The topic of this book is small supernumerary marker chromosomes (sSMC). In this chapter sSMC are introduced, defined, and information is given on their nomenclature, shapes, the frequencies with which they appear, and their effects due to induced gain of copy number, correlation with uniparental disomy, and mosaicism. Also some basics on cytogenetics are provided.


Down Syndrome Turner Syndrome Acrocentric Chromosome Angelman Syndrome Fertility Problem 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Arnold J (1879) Beobachtungen über Kernteilungen in Zellen der Geschwülste. Virchows Arch Pathol Anat 78:279–301CrossRefGoogle Scholar
  2. Backx L, Van Esch H, Melotte C, Kosyakova N, Starke H, Frijns JP, Liehr T, Vermeesch JR (2007) Array painting using microdissected chromosomes to map chromosomal breakpoints. Cytogenet Genome Res 116:158–166PubMedCrossRefGoogle Scholar
  3. Baldwin EL, May LF, Justice AN, Martin CL, Ledbetter DH (2008) Mechanisms and consequences of small supernumerary marker chromosomes: from Barbara McClintock to modern genetic-counseling issues. Am J Hum Genet 82:398–410PubMedCrossRefGoogle Scholar
  4. Barber JC (2005) Directly transmitted unbalanced chromosome abnormalities and euchromatic variants. J Med Genet 42:609–629PubMedCrossRefGoogle Scholar
  5. Barber JC (2011) Chromosome anomaly collection. Cited 10 Jan 2011
  6. Beverstock GC, Bezrookove V, Mollevanger P, van de Kamp JJ, Pearson P, Kouwenberg JM, Rosenberg C (2003) Multiple supernumerary ring chromosomes of different origin in a patient: a clinical report and review of the literature. Am J Med Genet A 122:168–173CrossRefGoogle Scholar
  7. Caspersson T, Farber S, Foley GE, Kudynowski J, Modest EJ, Simonsson E, Wagh U, Zech L (1968) Chemical differentiation along metaphase chromosomes. Exp Cell Res 49:219–222PubMedCrossRefGoogle Scholar
  8. Cavani S, Malcarne M, Arlanian A, Stagni L, Piombo G, Baldo C, Scaraglio T, Boggio G, Mogni M, Uras A, Alabiso A, Zucca M, Zerrega G, Dagna Briscarelli F, Pierluigi M (2003) Prenatal and postnatal identification of 93 supernumerary small chromosomes. Annales de Genetique 46:231 (Abstract Number 7.19)Google Scholar
  9. Chandley AC, Edmond P, Christie S, Gowans L, Fletcher J, Frackiewicz A, Newton M (1975) Cytogenetics and infertility in man. I. Karyotype and seminal analysis: results of a five-year survey of men attending a subfertility clinic. Ann Hum Genet 39:231–254PubMedCrossRefGoogle Scholar
  10. Chudoba I, Franke Y, Senger G, Sauerbrei G, Demuth S, Beensen V, Neumann A, Hansmann I, Claussen U (1999) Maternal UPD 20 in a hyperactive child with severe growth retardation. Eur J Hum Genet 7:533–540PubMedCrossRefGoogle Scholar
  11. Créau-Goldberg N, Gegonne A, Delabar J, Cochet C, Cabanis MO, Stehelin D, Turleau C, de Grouchy J (1987) Maternal origin of a de novo balanced t(21q21q) identified by ets-2 polymorphism. Hum Genet 76:396–398PubMedCrossRefGoogle Scholar
  12. Crolla JA, Howard P, Mitchell C, Long FL, Dennis NR (1997) A molecular and FISH approach to determining karyotype and phenotype correlations in six patients with supernumerary marker(22) chromosomes. Am J Med Genet A 72:440–447CrossRefGoogle Scholar
