Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

BMC Psychiatry

Laurence Robel⁵  Jean-Paul Bonnefont⁶  Valérie Malan³  Nathalie Boddaert⁷  Nadia Bahi-Buisson²  Marlène Rio¹  Yann Craus⁴  Anne Philippe¹ 

[1] Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, UMR1163, Paris, France;Pediatric Neurology, APHP Hôpital Necker Enfants Malades, Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Paris, France;Department of Cytogenetic, APHP Hôpital Necker Enfants Malades, Paris, France;Department of Child and Adolescent Psychiatry, APHP Hôpital Necker Enfants Malades, Paris, France;APHP Hôpital Necker Enfants Malades, Paris, France;Molecular Genetics Unit, APHP Hôpital Necker Enfants Malades, Paris, France;Department of Imagery, APHP Hôpital Necker Enfants Malades, Paris, France

关键词: Regression;    Heller syndrome;    Childhood disintegrative disorder (CDD);    ASD;    Autism;    22q13.3 deletion syndrome;    SHANK3;   

Others  :  1231590
DOI  :  10.1186/s12888-015-0631-6

 received in 2015-07-14, accepted in 2015-10-02,  发布年份 2015

【 摘 要 】

Background

Deletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).

Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.

Case presentation

Here, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.

The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.

Conclusion

Our present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.

【 授权许可】

   
2015 Philippe et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, et al.: Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007, 39(1):25-7.
• [2]Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, et al.: Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 2007, 81(6):1289-97.
• [3]Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, et al.: Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet 2014., 10(9) Article ID e1004580
• [4]Boccuto L, Lauri M, Sarasua SM, Skinner CD, Buccella D, Dwivedi A, et al.: Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet 2013, 21(3):310-6.
• [5]Gauthier J, Champagne N, Lafrenière RG, Xiong L, Spiegelman D, Brustein E, et al.: De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc Natl Acad Sci U S A 2010, 107(17):7863-8.
• [6]Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, et al.: Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 2011, 88(3):306-16.
• [7]Lesca G, Rudolf G, Labalme A, Hirsch E, Arzimanoglou A, Genton P, et al.: Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism. Epilepsia 2012, 53(9):1526-38.
• [8]Jiang Y-H, Ehlers MD: Modeling autism by SHANK mutations in mice. Neuron 2013, 78(1):8-27.
• [9]Bonaglia MC, Giorda R, Beri S, De Agostini C, Novara F, Fichera M, et al.: Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. PLoS Genet 2011., 7(7) Article ID e1002173
• [10]Figura MG, Coppola A, Bottitta M, Calabrese G, Grillo L, Luciano D, et al.: Seizures and EEG pattern in the 22q13.3 deletion syndrome: clinical report of six italian cases. Seizure 2014, 23(9):774-9.
• [11]Nemirovsky SI, Córdoba M, Zaiat JJ, Completa SP, Vega PA, González-Morón D, et al.: Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder. Plos One 2015., 10(2) Article ID e0116358
• [12]Hara M, Ohba C, Yamashita Y, Saitsu H, Matsumoto N, Matsuishi T: De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient. Am J Med Genet A 2015, 167(7):1593-6.
• [13]Kolevzon A, Cai G, Soorya L, Takahashi N, Grodberg D, Kajiwara Y, et al.: Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities. Brain Res 2011, 1380:98-105.
• [14]Quintáns B, Ordóñez-Ugalde A, Cacheiro P, Carracedo A, Sobrido MJ: Medical genomics: the intricate path from genetic variant identification to clinical interpretation. Appl Transl Genomics 2014, 3:60-7.
• [15]Vucurovic K, Landais E, Delahaigue C, Eutrope J, Schneider A, Leroy C, et al.: Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion. Eur J Med Genet 2012, 55(11):625-9.
• [16]Serret S, Thümmler S, Dor E, Vesperini S, Santos A, Askenazy F: Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports. BMC Psychiatry 2015, 7(15):107. BioMed Central Full Text
• [17]Denayer A, Van Esch H, de Ravel T, Frijns JP, Van Buggenhout G, Vogels A, et al.: Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills. Mol Syndromol 2012, 3(1):14-20.
• [18]Verhoeven WM, Egger JI, Cohen-Snuijf R, Kant SG, de Leeuw N: Phelan-McDermid syndrome: clinical report of a 70-year-old woman. Am J Med Genet A 2013, 161A(1):158-61.
• [19]Lord C, Rutter M, LeCouteur A: Autism diagnostic interview-revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994, 24:659-85.
• [20]Schopler E, Reichler RJ, De Vellis RF, Daly K: Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 1980, 10(1):91-103.
• [21]Schopler E, Reichler RJ, Bashford A, Lansing MD, Marcus L: Psychoeducational profile revised (PEP-R). Pro-Ed., Austin, TX; 1990.
• [22]Lézine I, Brunet O: Presentation of a French scale of tests for infants. Ann Med Psychol 1950, 108(14):499.
• [23]Vaivre-Douret L: Batterie d’Evaluations des Fonctions Neuro-Motrices de l’enfant (NP-MOT). Edition du Centre de Psychologie Appliquée, Paris (France); 2006.
• [24]Heller T: Dementia infantilis. Zeitschrift für die Erfoschung und Behandlung des Jugendlichen Schwachsinns. 1908.
• [25]Westphal A, Schelinski S, Volkmar F, Pelphrey K: Revisiting regression in autism: Heller’s dementia infantilis. Includes a translation of über dementia infantilis. J Autism Dev Disord 2013, 43(2):265-71.
• [26]Fombonne E: Prevalence of childhood disintegrative disorder. Autism: Int J Res Pract 2002, 6(2):149-57.
• [27]Malhotra S, Subodh BN, Parakh P, Lahariya S: Brief report: childhood disintegrative disorder as a likely manifestation of vitamin B12 deficiency. J Autism Dev Disord 2013, 43(9):2207-10.
• [28]Creten C, Van der Zwaan S, Blankespoor RJ, Maatkamp A, Nicolai J, van Os J, et al.: Late onset autism and anti-NMDA-receptor encephalitis. Lancet 2011, 378(9785):98.
• [29]Rossignol G, Ango F, Romorini S, Tu JC, Sala C, Worley PF, et al.: Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J Neurosci 2005, 25(14):3560-70.
• [30]Philippe A, Boddaert N, Vaivre-Douret L, Robel L, Danon-Boileau L, Malan V, et al.: Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 2008, 122(2):376-82.
• [31]Cochoy DM, Kolevzon A, Kajiwara Y, Schoen M, Pascual-Lucas M, Lurie S, et al.: Phenotypic and functional analysis of SHANK3 stop mutations identified in individuals with ASD and/or ID. Mol Autism 2015, 6:23. BioMed Central Full Text
• [32]Anderlid BM, Schoumans J, Annerén G, Tapia-Paez I, Dumanski J, Blennow E, et al.: FISH-mapping of a 100-Kb terminal 22q13 deletion. Hum Genet 2002, 110(5):439-43.