Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring

详细信息    查看全文

• 作者：Alexander Kolevzon (1) (10) (11) (2) (3)
  Benjamin Angarita (1) (2)
  Lauren Bush (1) (2)
  A Ting Wang (1) (10) (2) (4)
  Yitzchak Frank (1) (2) (3) (5)
  Amy Yang (6)
  Robert Rapaport (3) (7)
  Jeffrey Saland (3)
  Shubhika Srivastava (3) (8)
  Cristina Farrell (1) (3) (9)
  Lisa J Edelmann (6)
  Joseph D Buxbaum (1) (10) (11) (2) (4) (6)
  
  1. Seaver Autism Center for Research and Treatment ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  10. Friedman Brain Institute ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  11. Mindich Child Health and Development Institute ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  2. Department of Psychiatry ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  3. Department of Pediatrics ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  4. Department of Neuroscience ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  5. Department of Neurology ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  6. Department of Genetics and Genomic Sciences ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  7. Division of Endocrinology and Diabetes ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  8. Department of Cardiology ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  9. Division of Behavioral Pediatrics ; Icahn School of Medicine at Mount Sinai ; One Gustave L. Levy Place ; New York ; NY ; 10029 ; USA
  
• 关键词：Phelan ; McDermid syndrome ; 22q13 deletion syndrome ; SHANK3 ; Autism ; Autism spectrum disorder ; Neurodevelopmental disorders ; Practice parameters
• 刊名：Journal of Neurodevelopmental Disorders
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：6
• 期：1
• 全文大小：1,782 KB
• 参考文献：1. Leblond, CS, Nava, C, Polge, A, Gauthier, J, Huguet, G, Lumbroso, S, Giuliano, F, Stordeur, C, Depienne, C, Mouzat, K, Pinto, D, Howe, J, Lemi猫re, N, Durand, CM, Guibert, J, Ey, E, Toro, R, Peyre, H, Mathieu, A, Amsellem, F, Rastam, M, Gillberg, IC, Rappold, GA, Holt, R, Monaco, AP, Maestrini, E, Galan, P, Heron, D, Jacquette, A, Afenjar, A (2014) Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments. PLoS Genet 10: pp. e1004580 CrossRef
  2. Durand, CM, Betancur, C, Boeckers, TM, Bockmann, J, Chaste, P, Fauchereau, F, Nygren, G, Rastam, M, Gillberg, IC, Anckars盲ter, H, Sponheim, E, Goubran-Botros, H, Delorme, R, Chabane, N, Mouren-Simeoni, MC, de Mas, P, Bieth, E, Rog茅, B, H茅ron, D, Burglen, L, Gillberg, C, Leboyer, M, Bourgeron, T (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39: pp. 25-27 CrossRef
  3. Gauthier, J, Spiegelman, D, Piton, A, Lafreni猫re, RG, Laurent, S, St-Onge, J, Lapointe, L, Hamdan, FF, Cossette, P, Mottron, L, Fombonne, E, Joober, R, Marineau, C, Drapeau, P, Rouleau, GA (2009) Novel de novo SHANK3 mutation in autistic patients. Am J Med Genet B Neuropsychiatr Genet 150B: pp. 421-424 CrossRef
  4. Moessner, R, Marshall, CR, Sutcliffe, JS, Skaug, J, Pinto, D, Vincent, J, Zwaigenbaum, L, Fernandez, B, Roberts, W, Szatmari, P, Scherer, SW (2007) Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 81: pp. 1289-1297 CrossRef
  5. Pinto, D, Delaby, E, Merico, D, Barbosa, M, Merikangas, A, Klei, L, Thiruvahindrapuram, B, Xu, X, Ziman, R, Wang, Z, Vorstman, JA, Thompson, A, Regan, R, Pilorge, M, Pellecchia, G, Pagnamenta, AT, Oliveira, B, Marshall, CR, Magalhaes, TR, Lowe, JK, Howe, JL, Griswold, AJ, Gilbert, J, Duketis, E, Dombroski, BA, De Jonge, MV, Cuccaro, M, Crawford, EL, Correia, CT, Conroy, J (2014) Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet 94: pp. 677-694 CrossRef
