Prospective longitudinal overnight video-EEG evaluation in Phelan–McDermid Syndrome

Khan, Omar; Zhou, Xiangping; Leon, Jill; Kessler, Riley; Gaughan, Thomas; D’Souza, Precilla; Gropman, Andrea; Cohen, Ninette; Rennert, Owen M.; Buckley, Ashura; Inati, Sara K.; Thurm, Audrey

doi:10.1016/j.yebeh.2017.11.034

Cited by 15 publications

(23 citation statements)

References 35 publications

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“…Epilepsy is reported in 17% to 70% of individuals with PMS [9,[11][12][13][14]. As individuals with PMS age, they appear to be at increased risk for bipolar disorder [15][16][17][18][19][20] and an associated risk of significant cognitive and behavioral regression [5,6,16,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Kohlenberg

Trelles

McLarney

et al. 2020

J Neurodevelop Disord

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Background: Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. Methods: Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. Results: The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. Conclusions: This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS.

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Section: Introductionmentioning

confidence: 99%

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Kohlenberg

Trelles

McLarney

et al. 2020

J Neurodevelop Disord

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“…Electroencephalography (EEG) offers particular opportunity in this regard, because it can measure network dynamics in both humans and animal models, allowing for both forward and back-translation of findings. Clinical EEG (evaluated by visual review) frequently demonstrates abnormalities in PMS, including generalized slowing of activity, slowing or absence of the occipital dominant rhythm, and epileptiform activity [ 5 , 16 ]. Epileptiform activity on EEG is also frequently seen in ASD more broadly [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome

et al. 2021

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Background Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. Methods Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. Results We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). Conclusions Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials.

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“…Concerning epilepsy, there are inconsistent data that reveal prevalent seizures and EEG pathology in cases of regression [2]. In contrast, there are also investigations of prolonged awake and asleep states using video-EEG with various EEG abnormalities but without clinical signs of regression during a follow-up period over one year [7].…”

Section: Discussionmentioning

confidence: 99%

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

Jesse

Delling

Schön

et al. 2021

IJMS

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Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone.

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Prospective longitudinal overnight video-EEG evaluation in Phelan–McDermid Syndrome

Cited by 15 publications

References 35 publications

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome

Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

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