Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

Neurotherapeutics

Volumn 12, Issue 3, 2015, Pages 620-630

  Costales, Jesse L ^a   Kolevzon, Alexander ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

22q13 deletion syndrome; Autism; Autism spectrum disorder; Neurodevelopmental disorders; Phelan McDermid syndrome; SHANK3

Indexed keywords

ANKYRIN; RISPERIDONE; SCAFFOLD PROTEIN; SH3 AND MULTIPLE ANKYRIN REPEAT DOMAIN 3; TROFINETIDE; UNCLASSIFIED DRUG; NERVE PROTEIN; SHANK3 PROTEIN, HUMAN;

CHROMOSOME DELETION; CLINICAL FEATURE; DIFFERENTIAL DIAGNOSIS; HEART ATRIUM SEPTUM DEFECT; HUMAN; PHELAN MCDERMID SYNDROME; PRIORITY JOURNAL; REVIEW; ANIMAL; AUTISM SPECTRUM DISORDER; BRAIN; CHROMOSOME 22; CHROMOSOME DISORDERS; COMPLICATION; GENETICS; METABOLISM; MOUSE; NERVE CELL; SYNAPTIC TRANSMISSION;

ANIMALS; AUTISM SPECTRUM DISORDER; BRAIN; CHROMOSOME DELETION; CHROMOSOME DISORDERS; CHROMOSOMES, HUMAN, PAIR 22; HUMANS; MICE; NERVE TISSUE PROTEINS; NEURONS; SYNAPTIC TRANSMISSION;

EID: 84937633589     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-015-0352-z     Document Type: Review

References (111)