  6. Cooper, GM, Coe, BP, Girirajan, S, Rosenfeld, JA, Vu, TH, Baker, C, Williams, C, Stalker, H, Hamid, R, Hannig, V, Abdel-Hamid, H, Bader, P, McCracken, E, Niyazov, D, Leppig, K, Thiese, H, Hummel, M, Alexander, N, Gorski, J, Kussmann, J, Shashi, V, Johnson, K, Rehder, C, Ballif, BC, Shaffer, LG, Eichler, EE (2011) A copy number variation morbidity map of developmental delay. Nat Genet 43: pp. 838-846 CrossRef
  7. Gong, X, Jiang, YW, Zhang, X, An, Y, Zhang, J, Wu, Y, Wang, J, Sun, Y, Liu, Y, Gao, X, Shen, Y, Wu, X, Qiu, Z, Jin, L, Wu, BL, Wang, H (2012) High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PLoS One 7: pp. e34739 CrossRef
  8. Bonaglia, MC, Giorda, R, Mani, E, Aceti, G, Anderlid, BM, Baroncini, A, Pramparo, T, Zuffardi, O (2006) Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J Med Genet 43: pp. 822-828 CrossRef
  9. Boeckers, TM (2006) The postsynaptic density. Cell Tissue Res 326: pp. 409-422 CrossRef
  10. Darnell, JC (2011) Defects in translational regulation contributing to human cognitive and behavioral disease. Curr Opin Genet Dev 21: pp. 465-473 CrossRef
  11. Sakai, Y, Shaw, CA, Dawson, BC, Dugas, DV, Al-Mohtaseb, Z, Hill, DE, Zoghbi, HY (2011) Protein interactome reveals converging molecular pathways among autism disorders. Sci Transl Med 3: pp. 86ra49
  12. Bozdagi, O, Sakurai, T, Papapetrou, D, Wang, X, Dickstein, DL, Takahashi, N, Kajiwara, Y, Yang, M, Katz, AM, Scattoni, ML, Harris, MJ, Saxena, R, Silverman, JL, Crawley, JN, Zhou, Q, Hof, PR, Buxbaum, JD (2010) Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 1: pp. 15 CrossRef
  13. Kouser, M, Speed, HE, Dewey, CM, Reimers, JM, Widman, AJ, Gupta, N, Liu, S, Jaramillo, TC, Bangash, M, Xiao, B, Worley, PF, Powell, CM (2013) Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission. J Neurosci 33: pp. 18448-18468 CrossRef
  14. Pe莽a, J, Feliciano, C, Ting, JT, Wang, W, Wells, MF, Venkatraman, TN, Lascola, CD, Fu, Z, Feng, G (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472: pp. 437-442 CrossRef
  15. Raynaud, F, Janossy, A, Dahl, J, Bertaso, F, Perroy, J, Varrault, A, Vidal, M, Worley, PF, Boeckers, TM, Bockaert, J, Marin, P, Fagni, L, Homburger, V (2013) Shank3-rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. J Neurosci 33: pp. 9699-9715 CrossRef
  16. Wang, X, McCoy, PA, Rodriguiz, RM, Pan, Y, Je, HS, Roberts, AC, Kim, CJ, Berrios, J, Colvin, JS, Bousquet-Moore, D, Lorenzo, I, Wu, G, Weinberg, RJ, Ehlers, MD, Philpot, BD, Beaudet, AL, Wetsel, WC, Jiang, YH (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 20: pp. 3093-3108 CrossRef
  17. Yang, M, Bozdagi, O, Scattoni, ML, W枚hr, M, Roullet, FI, Katz, AM, Abrams, DN, Kalikhman, D, Simon, H, Woldeyohannes, L, Zhang, JY, Harris, MJ, Saxena, R, Silverman, JL, Buxbaum, JD, Crawley, JN (2012) Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci 32: pp. 6525-6541 CrossRef
  18. Bozdagi, O, Tavassoli, T, Buxbaum, JD (2013) Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol Autism 4: pp. 9 CrossRef
  19. Shcheglovitov, A, Shcheglovitova, O, Yazawa, M, Portmann, T, Shu, R, Sebastiano, V, Krawisz, A, Froehlich, W, Bernstein, JA, Hallmayer, JF, Dolmetsch, RE (2013) SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503: pp. 267-271
  20. Manning, M, Hudgins, L (2010) Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med 12: pp. 742-745 CrossRef
