Congenital Malformations and Developmental Changes of the Breast: A Dysmorphological View

  • Paul MerlobEmail author


Congenital malformations of the breast and nipple-areolar complex are described from the aspect of neonatal dysmorphology. Their classification is based on the accepted nomenclature in the medical literature and on our own special method of clinical examination. The developmental changes of the breast are also presented. Except for amastia, polymastia, and polythelia, which have received much attention, the data for many other breast malformations are sparse. Case-control studies or even case series are rare, and good evidence is often lacking. In addition, more studies are needed to complete the map of genes involved in breast development. This information will contribute substantially to our understanding and clinical approach to breast malformations in the future.


  1. 1.
    Spranger J, Benirschke K, Hall JG, Lenz W, Lowry RB, Opitz JM, Pinsky L, Schwarzacher HG, Smith DW. Errors of morphogenesis: concepts and terms. Recommendations of an international working group. J Pediatr. 1983;100(1):160–5.CrossRefGoogle Scholar
  2. 2.
    Hennekam RC, Biesecker LG, Allanson JE, Hall JG, Opitz JM, Temple IK, Carey JC, Elements of Morphology Consortium. Elements of morphology: general terms for congenital anomalies. Am J Med Genet A. 2013;161A(11):2726–33.CrossRefPubMedGoogle Scholar
  3. 3.
    Letterman G, Schurter M. Suggested nomenclature for aesthetic and reconstructive surgery of the breasts: IV. Congenital anomalies of the breast. Aesthetic Plast Surg. 1989;13(1):59–61.CrossRefPubMedGoogle Scholar
  4. 4.
    Merlob P. Congenital malformations and developmental changes of the breast: a neonatological view. J Pediatr Endocrinol Metab. 2003;16(4):471–85.CrossRefPubMedGoogle Scholar
  5. 5.
    Moore KL. The developing human: clinically oriented embryology. 4th ed. Philadelphia: WB Saunders Co.; 1988. p. 426–8.Google Scholar
  6. 6.
    Javed A, Lteif A. Development of the human breast. Semin Plast Surg. 2013;27(1):5–2.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Shermak MA. Congenital and abnormalities of the breast. In: Jatoi I, Kaufmann M, editors. Management of breast diseases. Berlin, Heidelberg: Springer-Verlag; 2010. p. 37–51.CrossRefGoogle Scholar
  8. 8.
    Anbazhagan R, Bartek J, Monaghan P, Gusterson BA. Growth and development of the human infant breast. Am J Anat. 1991;192(4):407–17.CrossRefPubMedGoogle Scholar
  9. 9.
    Schmidt IM, Chellakooty M, Haavisto AM, Boisen KA, Damgaard IN, Steendahl U, Toppari J, Skakkebaek NE, Main KM. Gender difference in breast tissue size in infancy: correlation with serum estradiol. Pediatr Res. 2002;52(5):682–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Trier WC. Complete breast absence: case report and review of the literature. Plast Reconstr Surg. 1965;36(4):431–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Tawil HM, Najjar SS. Congenital absence of the breasts. J Pediatr. 1968;73(5):751–3.CrossRefPubMedGoogle Scholar
  12. 12.
    Bianca S, Licciardello M, Barrano B, Ettore G. Isolated congenital amastia: a subclavian artery supply disruption sequence? Am J Med Genet A. 2010;152A(3):792–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Hamosh A, Scott AF, Amberger J, Bocchini C, Valle D, McKusick VA. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2002;30(1):52–5.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Patil LG, Shivanna NH, Benakappa N, Ravindranath H, Bhat R. Congenital amastia. Indian J Pediatr. 2013;80(10):870–1.CrossRefPubMedGoogle Scholar
  15. 15.
    Jones KL. Smith’s recognizable patterns of human malformations. 5th ed. Philadelphia: WB Saunders Co.; 1997.Google Scholar
  16. 16.
    Ozsoy Z, Gozu A, Ozyigit MT, Genc B. Amazia with midface anomaly: case report. Aesthet Plast Surg. 2007;31(4):392–4.CrossRefGoogle Scholar
  17. 17.
    Papadimitriou A, Karapanou O, Papadopoulou A, Nicolaidou P, Fretzayas A. Congenital bilateral amazia associated with bilateral choanal atresia. Am J Med Genet A. 2009;149A(7):1529–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Dreifuss SE, MacIsaac ZM, Grunwaldt LJ. Bilateral congenital amazia: a case report and systematic review of the literature. J Plast Reconstr Aesthet Surg. 2014;67(1):27–33.CrossRefPubMedGoogle Scholar
  19. 19.