  13. Crolla JA (1998) FISH and molecular studies of autosomal supernumerary marker chromosomes excluding those derived from chromosome 15: II. Review of the literature. Am J Med Genet A 75:367–381CrossRefGoogle Scholar
  14. Crolla JA, Youings SA, Ennis S, Jacobs PA (2005) Supernumerary marker chromosomes in man: parental origin, mosaicism and maternal age revisited. Eur J Hum Genet 13:154–160PubMedCrossRefGoogle Scholar
  15. Daniel A, Malafiej P (2003) A series of supernumerary small ring marker autosomes identified by FISH with chromosome probe arrays and literature review excluding chromosome 15. Am J Med Genet A 117:212–222CrossRefGoogle Scholar
  16. Ellis JR, Marshall R, Penrose LS (1962) An aberrant small acrocentric chromosome. Ann Hum Genet 26:77–83PubMedCrossRefGoogle Scholar
  17. Engel E (1980) A new genetic concept: uniparental disomy and its potential effect, isodisomy. Am J Med Genet A 6:137–143CrossRefGoogle Scholar
  18. Fickelscher I, Starke H, Schulze E, Ernst G, Kosyakova N, Mkrtchyan H, Macdermont K, Sebire N, Liehr T (2007) A further case with a small supernumerary marker chromosome (sSMC) derived from chromosome 1-evidence for high variability in mosaicism in different tissues of sSMC carriers. Prenat Diagn 27:783–785PubMedCrossRefGoogle Scholar
  19. Forster T, Roy D, Ghazal P (2003) Experiments using microarray technology: limitations and standard operating procedures. J Endocrinol 178:195–204PubMedCrossRefGoogle Scholar
  20. Friedrich U, Nielsen J (1974) Bisatellited extra small metacentric chromosome in newborns. Clin Genet 6:23–31PubMedCrossRefGoogle Scholar
  21. Froland A, Holst G, Terslev E (1963) Multiple anomalies associated with an extra small autosome. Cytogenetics 2:99–106CrossRefGoogle Scholar
  22. Graf MD, Christ L, Mascarello JT, Mowrey P, Pettenati M, Stetten G, Storto P, Surti U, Van Dyke DL, Vance GH, Wolff D, Schwartz S (2006) Redefining the risks of prenatally ascertained supernumerary marker chromosomes: a collaborative study. J Med Genet 43:660–664PubMedCrossRefGoogle Scholar
  23. Hahn M, Dambacher S, Schotta G (2010) Heterochromatin dysregulation in human diseases. J Appl Physiol 109:232–342PubMedCrossRefGoogle Scholar
  24. Ilberry PLT, Lee CWG, Winn SM (1961) Incomplete trisomy in a mongoloid child exhibiting minimal stigmata. Med J Austr 48:182–184Google Scholar
  25. Ing PS, Lubinsky MS, Smith SD, Golden E, Sanger WG, Duncan A (1987) Cat-eye syndrome with different marker chromosomes in a mother and daughter. Am J Med Genet A 26:621–628CrossRefGoogle Scholar
  26. Shaffer LG, Slovak ML, Campbell LJ (eds) (2009) ISCN 2009: an international system for human cytogenetic nomenclature. S. Karger, BaselGoogle Scholar
  27. Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821PubMedCrossRefGoogle Scholar
  28. Kotzot D (2002) Supernumerary marker chromosomes (SMC) and uniparental disomy (UPD): coincidence or consequence? J Med Genet 39:775–778PubMedCrossRefGoogle Scholar
  29. Kumar C, Kleyman SM, Samonte RV, Verma RS (1997) Marker chromosomes in fetal loss. Hum Reprod 12:1321–1324PubMedCrossRefGoogle Scholar
  30. Lejeune J (1959) Chromosomic diagnosis of mongolism. Ann Genet Sem Hop 1:41–49Google Scholar