  21. Miller, DT, Adam, MP, Aradhya, S, Biesecker, LG, Brothman, AR, Carter, NP, Church, DM, Crolla, JA, Eichler, EE, Epstein, CJ, Faucett, WA, Feuk, L, Friedman, JM, Hamosh, A, Jackson, L, Kaminsky, EB, Kok, K, Krantz, ID, Kuhn, RM, Lee, C, Ostell, JM, Rosenberg, C, Scherer, SW, Spinner, NB, Stavropoulos, DJ, Tepperberg, JH, Thorland, EC, Vermeesch, JR, Waggoner, DJ, Watson, MS (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86: pp. 749-764 CrossRef
  22. Schaefer, GB, Mendelsohn, NJ (2008) Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med 10: pp. 301-305 CrossRef
  23. Schaefer, GB, Mendelsohn, NJ (2013) Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med 15: pp. 399-407 CrossRef
  24. Phelan K, Betancur C: Clinical utility gene card for: deletion 22q13 syndrome. / Eur J Hum Genet 2011.,19(4): doi:10.1038/ejhg.2010.193. Epub 2010 Dec 8
  25. Phelan, K, McDermid, HE (2012) The 22q13.3 deletion syndrome (Phelan-McDermid syndrome). Mol Syndromol 2: pp. 186-201
  26. Phelan, MC (2008) Deletion 22q13.3 syndrome. Orphanet J Rare Dis 3: pp. 14 CrossRef
  27. Phelan, MC, Rogers, RC, Saul, RA, Stapleton, GA, Sweet, K, McDermid, H, Shaw, SR, Claytor, J, Willis, J, Kelly, DP (2001) 22q13 deletion syndrome. Am J Med Genet 101: pp. 91-99 CrossRef
  28. Phelan, K, Rogers, C (2011) Phelan-McDermid Syndrome, Gene Reviews [Internet]. University of Washington, Seattle
  29. Denayer, A, Van Esch, H, De Ravel, T, Frijns, JP, Van Buggenhout, G, Vogels, A, Devriendt, K, Geutjens, J, Thiry, P, Swillen, A (2012) Neuropsychopathology in 7 patients with the 22q13 deletion syndrome: presence of bipolar disorder and progressive loss of skills. Mol Syndromol 3: pp. 14-20
  30. Dhar, SU, Del Gaudio, D, German, JR, Peters, SU, Ou, Z, Bader, PI, Berg, JS, Blazo, M, Brown, CW, Graham, BH, Grebe, TA, Lalani, S, Irons, M, Sparagana, S, Williams, M, Phillips, JA, Beaudet, AL, Stankiewicz, P, Patel, A, Cheung, SW, Sahoo, T (2010) 22q13.3 deletion syndrome: clinical and molecular analysis using array CGH. Am J Med Genet A 152A: pp. 573-581 CrossRef
  31. Jeffries, AR, Curran, S, Elmslie, F, Sharma, A, Wenger, S, Hummel, M, Powell, J (2005) Molecular and phenotypic characterization of ring chromosome 22. Am J Med Genet A 137: pp. 139-147 CrossRef
  32. Koolen, DA, Reardon, W, Rosser, EM, Lacombe, D, Hurst, JA, Law, CJ, Bongers, EM, Van Ravenswaaij-Arts, CM, Leisink, MA, Van Kessel, AG, Veltman, JA, De Vries, BB (2005) Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation. Eur J Hum Genet 13: pp. 1019-1024 CrossRef
  33. Luciani, JJ, De Mas, P, Depetris, D, Mignon-Ravix, C, Bottani, A, Prieur, M, Jonveaux, P, Philippe, A, Bourrouillou, G, De Martinville, B, Delobel, B, Vallee, L, Croquette, MF, Mattei, MG (2003) Telomeric 22q13 deletions resulting from rings, simple deletions, and translocations: cytogenetic, molecular, and clinical analyses of 32 new observations. J Med Genet 40: pp. 690-696 CrossRef
  34. Manning, MA, Cassidy, SB, Clericuzio, C, Cherry, AM, Schwartz, S, Hudgins, L, Enns, GM, Hoyme, HE (2004) Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 114: pp. 451-457 CrossRef
  35. Nesslinger, NJ, Gorski, JL, Kurczynski, TW, Shapira, SK, Siegel-Bartelt, J, Dumanski, JP, Cullen, RF, French, BN, McDermid, HE (1994) Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet 54: pp. 464-472
  36. Philippe, A, Boddaert, N, Vaivre-Douret, L, Robel, L, Danon-Boileau, L, Malan, V, de Blois, MC, Heron, D, Colleaux, L, Golse, B, Zilbovicius, M, Munnich, A (2008) Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 122: pp. e376-e382 CrossRef