    Nso-Roca AP, Aquirre-Balsalobre FJ, Juste RM. Isolated unilateral amazia: an exceptional breast anomaly. J Pediatr Adolesc Gynecol. 2012;25(6):e147–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Rosen PP. Rosen’s breast pathology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 23–9.Google Scholar
  21. 21.
    Hanson E, Segovia J. Dorsal supernumerary breasts. Plast Reconstr Surg. 1978;61(3):441–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Buyse ML, editor. Birth defects encyclopedia: the comprehensive, systematic, illustrated reference source for the diagnosis, delineation, etiology, biodynamics, occurrence, prevention, and treatment of human anomalies of clinical relevance. Dover, MA: Blackwell Scientific Publications; 1990. p. 246–7.Google Scholar
  23. 23.
    Leung W, Heaton JPW, Morales A. An uncommon urologic presentation of a supernumerary breast. Urology. 1997;50(1):122–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Giron GL, Friedman I, Feldman S. Lobular carcinoma in ectopic axillary breast tissue. Am Surg. 2004;70(4):312–5.PubMedGoogle Scholar
  25. 25.
    Patel RV, Govani D, Patel R, Bhayani B. Adolescent right axillary accessory breast with galactorrhoea. BMJ Case Rep. 2014;2014. pii: bcr2014204215.Google Scholar
  26. 26.
    Hiremath B, Subramaniam N, Chandrashekhar N. Giant accessory breast: a rare occurrence reported, with a review of the literature. BMJ Case Rep. 2015;2015. pii: bcr2015210918.Google Scholar
  27. 27.
    Velanovich V. Fine needle aspiration cytology in the diagnosis and management of ectopic breast tissue. Am Surg. 1995;61(3):277–8.PubMedGoogle Scholar
  28. 28.
    Weinberg SK, Motulksy AG. Aberrant axillary breast tissue: a report of a family with six affected women in two generations. Clin Genet. 1976;10(6):325–8.PubMedGoogle Scholar
  29. 29.
    Cellini A, Offidani A. Familial supernumerary nipples and breasts. Dermatology. 1992;185(1):56–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Deshpande SN, Jagtap SR, Thatte RL. An unusual case of congenital wall deformity with polymastia and absence of part of the lung. Br J Plast Surg. 1989;42(4):484–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Ghosn SH, Khatri KA, Bhawan J. Bilateral aberrant axillary breast tissue mimicking lipomas: report of a case and review of the literature. J Cutan Pathol. 2007;34(Suppl 1):9–13.CrossRefPubMedGoogle Scholar
  32. 32.
    Urbani CE, Betti R. Accessory mammary tissue in clinical practice. Milan: McGraw-Hill; 1996. p. 35–56.Google Scholar
  33. 33.
    Lewis EJ, Crutchfield CE, Ebertz MJ, Prawer SE. Report of a nipple nevus and an overview of accessory mammary tissue. Cutis. 1998;62(5):243–6.PubMedGoogle Scholar
  34. 34.
    DeFilippis EM, Arleo EK. The ABCs of accessory breast tissue: basic information every radiologist should know. AJR Am J Roentgenol. 2014;202(5):1157–62.CrossRefPubMedGoogle Scholar
  35. 35.
    Urbani CE, Betti R. Familial aberrant mammary tissue – a clinico-epidermiological survey of 18 cases. Dermatology. 1995;190(3):207–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Urbani CE, Betti R. Accessory mammary tissue associated with congenital and hereditary nephrourinary malformations. Int J Dermatol. 1996;35(5):349–52.CrossRefPubMedGoogle Scholar
  37. 37.
    Huffman JW, Dewhurst CJ, Caprano VJ. The gynecology of childhood and adolescence. 2nd ed. Philadelphia, PA: WB Saunders Co.; 1981. p. 542–59.Google Scholar
  38. 38.
    Sun J, Qiao Q, Qi K. The difference in estrogen receptor protein level between breast hypertrophy and micromastia. Plast Reconstr Surg. 2004;113(7):2241–2.CrossRefPubMedGoogle Scholar
  39. 39.
    Spear SL, Pelletiere CV, Lee ES, Grotting JC. Anterior thoracic hypoplasia: a separate entity from Poland syndrome. Plast Reconstr Surg. 2004;113(1):69–77.CrossRefPubMedGoogle Scholar
  40. 40.
    Francis GL, Hoffman WH, Gala RR, McPherson JCD, Zadinsky J. A relationship between neonatal breast size and cord blood testosterone level. Ann Clin Lab Sci. 1990;20(4):239–44.PubMedGoogle Scholar
  41. 41.
    Bezzi M, Mitchell DG, Kurtz AB, Ronkin SL, Goldberg BB. Prominent fetal breasts. A normal variant. J Ultrasound Med. 1987;6(11):655–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Mick GJ, McCormick KL, Wakimoto H. Massive breast enlargement in an infant girl with central nervous system dysfunction. Eur J Pediatr. 1991;150(3):154–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Zinn HL, Haller JO, Kedia S. Macromastia in a newborn with Alagille syndrome. Pediatr Radiol. 1999;29(5):331–3.CrossRefPubMedGoogle Scholar
  44. 44.
    Greydanus DE, Parks DS, Farrell EG. Breast disorders in children and adolescents. Pediatr Clin N Am. 1989;36(3):601–38.CrossRefGoogle Scholar
  45. 45.
    Gliosci A, Presutti F. Asymmetry of the breast: some uncommon cases. Aesthet Plast Surg. 1994;18(4):399–403.CrossRefGoogle Scholar
  46. 46.
    Glicksman CA, Ferenz SE. The etiologies of chest wall and breast asymmetry and improvement in breast augmentation. Clin Plast Surg. 2015;42(4):519–30.CrossRefPubMedGoogle Scholar
  47. 47.
    Lawrence RA, Lawrence RM. Breastfeeding: a guide for the medical profession. 5th ed. St. Louis: Mosby; 1999. p. 35–57.Google Scholar
  48. 48.
    Hosokawa K, Hata Y, Yano K, Susuki T, Kikui T, Tahara S. Unilateral athelia with a subcutaneous dermoid cyst. Plast Reconstr Surg. 1987;80(5):732–4.CrossRefPubMedGoogle Scholar
  49. 49.
    Ishida LH, Alves HR, Munhoz AM, Kaimoto C, Ishida LC, Saito FL, Gemperlli R, Ferreira MC. Athelia: case report and review of the literature. Br J Plast Surg. 2005;58(6):833–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Baris H, Tan WH, Kimonis VE. Hypothelia, syndactyly, and ear malformation--a variant of the scalp-ear-nipple syndrome?: Case report and review of the literature. Am J Med Genet A. 2005;134A(2):220–2.CrossRefPubMedGoogle Scholar
  51. 51.
    Mollica F, Mazzone D, Cimino G, Opitz JM. Severe case of Al Awadi/Raas-Rothschild syndrome or new, possibly autosomal recessive facio-skeleto-genital syndrome. Am J Med Genet. 1995;56(2):168–72.CrossRefPubMedGoogle Scholar
  52. 52.
    Greenberg F. Choanal atresia and athelia: methimazole teratogenicity or a new syndrome? Am J Med Genet. 1987;28(4):931–4.CrossRefPubMedGoogle Scholar
  53. 53.
    Douchement D, Rakza T, Holder M, Bonne NX, Fayoux P. Choanal atresia associated with tracheoesophageal fistula: the spectrum of carbimazole embryopathy. Pediatrics. 2011;128(3):e703–6.PubMedGoogle Scholar
  54. 54.
    Foley J, Dann P, Hong J, Cosgrove J, Dreyer B, Rimm D, Dunbar M, Philbrick W, Wysolmerski J. Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development. 2001;128(4):513–25.PubMedGoogle Scholar
  55. 55.
    Borck G, de Vries L, Wu HJ, Smirin-Yosef P, Nürnberg G, Lagovsky I, Ishida LH, Thierry P, Wieczorek D, Nürnberg P, Foley J, Kubisch C, Basel-Vanagaite L. Homozygous truncating PTPRF mutation causes athelia. Hum Genet. 2014;133(8):1041–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Schmidt H. Supernumerary nipples: prevalence, size, sex and side predilection -- a prospective clinical study. Eur J Pediatr. 1998;157(10):821–3.CrossRefPubMedGoogle Scholar
  57. 57.
    Mehregan AH. Supernumerary nipple. A histologic study. J Cutan Pathol. 1981;8(2):96–104.CrossRefPubMedGoogle Scholar
  58. 58.
    Mimouni F, Merlob P, Reisner SH. Occurrence of supernumerary nipples in newborns. Am J Dis Child. 1983;137(10):952–3.PubMedGoogle Scholar
  59. 59.
    Jaber L, Merlob P. The prevalence of supernumerary nipples in Arab infants and children. Eur J Pediatr. 1988;147(4):443.CrossRefPubMedGoogle Scholar
  60. 60.
    Metzker A. Supernumerary nipple. 735.htm. Accessed 7 May 2015.
  61. 61.
    Leung AKC, Robson LM. Polythelia. Int J Dermatol. 1989;28(7):429–33.CrossRefPubMedGoogle Scholar
  62. 62.
    Hall BK. Atavismus and atavistic mutations. Nat Genet. 1995;10(2):126–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Hersh JH, Bloom AS, Cromer AO, Harrison HL, Weisskopf B. Does a supernumerary nipple/renal field defect exist? Am J Dis Child. 1987;141(9):989–91.Google Scholar
  64. 64.
    Toumbis-Joannou E, Cohen PR. Familial polythelia. J Am Acad Dermatol. 1994;30(4):667–8.CrossRefGoogle Scholar
  65. 65.
    Urbani CE, Betti R. The significance of familial polythelia. J Am Acad Dermatol. 1995;32(4):687–8.CrossRefPubMedGoogle Scholar
  66. 66.
    Urbani CE, Betti R. Sporadic unilateral intra-areolar polythelia. Acta Derm Venerol. 1996;76(2):156.PubMedGoogle Scholar
  67. 67.
    Arranz López JL, García L, Elena E, Benito P, De Juan A. Unilateral dichotomy of nipple (intraareolar polythelia) and areola: report of a case and surgical correction. Aesthet Plast Surg. 2006;30(4):494–6.CrossRefGoogle Scholar
  68. 68.
    Jain M, Jain S, Roy S. Intra-areolar polythelia in pregnancy: a rare anomaly. J Obstet Gynaecol. 2013;33(8):626–32.CrossRefPubMedGoogle Scholar
  69. 69.
    Rintala A, Norio R. Familial intra-areolar polythelia with mammary hypoplasia. Scand J Plast Reconstr Surg. 1982;16(3):287–91.CrossRefPubMedGoogle Scholar
  70. 70.
    Shewmake SW, Izuno GT. Supernumerary areolae. Arch Dermatol. 1977;113(6):823–5.CrossRefPubMedGoogle Scholar
  71. 71.
    Sivan Y, Merlob P, Reisner SH. Sternum length, torso length and internipple distance in newborn infants. Pediatrics. 1983;72(4):523–5.PubMedGoogle Scholar
  72. 72.
    Hassan Z, Karna P, Dolanski EA. Intermamillary indices in premature infants. Am J Perinatol. 1988;5(1):54–6.CrossRefPubMedGoogle Scholar
  73. 73.
    Leung AK, Kao CP, Sauve RS, Fang JH, Leong AG, Liu EK. Internipple distance and internipple index. J Natl Med Assoc. 2004;96(8):1092–6.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Fleisher DS. Lateral displacement of the nipple, a sign of bilateral renal hypoplasia. J Pediatr. 1966;69(5):806–9.CrossRefPubMedGoogle Scholar
  75. 75.
    Han S, Hong YG. The inverted nipple: its grading and surgical correction. Plast Reconstr Surg. 1999;104(2):384–95.CrossRefGoogle Scholar
  76. 76.
    Schwager RG, Smith JW, Gray GF, Goulian DJ. Inversion of the human female nipple, with a simple method of treatment. Plast Reconstr Surg. 1974;54(5):564–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Park HS, Yoon CH, Kim HJ. The prevalence of congenital inverted nipples. Aesthet Plast Surg. 1999;23(2):144–6.CrossRefGoogle Scholar
  78. 78.
    Crestinu JM. Inverted nipple: the new method of correction. Aesthet Plast Surg. 1989;13(3):189–97.CrossRefGoogle Scholar
  79. 79.
    Shafir R, Bonne-Tamir B, Ashbel S, Tsur H, Goodman RM. Genetic studies in a family with inverted nipples (mammillae invertita). Clin Genet. 1979;15(4):346–50.CrossRefPubMedGoogle Scholar
  80. 80.
    Scholten E. A contemporary correction of inverted nipples. Plast Reconstr Surg. 2001;107(2):511–3.CrossRefPubMedGoogle Scholar
  81. 81.
    Gould DJ, Nadeau MH, Macias LH, Stevens WG. Inverted nipple repair revisited: a 7-year experience. Aesthet Surg J. 2015;35(2):156–64.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of NeonatologySchneider Children’s Medical Center and Rabin Medical CenterTetach TikvaIsrael
  2. 2.Tel-Aviv UniversityTel-AvivIsrael

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