  31. Liehr T (2006) Familial small supernumerary marker chromosomes are predominantly inherited via the maternal line. Genet Med 8:459–462PubMedCrossRefGoogle Scholar
  32. Liehr T (ed) (2009a) Fluorescence in situ hybridization (FISH): application guide. Springer, BerlinGoogle Scholar
  33. Liehr T (2009b) Small supernumerary marker chromosomes (sSMCs): a spotlight on some nomenclature problems. J Histochem Cytochem 57:991–993PubMedCrossRefGoogle Scholar
  34. Liehr T (2010) Cytogenetic contribution to uniparental disomy (UPD). Mol Cytogenet 3:8PubMedCrossRefGoogle Scholar
  35. Liehr T (2011) The sSMC homepage. Cited 10 Jan 2011
  36. Liehr T (2011a) Homepage on multicolor fluorescence in situ hybridization (mFISH) literature. Cited 10 Jan 2011
  37. Liehr T (2011b) Homepage on Cases with uniparental disomy (UPD). Cited 10 Jan 2011
  38. Liehr T, Claussen U (2002) Current developments in human molecular cytogenetic techniques. Curr Mol Med 2:283–297PubMedCrossRefGoogle Scholar
  39. Liehr T, Weise A (2007) Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 19:719–731PubMedGoogle Scholar
  40. Liehr T, Claussen U, Starke H (2004) Small supernumerary marker chromosomes (sSMC) in humans. Cytogenet Genome Res 107:55–67PubMedCrossRefGoogle Scholar
  41. Liehr T, Starke H, Heller A, Kosyakova N, Mrasek K, Gross M, Karst C, Steinhaeuser U, Hunstig F, Fickelscher I, Kuechler A, Trifonov V, Romanenko SA, Weise A (2006a) Multicolor fluorescence in situ hybridization (FISH) applied for FISH-banding. Cytogenet Genome Res 114:240–244PubMedCrossRefGoogle Scholar
  42. Liehr T, Mrasek K, Weise A, Dufke A, Rodríguez L, Martínez Guardia N, Sanchís A, Vermeesch JR, Ramel C, Polityko A, Haas OA, Anderson J, Claussen U, von Eggeling F, Starke H (2006b) Small supernumerary marker chromosomes: progress towards a genotype-phenotype correlation. Cytogenet Genome Res 112:23–34PubMedCrossRefGoogle Scholar
  43. Liehr T, Starke H, Senger G, Melotte C, Weise A, Vermeesch JR (2006c) Overrepresentation of small supernumerary marker chromosomes (sSMC) from chromosome 6 origin in cases with multiple sSMC. Am J Med Genet A 140:46–51PubMedGoogle Scholar
  44. Liehr T, Utine GE, Trautmann U, Rauch A, Kuechler A, Pietrzak J, Bocian E, Kosyakova N, Mrasek K, Boduroglu K, Weise A, Aktas D (2007a) Neocentric small supernumerary marker chromosomes (sSMC): three more cases and review of the literature. Cytogenet Genome Res 118:31–37PubMedCrossRefGoogle Scholar
  45. Liehr T, Mrasek K, Hinreiner S, Reich D, Ewers E, Bartels I, Seidel J, Emmanuil N, Petesen M, Polityko A, Dufke A, Iourov I, Trifonov V, Vermeesch J, Weise A (2007b) Small supernumerary marker chromosomes (sSMC) in patients with a 45, X/46, X,+mar karyotype: 17 new cases and a review of the literature. Sex Dev 1:353–362PubMedCrossRefGoogle Scholar
  46. Liehr T, Mrasek K, Kosyakova N, Ogilvie CM, Vermeesch J, Trifonov V, Rubtsov N (2008a) Small supernumerary marker chromosomes (sSMC) in humans; are there B chromosomes hidden among them. Mol Cytogenet 1:12PubMedCrossRefGoogle Scholar
  47. Liehr T, Wegner R-D, Stumm M, Joksi G, Polityko A, Kosyakova N, Ewers E, Reich D, Wagner R, Weise A (2008b) Pallister-Killian syndrome. Rare phenotypic features and variable karyotypes. Balk J Med Gen 11:65–67Google Scholar