  37. Soorya, L, Kolevzon, A, Zweifach, J, Lim, T, Dobry, Y, Schwartz, L, Frank, Y, Wang, AT, Cai, G, Parkhomenko, E, Halpern, D, Grodberg, D, Angarita, B, Willner, JP, Yang, A, Canitano, R, Chaplin, W, Betancur, C, Buxbaum, JD (2013) Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Mol Autism 4: pp. 18 CrossRef
  38. Rollins, JD (2011) Growth in Phelan-McDermid syndrome. Am J Hum Genet 155: pp. 2324-2326
  39. Sarasua, SM, Boccuto, L, Sharp, JL, Dwivedi, A, Chen, CF, Rollins, JD, Rogers, RC, Phelan, K, DuPont, BR (2014) Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet 133: pp. 847-859 CrossRef
  40. Sarasua, SM, Dwivedi, A, Boccuto, L, Chen, CF, Sharp, JL, Rollins, JD, Collins, JS, Rogers, RC, Phelan, K, DuPont, BR (2013) 22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome. Genet Med 16: pp. 318-328 CrossRef
  41. Cusmano-Ozog, K, Manning, MA, Hoyme, HE (2007) 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am J Med Genet C: Semin Med Genet 145C: pp. 393-398 CrossRef
  42. Verhoeven, WM, Egger, JI, Willemsen, MH, De Leijer, GJ, Kleefstra, T (2012) Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?. Neuropsychiatr Dis Treat 8: pp. 175-179 CrossRef
  43. Vucurovic, K, Landais, E, Delahaigue, C, Eutrope, J, Schneider, A, Leroy, C, Kabbaj, H, Motte, J, Gaillard, D, Rolland, AC, Doco-Fenzy, M (2012) Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion. Eur J Med Genet 55: pp. 625-629 CrossRef
  44. Sarasua, SM, Dwivedi, A, Boccuto, L, Rollins, JD, Chen, CF, Rogers, RC, Phelan, K, DuPont, BR, Collins, JS (2011) Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome). J Med Genet 48: pp. 761-766 CrossRef
  45. Wilson, HL, Wong, AC, Shaw, SR, Tse, WY, Stapleton, GA, Phelan, MC, Hu, S, Marshall, J, McDermid, HE (2003) Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 40: pp. 575-584 CrossRef
  46. Alpern, GBT, Shearer, M (1986) Developmental Profile II. Western Psychological Services, Los Angeles
  47. Lindquist, SG, Kirchhoff, M, Lundsteen, C, Pedersen, W, Erichsen, G, Kristensen, K, Lillquist, K, Smedegaard, HH, Skov, L, Tommerup, N, Br酶ndum-Nielsen, K (2005) Further delineation of the 22q13 deletion syndrome. Clin Dysmorphol 14: pp. 55-60 CrossRef
  48. Slavotinek, A, Maher, E, Gregory, P, Rowlandson, P, Huson, SM (1997) The phenotypic effects of chromosome rearrangement involving bands 7q21.3 and 22q13.3. J Med Genet 34: pp. 857-861 CrossRef
  49. Tagaya, M, Mizuno, S, Hayakawa, M, Yokotsuka, T, Shimizu, S, Fujimaki, H (2008) Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome. Clin Dysmorphol 17: pp. 19-21 CrossRef
  50. Watt, JL, Olson, IA, Johnston, AW, Ross, HS, Couzin, DA, Stephen, GS (1985) A familial pericentric inversion of chromosome 22 with a recombinant subject illustrating a 鈥榩ure鈥?partial monosomy syndrome. J Med Genet 22: pp. 283-287 CrossRef
  51. Tabolacci, E, Zollino, M, Lecce, R, Sangiorgi, E, Gurrieri, F, Leuzzi, V, Opitz, JM, Neri, G (2005) Two brothers with 22q13 deletion syndrome and features suggestive of the Clark-Baraitser syndrome. Clin Dysmorphol 14: pp. 127-132 CrossRef
  52. Aldinger, KA, Kogan, J, Kimonis, V, Fernandez, B, Horn, D, Klopocki, E, Chung, B, Toutain, A, Weksberg, R, Millen, KJ, Barkovich, AJ, Dobyns, WB (2013) Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A 161A: pp. 131-136 CrossRef
  53. Tsilchorozidou, T, Menko, FH, Lalloo, F, Kidd, A, De Silva, R, Thomas, H, Smith, P, Malcolmson, A, Dore, J, Madan, K, Brown, A, Yovos, JG, Tsaligopoulos, M, Vogiatzis, N, Baser, ME, Wallace, AJ, Evans, DG (2004) Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis 2. J Med Genet 41: pp. 529-534 CrossRef