1. Watt JL, Olson IA, Johnston AW, Ross HS, Couzin DA, Stephen GS. A familial pericentric inversion of chromosome 22 with a recombinant subject illustrating a ‘pure’ partial monosomy syndrome. J Med Genet 1985;22:283–287.
2. Anderlid BM, Schoumans J, Anneren G, et al. FISH-mapping of a 100-kb terminal 22q13 deletion. Hum Genet 2002;110:439–443.
3. Dunham I, Shimizu N, Roe BA, et al. The DNA sequence of human chromosome 22. Nature 1999;402:489–495.
4. Florke S, Phi-van L, Muller-Esterl W, Scheuber HP, Engel W. Acrosin in the spermiohistogenesis of mammals. Differentiation 1983;24:250–256.
5. Kramer M, Backhaus O, Rosenstiel P, et al. Analysis of relative gene dosage and expression differences of the paralogs RABL2A and RABL2B by pyrosequencing. Gene 2010;455:1–7.
6. Boeckers TM, Winter C, Smalla KH, et al. Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Biochem Biophys Res Commun 1999;264:247–252.
7. Naisbitt S, Kim E, Tu JC, et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 1999;23:569–582.
8. Bonaglia MC, Giorda R, Borgatti R, et al. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated with the 22q13.3 deletion syndrome. Am J Hum Genet 2001;69:261–268.
9. Wilson HL, Wong AC, Shaw SR, et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 2003;40:575–584.
10. Soorya L, Kolevzon A, Zweifach J, et al. Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Mol Autism 2013;4:18.
11. Durand CM, Betancur C, Boeckers TM, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007;39:25–27.
12. Moessner R, Marshall CR, Sutcliffe JS, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 2007;81:1289–1297.
13. Gauthier J, Spiegelman D, Piton A, et al. Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet 2009;150B:421–424.
14. Boccuto L, Lauri M, Sarasua SM, et al. Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet 2013;21:310–316.
15. Aghajanian GK, Bloom FE. The formation of synaptic junctions in developing rat brain: a quantitative electron microscopic study. Brain Res 1967;6:716–727.
16. Uchino S, Wada H, Honda S, et al. Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem 2006;97:1203–1214.
17. Uchino S, Waga C. SHANK3 as an autism spectrum disorder-associated gene. Brain Dev 2013;35:106–110.
18. Bockers TM, Segger-Junius M, Iglauer P, et al. Differential expression and dendritic transcript localization of Shank family members: identification of a dendritic targeting element in the 3’ untranslated region of Shank1 mRNA. Mol Cell Neurosci 2004;26:182–190.
19. Raab M, Boeckers TM, Neuhuber WL. Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3)-scaffolding proteins are also present in postsynaptic specializations of the peripheral nervous system. Neuroscience 2010;171:421–433.
20. Ehlers MD. Synapse structure: glutamate receptors connected by the shanks. Curr Biol 1999;9:R848-R850.
21. Sheng M, Kim E. The Shank family of scaffold proteins. J Cell Sci 2000;113:1851–1856.
22. Gundelfinger ED, Boeckers TM, Baron MK, Bowie JU. A role for zinc in postsynaptic density asSAMbly and plasticity? Trends Biochem Sci 2006;31:366–373.
23. Kreienkamp HJ. Scaffolding proteins at the postsynaptic density: shank as the architectural framework. Handb Exp Pharmacol 2008:365–380.
24. Grabrucker AM, Schmeisser MJ, Schoen M, Boeckers TM. Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies. Trends Cell Biol 2011;21:594–603.
25. Bonaglia MC, Giorda R, Beri S, et al. Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. PLoS Genet 2011;7:e1002173.
26. Dhar SU, del Gaudio D, German JR, et al. 22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. Am J Med Genet A 2010;152A:573–581.
27. Gong X, Jiang YW, Zhang X, et al. High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PLoS One 2012;7:e34739.
28. Hamdan FF, Gauthier J, Araki Y, et al. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 2011;88:306–316.
29. Wang X, McCoy PA, Rodriguiz RM, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 2011;20:3093–3108.
30. Schmeisser MJ, Ey E, Wegener S, et al. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 2012;486:256–260.
31. Peca J, Feliciano C, Ting JT, et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011;472:437–442.
32. Roussignol G, Ango F, Romorini S, et al. Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J Neurosci 2005;25:3560–3570.
33. Tu JC, Xiao B, Naisbitt S, et al. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 1999;23:583–592.
34. Bozdagi O, Sakurai T, Papapetrou D, et al. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 2010;1:15.
35. Shcheglovitov A, Shcheglovitova O, Yazawa M, et al. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 2013;503:267–271.
36. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86:749–764.
37. Betancur C, Buxbaum JD. SHANK3 haploinsufficiency: a “common” but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol Autism 2013;4:17.
38. Leblond CS, Nava C, Polge A, et al. Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet 2014;10:e1004580.
39. Cooper GM, Coe BP, Girirajan S, et al. A copy number variation morbidity map of developmental delay. Nat Genet 2011;43:838–846.
40. Phelan MC. Deletion 22q13.3 syndrome. Orphanet J Rare Dis 2008;3:14.
41. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002;30:e57.
42. Peters DG, Yatsenko SA, Surti U, Rajkovic A. Recent advances of genomic testing in perinatal medicine. Semin Perinatol 2015;39:44–54.
43. Phelan K, McDermid HE. The 22q13.3 deletion syndrome (Phelan–McDermid syndrome). Mol Syndromol 2012;2:186–201.
44. Sykes NH, Toma C, Wilson N, et al. Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection. Eur J Hum Genet 2009;17:1347–1353.
45. Manning MA, Cassidy SB, Clericuzio C, et al. Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 2004;114:451–457.
46. Phelan MC, Rogers RC, Saul RA, et al. 22q13 deletion syndrome. Am J Med Genet 2001;101:91–99.
47. Lord C, Rutter M, Le Couteur 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;24:659–685.
48. Lord C, Risi S, Lambrecht L, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 2000;30:205–223.
49. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Revised Fourth Edition. American Psychiatric Association, Washington, DC, 2000.
50. Verhoeven WM, Egger JI, Willemsen MH, de Leijer GJ, Kleefstra T. Phelan–McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype? Neuropsychiatr Dis Treat 2012;8:175–179.
51. Kolevzon A, Angarita B, Bush L, et al. Phelan–McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. J Neurodev Disord 2014;6:39.
52. Cusmano-Ozog K, Manning MA, Hoyme HE. 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am J Med Genet C Semin Med Genet 2007;145C:393–398.
53. Prasad C, Prasad AN, Chodirker BN, et al. Genetic evaluation of pervasive developmental disorders: the terminal 22q13 deletion syndrome may represent a recognizable phenotype. Clin Genet 2000;57:103–109.
54. Sarasua SM, Boccuto L, Sharp JL, et al. Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet 2014;133:847–859.
55. Philippe A, Boddaert N, Vaivre-Douret L, et al. Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 2008;122:e376-e382.
56. Denayer A, Van Esch H, de Ravel T, et al. Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills. Mol Syndromol 2012;3:14–20.
57. Vucurovic K, Landais E, Delahaigue C, et al. Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion. Eur J Med Genet 2012;55:625–629.
58. Jeffries AR, Curran S, Elmslie F, et al. Molecular and phenotypic characterization of ring chromosome 22. Am J Med Genet A 2005;137:139–147.
59. Luciani JJ, de Mas P, Depetris D, et al. Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: cytogenetic, molecular, and clinical analyses of 32 new observations. J Med Genet 2003;40:690–696.
60. Nesslinger NJ, Gorski JL, Kurczynski TW, et al. Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet 1994;54:464–472.
61. Sarasua SM, Dwivedi A, Boccuto L, et al. 22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan–McDermid syndrome. Genet Med 2014;16:318–328.
62. Aldinger KA, Kogan J, Kimonis V, et al. Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A 2013;161A:131–136.
63. Phelan K, Betancur C. Clinical utility gene card for: deletion 22q13 syndrome. Eur J Hum Genet 2011;19.
64. Barakat AJ, Pearl PL, Acosta MT, Runkle BP. 22q13 deletion syndrome with central diabetes insipidus: a previously unreported association. Clin Dysmorphol 2004;13:191–194.
65. Rollins JD, Sarasua SM, Phelan K, DuPont BR, Rogers RC, Collins JS. Growth in Phelan–McDermid syndrome. Am J Med Genet A 2011;155A:2324–2326.
66. Koolen DA, Reardon W, Rosser EM, et al. Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation. Eur J Hum Genet 2005;13:1019–1024.
67. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res 2011;1380:42–77.
68. Sakai Y, Shaw CA, Dawson BC, et al. Protein interactome reveals converging molecular pathways among autism disorders. Sci Transl Med 2011;3:86ra49.
69. Darnell JC. Defects in translational regulation contributing to human cognitive and behavioral disease. Curr Opin Genet Dev 2011;21:465–473.
70. Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol 2009;19:231–234.
71. Hoeffer CA, Klann E. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 2010;33:67–75.
72. Darnell JC, Van Driesche SJ, Zhang C, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011;146:247–261.
73. Comery TA, Harris JB, Willems PJ, et al. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A 1997;94:5401–5404.
74. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23:185–188.
75. Meikle L, Talos DM, Onda H, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci 2007;27:5546–5558.
76. Zbuk KM, Eng C. Cancer phenomics: RET and PTEN as illustrative models. Nat Rev Cancer 2007;7:35–45.
77. Schmidt H, Kern W, Giese R, Hallschmid M, Enders A. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial. J Med Genet 2009;46:217–222.
78. Reger DL, Foley EA, Watson RP, et al. Monofluoride bridged, binuclear metallacycles of first row transition metals supported by third generation bis(1-pyrazolyl)methane ligands: unusual magnetic properties. Inorg Chem 2009;48:10658–10669.