  48. Liehr T, Karamysheva T, Merkas M, Brecevic L, Hamid AB, Ewers E, Mrasek K, Kosyakova N, Weise A (2010a) Somatic mosaicism in cases with small supernumerary marker chromosomes. Curr Genomics 11:432–439PubMedCrossRefGoogle Scholar
  49. Liehr T, Kosyakova N, Weise A, Ziegler M, Raabe-Meyer G (2010b) First case of a neocentromere formation in an otherwise normal chromosome 7. Cytogenet Genome Res 128:189–191PubMedCrossRefGoogle Scholar
  50. Manvelyan M, Riegel M, Santos M, Fuster C, Pellestor F, Mazaurik ML, Schulze B, Polityko A, Tittelbach H, Reising-Ackermann G, Belitz B, Hehr U, Kelbova C, Volleth M, Gödde E, Anderson J, Küpferling P, Köhler S, Duba HC, Dufke A, Aktas D, Martin T, Schreyer I, Ewers E, Reich D, Mrasek K, Weise A, Liehr T (2008) Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature. Int J Mol Med 21:705–714PubMedGoogle Scholar
  51. Mau-Holzmann UA (2005) Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res 111:317–336PubMedCrossRefGoogle Scholar
  52. Maurer B, Haaf T, Stout K, Reissmann N, Steinlein C, Schmid M (2001) Two supernumerary marker chromosomes, originating from chromosomes 6 and 11, in a child with developmental delay and craniofacial dysmorphism. Cytogenet Cell Genet 93:182–187PubMedCrossRefGoogle Scholar
  53. Murmann AE, Conrad DF, Mashek H, Curtis CA, Nicolae RI, Ober C, Schwartz S (2009) Inverted duplications on acentric markers: mechanism of formation. Hum Mol Genet 18:2241–2256PubMedCrossRefGoogle Scholar
  54. Nelle H, Schreyer I, Ewers E, Mrasek K, Kosyakova N, Merkas M, Hamid AB, Weise A, Liehr T (2010) Harmless familial small supernumerary marker chromosome 22 hampers diagnosis of fragile X-syndrome. Mol Med Reports 3:571–574Google Scholar
  55. Nietzel A, Albrecht B, Starke H, Heller A, Gillessen-Kaesbach G, Claussen U, Liehr T (2003) Partial hexasomy 15pter–>15q13 including SNRPN and D15S10: first molecular cytogenetically proven case report. J Med Genet 40:e28PubMedCrossRefGoogle Scholar
  56. Niksic SB, Deretic VI, Pilic GR, Ewers E, Merkas M, Ziegler M, Liehr T (2010) Trisomy 21 with a small supernumerary marker chromosome derived from chromosomes 13/21 and 18. Balk J Med Genet 13:55–58Google Scholar
  57. Online Mendelian Inheritance of Man (OMIM) (2011) Cited 10 Jan 2011
  58. Oracova E, Musilova P, Kopecna O, Rybar R, Vozdova M, Vesela K, Rubes J (2009) Sperm and embryo analysis in a carrier of supernumerary inv dup(15) marker chromosome. J Androl 30:233–239PubMedCrossRefGoogle Scholar
  59. Paoloni-Giacobino A, Morris MA, Dahoun SP (1998) Prenatal supernumerary r(16) chromosome characterized by multiprobe FISH with normal pregnancy outcome. Prenat Diagn 18:751–752PubMedCrossRefGoogle Scholar
  60. Pietrzak J, Mrasek K, Obersztyn E, Stankiewicz P, Kosyakova N, Weise A, Cheung SW, Cai WW, von Eggeling F, Mazurczak T, Bocian E, Liehr T (2007) Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8, 18, and 21 in three patients. J Appl Genet 48:167–175PubMedCrossRefGoogle Scholar
  61. Pinkel D, Straume T, Gray JW (1986) Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A 83:2934–2938PubMedCrossRefGoogle Scholar