  54. Zirn, B, Arning, L, Bartels, I, Shoukier, M, Hoffjan, S, Neubauer, B, Hahn, A (2012) Ring chromosome 22 and neurofibromatosis type II: proof of two-hit model for the loss of the NF2 gene in the development of meningioma. Clin Genet 81: pp. 82-87 CrossRef
  55. Trabacca, A, Losito, L, De Rinaldis, M, Gennaro, L (2011) Congenital hypotonia in a child with a de novo 22q13 monosomy and 2pter duplication: a clinical and molecular genetic study. J Child Neurol 26: pp. 235-238 CrossRef
  56. Barakat, AJ, Pearl, PL, Acosta, MT, Runkle, BP (2004) 22q13 deletion syndrome with central diabetes insipidus: a previously unreported association. Clin Dysmorphol 13: pp. 191-194 CrossRef
  57. Kirkpatrick, BE, El-Khechen, D (2011) A unique presentation of 22q13 deletion syndrome: multicystic kidney, orofacial clefting, and Wilms鈥?tumor. Clin Dysmorphol 20: pp. 53-54 CrossRef
  58. Bartsch, O, Schneider, E, Damatova, N, Weis, R, Tufano, M, Iorio, R, Ahmed, A, Beyer, V, Zechner, U, Haaf, T (2010) Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome. Am J Med Genet A 152A: pp. 2099-2102 CrossRef
  59. Tufano, M, Della Corte, C, Cirillo, F, Spagnuolo, MI, Candusso, M, Melis, D, Torre, G, Iorio, R (2009) Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association. Eur J Pediatr 168: pp. 225-227 CrossRef
  60. Redecker, P, Bockmann, J, B枚ckers, TM (2006) Expression of postsynaptic density proteins of the ProSAP/Shank family in the thymus. Histochem Cell Biol 126: pp. 679-685 CrossRef
  61. Chen, CP, Lin, SP, Chern, SR, Tsai, FJ, Wu, PC, Lee, CC, Chen, YT, Chen, WL, Wang, W (2010) A de novo 7.9聽Mb deletion in 22q13.2鈥夆啋鈥塹ter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet 53: pp. 329-332 CrossRef
  62. Bonaglia, MC, Giorda, R, Beri, S, De Agostini, C, Novara, F, Fichera, M, Grillo, L, Galesi, O, Vetro, A, Ciccone, R, Bonati, MT, Giglio, S, Guerrini, R, Osimani, S, Marelli, S, Zucca, C, Grasso, R, Borgatti, R, Mani, E, Motta, C, Molteni, M, Romano, C, Greco, D, Reitano, S, Baroncini, A, Lapi, E, Cecconi, A, Arrigo, G, Patricelli, MG, Pantaleoni, C (2011) Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. PLoS Genet 7: pp. e1002173 CrossRef
  63. Bonaglia, MC, Giorda, R, Borgatti, R, Felisari, G, Gagliardi, C, Selicorni, A, Zuffardi, O (2001) 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 69: pp. 261-268 CrossRef
  64. Boccuto, L, Lauri, M, Sarasua, SM, Skinner, CD, Buccella, D, Dwivedi, A, Orteschi, D, Collins, JS, Zollino, M, Visconti, P, DuPont, B, Tiziano, D, Schroer, RJ, Neri, G, Stevenson, RE, Gurrieri, F, Schwartz, CE (2013) Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet 21: pp. 310-316 CrossRef
  65. Hamdan, FF, Gauthier, J, Araki, Y, Lin, DT, Yoshizawa, Y, Higashi, K, Park, AR, Spiegelman, D, Dobrzeniecka, S, Piton, A, Tomitori, H, Daoud, H, Massicotte, C, Henrion, E, Diallo, O, Shekarabi, M, Marineau, C, Shevell, M, Maranda, B, Mitchell, G, Nadeau, A, D'Anjou, G, Vanasse, M, Srour, M, Lafreni猫re, RG, Drapeau, P, Lacaille, JC, Kim, E, Lee, JR (2011) Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 88: pp. 306-316 CrossRef
  66. Betancur, C, Buxbaum, JD (2013) SHANK3 haploinsufficiency: a 鈥渃ommon鈥?but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol Autism 4: pp. 17 CrossRef
  
• 刊物主题：Neurosciences; Neurobiology; Neuropsychology; Psychiatry; Human Genetics; Pediatrics;
• 出版者：BioMed Central
• ISSN：1866-1955

文摘

Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS.