Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: An overview and case series

Butcher, Nancy J.; Boot, Erik; Lang, Anthony E.; Andrade, Danielle M.; Vorstman, Jacob; McDonald‐McGinn, Donna M.; Bassett, Anne S.

doi:10.1002/ajmg.a.38708

Cited by 29 publications

(24 citation statements)

References 105 publications

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“…Recognition and treatment of both stuporous and hypermotoric catatonia is crucial, as symptoms can lead to life-threatening complications. Other genetic conditions involving copy number variants, such as 22q11.2 deletions [36], have also been associated with psychiatric symptoms and with catatonia. Similar to their use in treating catatonia in other conditions, benzodiazepines and ECT were used in this cohort with reported tolerability and effectiveness.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…78 In addition, 22q11.2 deletion syndrome, which features thymic aplasia and a resultant absence of peripheral T cells, 79 has also been linked to catatonia. 80 Whether this association is due to immunodeficiency, the high rates of various autoimmune disorders present in the syndrome, or to another cause remains unclear.…”

Section: Autoimmune Disorders Causing Catatoniamentioning

confidence: 99%

Catatonia and the immune system: a review

Rogers

Pollak

Blackman

et al. 2019

The Lancet Psychiatry

146

119

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Catatonia is a psychomotor disorder featuring stupor, posturing, and echophenomena. This Series paper examines the evidence for immune dysregulation in catatonia. Activation of the innate immune system is associated with mutism, withdrawal, and psychomotor retardation, which constitute the neurovegetative features of catatonia. Evidence is sparse and conflicting for acute-phase activation in catatonia, and whether this feature is secondary to immobility is unclear. Various viral, bacterial, and parasitic infections have been associated with catatonia, but it is primarily linked to CNS infections. The most common cause of autoimmune catatonia is N-methyl-D-aspartate receptor (NMDAR) encephalitis, which can account for the full spectrum of catatonic features. Autoimmunity appears to cause catatonia less by systemic inflammation than by the downstream effects of specific actions on extracellular antigens. The specific association with NMDAR encephalitis supports a hypothesis of glutamatergic hypofunction in catatonia.

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“…The hallmark symptoms of PD are present in 22q11.2DS‐associated PD . However, PD in 22q11.2DS may be difficult to diagnose as a result of the clinically complex multisystem nature of the condition with lack of familiarity with the syndrome, even compared to rarer conditions . For example, Wilson's disease was considered, but not confirmed, in at least 4 reported patients with 22q11.2DS and abnormal movements .…”

Section: Diagnostic Challengesmentioning

confidence: 99%

“…10 Additional genetic and environmental factors that contribute to the increased PD risk in this group of patients are yet to be determined. A whole-genome sequencing pilot study in patients with 22q11.2DS showed nominal enrichment in the PD cases of 9,10 To be determined Other movement disorders (e.g., myoclonic disorders) 9,[11][12][13] To be determined Functional neurological disorder 6 To be determined Psychiatric Attention deficit and hyperactivity disorder (pediatric history) 8 >30% Anxiety disorders 8,17 30% Schizophrenia 8,17 20% to 25% Cognitive a Learning disabilities 5 >90% Intellectual disabilities 5 35% Cognitive deterioration 14 To be determined Sensory system…”

Section: Microdeletion 22q112: a Genetic Risk Factor For Pdmentioning

confidence: 99%

“…23 However, PD in 22q11.2DS may be difficult to diagnose as a result of the clinically complex multisystem nature of the condition with lack of familiarity with the syndrome, even compared to rarer conditions. 6 For example, Wilson's disease was considered, but not confirmed, in at least 4 reported patients with 22q11.2DS and abnormal movements. [28][29][30][31] Use of antipsychotic medications may delay the diagnosis of PD significantly, given that parkinsonism may be assumed to be drug induced.…”

Section: Diagnostic Challengesmentioning

confidence: 99%

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22q11.2 Deletion Syndrome–Associated Parkinson's Disease

Boot

Bassett

Marras

2018

Movement Disord Clin Pract

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Background22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition associated with an increased risk of early‐onset Parkinson's disease (PD).MethodsWe review the clinical, neuroimaging, and neuropathological observations, as well as diagnostic challenges, of PD in 22q11.2DS. We conducted a search of PubMed up until June 1, 2018 and personal files to identify relevant publications.Results22q11.2DS‐associated PD is responsible for approximately 0.5% of early‐onset PD. The hallmark motor symptoms and neuropathology of PD, and typical findings of reduced striatal dopamine transporter binding with molecular imaging, are present in 22q11.2DS‐associated PD. Mean age at PD onset in 22q11.2DS is relatively young (∼40 years). Patients with 22q11.2DS‐associated PD show a good response to levodopa.ConclusionsFurther recognition of 22q11.2DS and study of PD in people with 22q11.2DS could provide insights into the mechanisms that cause PD in the general population. 22q11.2DS may serve as an identifiable PD model to study prodromal PD and disease‐modifying treatments.

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Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: An overview and case series

Cited by 29 publications

References 105 publications

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Catatonia and the immune system: a review

22q11.2 Deletion Syndrome–Associated Parkinson's Disease

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