Myoclonic epilepsy, parkinsonism, schizophrenia and left-handedness as common neuropsychiatric features in 22q11.2 deletion syndrome

Abstract

Background22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations.MethodsWe enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG).ResultsThirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics.Conclusions22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients’ genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.

Age‐Related Parkinsonian Signs in Microdeletion 22q11.2

“…18 The findings are also consistent with those for other patient groups at increased risk of PD 19,20 and previous smaller studies of 22q11.2DS and healthy controls. [5][6][7] Furthermore, the results indicate that vigilance for parkinsonian signs should not be restricted to adults with 22q11.2DS who take antipsychotic medication. [5][6][7]21 When we altered the MDS-UPDRS total score for a statistical outlier to just one unit larger than the next highest score to prevent an overproportional effect on the regression model, the values for psychotic illness changed to B = 3.31, SE B = 1.36, β = 0.24, t = 2.44, and P = 0.02.…”

“…4 Also, there is some evidence that nondegenerative parkinsonian signs, including medication-induced parkinsonism, may be common in 22q11.2DS at a relatively young age. [5][6][7] In this study, we examined the presence and severity of parkinsonian motor signs in adults with 22q11.2DS, and demographic and clinical factors possibly associated with these signs, in comparison to healthy controls. We used the International Parkinson and Movement Disorder Society-sponsored revision of the UPDRS (MDS-UPDRS), 8 and three-dimensional (3D) motion-tracking technology to address the likelihood of low bradykinesia scores with limited variability that may be expected in a young population.…”

Clozapine‐induced gastroesophageal rumination in 22q11.2 Deletion Syndrome. A case report on gastroesophageal side effects management without renouncing clozapine's effectiveness

“…4,5 Psychosis in 22q11.2DS is treated in the same way as idiopathic schizophrenia, and clozapine results the most effective tool in pharmacological treatment of treatment-resistant schizophrenia (TRS) in 22q11.2DS even if entailing more severe side effects, as seizures, hematological problems, and myocarditis, compared to individuals with nongenetic determined psychotic disorders. [6][7][8] The correlation between the employment of clozapine and the onset or worsening of obsessive-compulsive symptoms has been deeply investigated in literature. 9,10 The present work is aimed to further describe the set of side effects associated with the employment of clozapine in people with 22q11.2DS and schizophrenia.…”

“…22q11DS is associated with an incidence of 25%‐33% of psychotic disorders in lifespan 3 sharing the same clinical characteristics with idiopathic psychosis in regard to premorbid conditions, age of onset, and symptoms 4,5 . Psychosis in 22q11.2DS is treated in the same way as idiopathic schizophrenia, and clozapine results the most effective tool in pharmacological treatment of treatment‐resistant schizophrenia (TRS) in 22q11.2DS even if entailing more severe side effects, as seizures, hematological problems, and myocarditis, compared to individuals with nongenetic determined psychotic disorders 6‐8 . The correlation between the employment of clozapine and the onset or worsening of obsessive‐compulsive symptoms has been deeply investigated in literature 9,10 .…”

Síndrome de Janz: Reporte de un Caso Clínico en Ecuador

“…A nivel de América Latina se ha encontrado que la mutación de la mioclonina ( EFHC1 ) "relacionado con EMJ" se ha encontrado en el 9-20% de las familias México -Americanas, pero solo en el 3% de las familias japonesas con este trastorno, esto podría orientar hacia un componente de raza y etnias en donde la Epilepsia Mioclónica Juvenil es más frecuente dentro de la población americana (6). Genéticamente, la EMJ tiene una herencia poligénica o monogénica autosómica dominante, hasta el momento se han relacionado 29 loci cromosómicos y se han identificado variaciones en varios genes (CACNB4, CASR, GABRA1, GABRD, CLCN2, SLC2A1 y EFHC1), además de microdeleciones cromosómicas en 15q13.3, 15q11.2 y 16p13.11 que se asocian a EMJ, la región 22q11.22 también se ha relacionado con alteraciones neurológicas y neuropsiquiátricas, que van desde la epilepsia hasta la esquizofrenia las mismas que comparten alteraciones de la conducta, déficit de atención, hiperactividad (7) (8) . Sin embargo, la mayoría de pacientes con epilepsia mioclónica juvenil tienen mutaciones en EFHC1 la misma que codifica una proteína que participa en la corticogénesis durante el desarrollo cerebral (9).…”