Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion

Vucurovic, Ksenija; Landais, Emilie; Delahaigue, Cécile; Eutrope, Julien; Schneider, Anouck; Leroy, Camille; Kabbaj, Hamza; Motté, Jacques; Gaillard, Dominique; Rolland, Aurélia; Doco‐Fenzy, Martine

doi:10.1016/j.ejmg.2012.07.009

Cited by 46 publications

(38 citation statements)

References 15 publications

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“…Significant regression in motor and social skills has also been reported among patients in our sample and in the literature [2,5,30,57,58]. Isolated reports have emerged recently describing significant medical complications of SHANK3 deficiency in the context of severe cognitive and behavioral regression, including seizure-induced aspiration [2], renal failure [5] and pneumonia [58].…”

Section: Discussionsupporting

confidence: 54%

“…Isolated reports have emerged recently describing significant medical complications of SHANK3 deficiency in the context of severe cognitive and behavioral regression, including seizure-induced aspiration [2], renal failure [5] and pneumonia [58]. In addition, recent reports of psychiatric comorbidity in individuals with SHANK3 deficiency suggest that, as patients age, they may be at increased risk for bipolar disorder [30,57,59]. Our results suggest that regression may occur at various ages, across multiple domains, and is often associated with the onset of seizures.…”

Section: Discussionmentioning

confidence: 99%

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Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

et al. 2013

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Background22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal of providing a comprehensive picture of the medical and behavioral profile of the syndrome.MethodsA serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G.ResultsThirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features.ConclusionsThis study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the prominence of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

et al. 2013

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“…Altered expression or function of this scaffolding protein, and others of the same family, are linked to several human synaptopathies, including schizophrenia and BD (Guilmatre et al, 2014). Case studies have provided further support for a link between SHANK3 dysfunction and BD (Vucurovic et al, 2012). The SHANK family of proteins is crucial for synapse formation, maintenance, and modulation of excitatory and inhibitory balance (Sudhof and Malenka, 2008).…”

Section: Genetic Models Of Bipolar Maniamentioning

confidence: 97%

Animal models of bipolar mania: The past, present and future

2016

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Bipolar disorder (BD) is the sixth leading cause of disability in the world according to the World Health Organization and affects nearly 6 million (~2.5% of the population) adults in the United State alone each year. BD is primarily characterized by mood cycling of depressive (e.g., helplessness, reduced energy and activity, and anhedonia) and manic (e.g., increased energy and hyperactivity, reduced need for sleep, impulsivity, reduced anxiety and depression), episodes. The following review describes several animal models of bipolar mania with a focus on more recent findings using genetically modified mice, including several with the potential of investigating the mechanisms underlying ‘mood’ cycling (or behavioral switching in rodents). We discuss whether each of these models satisfy criteria of validity (i.e., face, predictive, and construct), while highlighting their strengths and limitations. Animal models are helping to address critical questions related to pathophysiology of bipolar mania, in an effort to more clearly define necessary targets of first-line medications, lithium and valproic acid, and to discover novel mechanisms with the hope of developing more effective therapeutics. Future studies will leverage new technologies and strategies for integrating animal and human data to reveal important insights into the etiology, pathophysiology, and treatment of BD.

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“…Most patients with PMS have limited means of communication and cannot follow more than simple commands. Some reports have also described a regression in motor, language, and behavioral skills in the context of seizure onset or exacerbation and structural brain abnormalities [10,11,50,[55][56][57].…”

Section: Medical Featuresmentioning

confidence: 99%