it was a questionnaire based-study that relied on family reporting and was subject to more responses from families dealing with more difficult seizures.  Hopefully, larger studies will available in the future to gain a better understanding of epilepsy in dup15q syndrome and ultimately lead to better approaches to effective treatment.

New Seizure Medications

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Devices & Technology

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