  62. Rivera H, Moller M, Hernandez A, Enriquez-Guerra MA, Arreola R, Cantu JM (1984) Tetrasomy 18p: a distinctive syndrome. Ann Genet 27:187–189PubMedGoogle Scholar
  63. Seabright M (1971) A rapid banding technique for human chromosomes. Lancet 2:971–972PubMedCrossRefGoogle Scholar
  64. Shaffer BL, Caughey AB, Cotter PD, Norton ME (2004) Variation in the decision to terminate pregnancy in the setting of an abnormal karyotype with uncertain significance. In: Abstractbook of the 54th annual meeting of the American Society of Human Genetics, p 494 (Abstract Number 2756)Google Scholar
  65. Stanyon R, Rocchi M, Capozzi O, Roberto R, Misceo D, Ventura M, Cardone MF, Bigoni F, Archidiacono N (2008) Primate chromosome evolution: ancestral karyotypes, marker order and neocentromeres. Chromosome Res 16:17–39PubMedCrossRefGoogle Scholar
  66. Stephane P, Genevieve L (1999) Prenatal supernumerary r(16) chromosome characterized by multiprobe FISH with normal pregnancy outcome. Prenat Diagn 19:181–182PubMedCrossRefGoogle Scholar
  67. Tabor HK, Cho MK (2007) Ethical implications of array comparative genomic hybridization in complex phenotypes: points to consider in research. Genet Med 9:626–631PubMedCrossRefGoogle Scholar
  68. ten Bosch JR, Grody WW (2008) Keeping up with the next generation: massively parallel sequencing in clinical diagnostics. J Mol Diagn 10:484–492PubMedCrossRefGoogle Scholar
  69. Tjio JH, Levan A (1956) The chromosome number of man. Hereditas 42:1–6CrossRefGoogle Scholar
  70. Trifonov V, Fluri S, Binkert F, Nandini A, Anderson J, Rodriguez L, Gross M, Kosyakova N, Mkrtchyan H, Ewers E, Reich D, Weise A, Liehr T (2008) Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity? Mol Cytogenet 1:6PubMedCrossRefGoogle Scholar
  71. Tsuchiya KD, Opheim KE, Hannibal MC, Hing AV, Glass IA, Raff ML, Norwood T, Torchia BA (2008) Unexpected structural complexity of supernumerary marker chromosomes characterized by microarray comparative genomic hybridization. Mol Cytogenet 1:7PubMedCrossRefGoogle Scholar
  72. Tuna M, Knuutila S, Mills GB (2009) Uniparental disomy in cancer. Trends Mol Med 15:120–128PubMedCrossRefGoogle Scholar
  73. von Beust G, Sauter SM, Liehr T, Burfeind P, Bartels I, Starke H, von Eggeling F, Zoll B (2005) Molecular cytogenetic characterization of a de novo supernumerary ring chromosome 7 resulting in partial trisomy, tetrasomy, and hexasomy in a child with dysmorphic signs, congenital heart defect, and developmental delay. Am J Med Genet A 137:59–64Google Scholar
  74. Warburton D (1984) Outcome of cases of de novo structural rearrangements diagnosed at amniocentesis. Prenat Diagn 4 Spec No:69–80Google Scholar
  75. Warburton D (1991) De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet A 49:995–1013Google Scholar
  76. Warburton PE (2004) Chromosomal dynamics of human neocentromere formation. Chromosome Res 12:617–626PubMedCrossRefGoogle Scholar
  77. Wolff DJ, Schwartz S (1992) Characterization of Robertsonian translocations by using fluorescence in situ hybridization. Am J Hum Genet A 50:174–181Google Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Institut für HumangenetikUniversitätsklinikum JenaJenaGermany

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