The Importance of Down Syndrome Phenocopies in the Newborns in Tertiary Obstetric Hospital


  • Elizabeta Zisovska Department of Neonatology, University Clinic for Gynecology and Obstetrics, Faculty of Medicine, Skopje
  • Bratica Lazovska Cytogenetic Laboratory, University Clinic for Gynecology and Obstetrics, Faculty of Medicine, Skopje



dysmorphia, phenocopy, minor anomaly, newborn, Down syndrome.


Background: A phenotype is the composite of the observable characteristics, and in some cases it is not representative for identification of recognized genetic structure.

Aim: The aims of the study were to present the incidence and clinical features of dismorphia in newborn children, and to investigate the prevalence of phenocopies among them.

Material and Methods: Newborns born at the University Clinic for Gynecology & Obstetrics, having at least 3 minor anomalies (mm) specific for Down syndrome were investigated. Patients’ histories, observation, cytogenetic analysis of peripheral blood samples were analysed.

Results: Among 17835 liveborns during 5 years’ period, 128 were detected having at least 3 mm, calculated incidence of dysmorphia 0.83% (1:139). Cytogenetic analysis was not performed in 3.1% (4/128) due to immediate death or transfers elsewhere, 30.5% (39/128) were confirmed Down syndrome. Cytogenetic analysis showed trisomy 21 in 97.4%; Robertsonian translocation had one newborn (2.6%); normal cytogenetic structure had 66.4% (85/128) of the newborns.

Conclusons: Other studies didn’t highlight the proportion of phenocopies of Down syndrome in unselected population of newborns, mainly investigating sick children, disabled, or older-aged. As more the critical role of phenocopy emerges, the more the initial difficulty in detecting gene-gene interactions is amplified. Neglecting the possible presence of phenocopies in complex traits, heavily affects the analysis of their genetic data.


Download data is not yet available.


Metrics Loading ...


Jablonka E. Current Biology: Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution The Quarterly Review of Biology. 2009;84(2): 131-176.

Edwards AW. Human genetic diversity: Lewontin's fallacy. Bio Essays 2003; 25 (8): 798–39 801.

Roll-Hansen, Nils. Sources of Wilhelm Johannsen's Genotype Theory. Journal of the History of Biology. 2009; 42 (3): 457–93.

Lewontin R. The Genotype/Phenotype Distinction, The Stanford Encyclopedia of Philosophy (Summer 2011 Edition), Edward N. Zalta (ed.), URL

Widukund L. Springer-Werlag Humangenetik. 1970; 9:227-229. accessed 2013-08-18.

Landauer W. On phenocopies, their developmental physiology and genetic meaning. American naturalist. 1958; 92(865): 210-215.

Relethford JH. Apportionment of global human genetic diversity based on craniometrics and skin color. Am J Phys Anthropol. 2002; 118 (4): 393–8.

Nachtomy O, et al. Gene expression and the concept of the phenotype. Studies in History and Philosophy of Biological and Biomedical Science. 2007; 38 (1): 238–54.

Jones K. Smith's Recognizable Patterns of Human Malformation. Vol. 4th. WB Saunders Co.: Philadelphia, 1988.

Sumanović-Glamuzina D, Bozić T, Brkić V, Robović A, Saraga-Karacić V. Minor malformations: neonatal or anthropological story? Coll Antropol. 2009; 33(Suppl 2):31-5.

McAdams H, Arkin A. Stochastic Mechanisms in Gene Expression. Proceedings of 10 the National Academy of Sciences, U.S.A., 1997; 94: 814–819.

Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, et al. The Diploid Genome Sequence of an Individual Human. PLoS Biol. 2007; 5 (10): e254.

Aase J. Diagnostic Dysmorphology; Plenum, New York, 1990.

Lerer RJ. Do hyperactive children tend to have abnormal palmar creases? A report of a 16 suggestive association. Clin Pediatr. 1977;16:645-647.

