Epilepsy and seizures in young people with 22q11.2 deletion syndrome: Prevalence and links with other neurodevelopmental disorders

Abstract

Summary Objective The true prevalence of epileptic seizures and epilepsy in 22q11.2 deletion syndrome (22q11.2DS) is unknown, because previous studies have relied on historical medical record review. Associations of epilepsy with other neurodevelopmental manifestations (eg, specific psychiatric diagnoses) remain unexplored. Methods The primary caregivers of 108 deletion carriers (mean age 13.6 years) and 60 control siblings (mean age 13.1 years) completed a validated epilepsy screening questionnaire. A subsample (n = 44) underwent a second assessment with interview, prolonged electroencephalography (EEG), and medical record and epileptologist review. Intelligence quotient (IQ), psychopathology, and other neurodevelopmental problems were examined using neurocognitive assessment and questionnaire/interview. Results Eleven percent (12/108) of deletion carriers had an epilepsy diagnosis (controls 0%, P = 0.004). Fifty‐seven of the remaining 96 deletion carriers (59.4%) had seizures or seizurelike symptoms (controls 13.3%, 8/60, P < 0.001). A febrile seizure was reported for 24.1% (26/107) of cases (controls 0%, P < 0.001). One deletion carrier with a clinical history of epilepsy was diagnosed with an additional type of unprovoked seizure during the second assessment. One deletion carrier was newly diagnosed with epilepsy, and two more with possible nonmotor absence seizures. A positive screen on the epilepsy questionnaire was more likely in deletion carriers with lower performance IQ (odds ratio [OR] 0.96, P = 0.018), attention‐deficit/hyperactivity disorder (ADHD) (OR 3.28, P = 0.021), autism symptoms (OR 3.86, P = 0.004), and indicative motor coordination disorder (OR 4.56, P = 0.021). Significance Even when accounting for deletion carriers diagnosed with epilepsy, reports of seizures and seizurelike symptoms are common. These may be “true” epileptic seizures in some cases, which are not recognized during routine clinical care. Febrile seizures were far more common in deletion carriers compared to known population risk. A propensity for seizures in 22q11.2DS was associated with cognitive impairment, psychopathology, and motor coordination problems. Future research is required to determine whether this reflects common neurobiologic risk pathways or is a consequence of recurrent seizures.

The psychiatric phenotypes of 1q21 distal deletion and duplication

“…This represents an Table 2 The prevalence of psychiatric diagnoses in adults with 1q21 deletion or duplication and for adult controls. understudied topic in CNV research: however, a recent study has indicated that the frequency of seizures in young people with 22q11.2 deletion syndrome may be higher than suspected 35 , indicating that individuals with certain CNVs may need to be closely monitored and particularly under certain circumstances (e.g., fever). The one mirror phenotype of head size associated with this locus 6 was confirmed in our study.…”

Response to letter to editor: “Knowing when and how to use epilepsy screening questionnaires”

“…We are very grateful for the opportunity to reply to Dr Brunklaus’ letter regarding our paper “Epilepsy and seizures in young people with 22q11.2 deletion syndrome: Prevalence and links with other neurodevelopmental disorders.” We entirely agree that epilepsy is a clinical diagnosis and one that can be challenging to make with certainty—even in the optimal diagnostic environment.…”

“…We went to great lengths to report the limitations of the ESQ in our article and agree that the rate of misdiagnosis—particularly for symptoms such as “staring into space”— will be much higher in cases than in controls. We do not feel, however, that this can explain the novel and interesting finding of an elevated rate of febrile seizures in children and adolescents with 22q11.2 deletion syndrome (22q11.2 DS; 24% in cases, 0% in sibling controls) …”

Epilepsy, neuropsychiatric phenotypes, neuroimaging findings, and genotype-neurophenotype correlation in 22q11.2 deletion syndrome

“…The previous studies have shown that the prevalence of epilepsy in 22q11.2 DS ranges from 4.4% to 36.8%. 6 In addition, approximately 24% are reported to have symptomatic seizures. Interestingly, epilepsy in 22q11 DS is more often associated with developmental delay and intellectual disability.…”

“…First, mouse models of 22q11.2DS have demonstrated erratic synaptic plasticity that subsequently resulted in abnormal neuronal excitation-inhibition. 6 Second, epilepsy in some patients is due to a structural brain lesion. Third, there are data suggesting that mutations in the Rab36 gene at position 22q11.2 may prevent neurotransmitter processing or release.…”