79. Van den Heuvel ER, Zwanenburg RJ, Van Ravenswaaij-Arts CM. A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan–McDermid syndrome: A comparison of different designs. Stat Methods Med Res 2014 Nov 19 [Epub ahead of print].
80. Pasini A, D’Agati E, Casarelli L, Curatolo P. Dose-dependent effect of risperidone treatment in a case of 22q13.3 deletion syndrome. Brain Dev 2010;32:425–427.
81. Guy M. ECDEU Assessment manual for psychopharmacology. US Department of Health, and Welfare, Washington, DC, Publication ADM, 1976, pp. 534–537.
82. Choi YK, Gardner MP, Tarazi FI. Effects of risperidone on glutamate receptor subtypes in developing rat brain. Eur Neuropsychopharmacol 2009;19:77–84.
83. D’Mello SR, Borodezt K, Soltoff SP. Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways: possible involvement of PI 3-kinase in IGF-1 signaling. J Neurosci 1997;17:1548–1560.
84. Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993;75:73–82.
85. Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993;75:59–72.
86. Bozdagi O, Tavassoli T, Buxbaum JD. Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol Autism 2013;4:9.
87. Rosenbloom AL. The role of recombinant insulin-like growth factor I in the treatment of the short child. Curr Opin Pediatr 2007;19:458–464.
88. Ravnan JB, Tepperberg JH, Papenhausen P, et al. Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet 2006;43:478–489.
89. Abraham WC, Bear MF. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci 1996;19:126–130.
90. Kolevzon A. A pilot treatment study of insulin-like growth factor-1 (IGF-1) in autism spectrum disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT01970345?term=NCT01970345. Accessed September, 2014.
91. Khwaja OS, Ho E, Barnes KV, et al. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A 2014;111:4596–4601.
92. Mount RH, Charman T, Hastings RP, Reilly S, Cass H. The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. J Child Psychol Psychiatry 2002;43:1099–1110.
93. Esbensen AJ, Rojahn J, Aman MG, Ruedrich S. Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. J Autism Dev Disord 2003;33:617–629.
94. Sara VR, Carlsson-Skwirut C, Drakenberg K, et al. The biological role of truncated insulin-like growth factor-1 and the tripeptide GPE in the central nervous system. Ann N Y Acad Sci 1993;692:183–191.
95. Guan J, Waldvogel HJ, Faull RL, Gluckman PD, Williams CE. The effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate in different regions following hypoxic-ischemic brain injury in adult rats. Neuroscience 1999;89:649–659.
96. Corvin AP, Molinos I, Little G, et al. Insulin-like growth factor 1 (IGF1) and its active peptide (1–3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms. Neurosci Lett 2012;520:51–56.
97. Guan J, Thomas GB, Lin H, et al. Neuroprotective effects of the N-terminal tripeptide of insulin-like growth factor-1, glycine-proline-glutamate (GPE) following intravenous infusion in hypoxic-ischemic adult rats. Neuropharmacology 2004;47:892–903.
98. Wei HH, Lu XC, Shear DA, et al. NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats. J Neuroinflammation 2009;6:19.
99. Treagus R. Neuren’s NNZ-2566 successful in demonstrating clinical benefit in Rett syndrome Phase 2 trial. In: Neurin (NEU) ASX Announcement [online]. Available at: http://www.neurenpharma.com/IRM/Company/ShowPage.aspx/PDFs/1448-10000000/NeurensuccessfulinRettsyndromePhase2trial. Accessed January 4, 2015.
100. FitzGerald PM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord 1990;5:195–202.
101. Payakachat N, Tilford JM, Kovacs E, Kuhlthau K. Autism spectrum disorders: a review of measures for clinical, health services and cost-effectiveness applications. Expert Rev Pharmacoecon Outcomes Res 2012;12:485–503.
102. International Human Genome Sequencing C. Finishing the euchromatic sequence of the human genome. Nature 2004;431:931–945.
103. Lim S, Naisbitt S, Yoon J, et al. Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development. J Biol Chem 1999;274:29510–29518.
104. Bockers TM, Mameza MG, Kreutz MR, et al. Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alpha-fodrin. J Biol Chem 2001;276:40104–40112.
105. Wyszynski M, Kim E, Dunah AW, et al. Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron 2002;34:39–52.
106. Lu W, Ziff EB. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 2005;47:407–421.
107. Sala C, Piech V, Wilson NR, Passafaro M, Liu G, Sheng M. Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 2001;31:115–130.
108. Hayashi MK, Tang C, Verpelli C, et al. The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell 2009;137:159–171.
109. Baron MK, Boeckers TM, Vaida B, et al. An architectural framework that may lie at the core of the postsynaptic density. Science 2006;311:531–535.
110. Boeckers TM, Liedtke T, Spilker C, et al. C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3. J Neurochem 2005;92:519–524.
111. Phelan K, Rogers RC. Phelan–McDermid Syndrome. 2005 May 11 [updated 2011 Aug 25]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1198/. Accessed March 26, 2015.