Manica A, Amos W, Balloux F, Hanihara T. The effect of ancient population bottlenecks on human phenotypic variation. Nature. 2007;448 (7151): 346–8.

Lee M. Ethnicity tied to gene expression - The Scientist - Magazine of the Life Sciences. The Scientist. Accessed 2013-01-25.

Common genetic variants account for differences in gene expression among ethnic groups: Abstract: Nature Genetics. Accessed 2013-02-15.

Reich D, Green RE, Kircher M. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010; 468 (7327): 1053–1060.

Waldrop M, Halverson C. Minor physical anomalies and hyperactive behavior in children. In: Hellmuth J (ed) Exceptional Infant: Studies in Abnormalities. Brunner/Mazel: New York, 1971;(2):343-380.

Hoyme H. Minor anomalies: diagnostic clues to aberrant human morphogenesis. Genetica. 1993; 89:307-315.

[Zisovska E. The role of minor anomalies in the early childhood in early recognition of hereditary anomalies and chromozomopathies. [MSc] UKIM: Skopje, 1983]. In Macedonian.

Fontaine CH. Some thoughts about anatomic variations. Surg Radiol Anat. 2001;23: 1-2.

Marden PM, Smith DW, MC Donald MJ. Congenital anomalies in the newborn infant, including minor variants. J Paediatrics. 1964; 64: 357-371.

Stevenson RE, Hall JG. Terminology. Vol I. In: Stevenson RE, Hall JG and Goodman RM (eds). Human malformations and related anomalies. Oxford University Press: London, 1993; pp 21-30.

Mehes K, Stadler G. Minor malformations in the neonate. Akadémiai Kiadó: Budapest, 1983.

William PLT, Humpherson JR. Concepts of variation and normality in morphology: import issues at risk of neglect in modern undergraduate medical courses. Clin Anat. 1999; 4912: 186-190.

Arey LB. Developmental Anatomy. W.B. Saunders Company: Philadelphia and London, 1940.

Down J. Observations on an ethnic classification of idiots. London Hospital Clinical Lecture Reports. 1866; 3:259-262.

Pinsky L. Informative morphogenetic variants: minor congenital anomalies revisited. In: Kalter H, ed. Issues and Reviews in Teratology. Plenum Press: New York,1985;3:135-588.

Accardo PJ, Tomazic T, Morrow J, Haake C, Whitman BY. Minor Malformations, Hyperactivity, and Learning Disabilities. Arch Pediatr Adolesc Med. 1991;145(10):1184-1187.

Hoyme HE. Minor malformations: significant or insignificant? AJDC. 1987;141:947.

Green MF, Satz P, Soper HV, Kharaki F. Relationship between physical anomalies and age of onset of schizophrenia. Am J Psychiatry. 1987;144:666-667.

Miller G. Minor congenital anomalies and ataxic cerebral palsy . Arch Dis Child. 1989;64:557-562.

Drillien C, Drummond M. Developmental Screening and the Child with Special Needs. Philadelphia, Pa: JB Lippincott, 1983.

Pouladfar G, Mallahzadeh A. The Prevalence of minor congenital anomalies and normal variations in neonates in Bushehr port. 2005; 8(1): 43-52.

Tsai FJ, Tsai CH, Peng CT, Wu JY, Lien CH, Wang TR. Different race, different face: minor anomalies in Chinese newborn infants. Acta Paediatr. 1999; 88(3):323-6.

Lescai F, Franceschi C. The Impact of Phenocopy on the Genetic Analysis of Complex Traits. PLoS ONE. 2010; 5(7): e11876.

Trent RJA, Williams R and Sutherland GR. The “new†genetics and clinical practice. MJA. 2003; 178: 406–409.




How to Cite

Zisovska E, Lazovska B. The Importance of Down Syndrome Phenocopies in the Newborns in Tertiary Obstetric Hospital. Open Access Maced J Med Sci [Internet]. 2013 Dec. 15 [cited 2021 Apr. 12];1(1):32-7. Available from:



B - Clinical Sciences