Congenital Anomalies of the Extremities, Nomenclature and the Thalidomide Episode


A recent issue of the Inter-Clinic Information Bulletin (July-August, 1962) was devoted to an English translation of Dr. Oscar Hepp's report on Thalidomide-related anomalies of the extremities in West Germany. These drug-induced congenital anomalies are not the exclusive problem of European, Canadian and South American Clinics. We have already seen four such infants in our clinic and others are scheduled to be seen in the future. It is likely that most of the clinics participating in the Child Amputee program will provide services for some of these children.

In view of our effort to keep abreast of the Thalidomide problem at the Institute, our attempt to re-classify the limb-anomalies of more than 300 of our patients and our interest in a unique aspect of the drug-induced anomalies , we have elected to discuss briefly certain aspects of congenital limb-deformity related to Thalidomide, some problems of nomenclature and recording, and also to provide a bibliography of the scientific publications devoted to Thalidomide and congenital anomalies.

Although the general public is now aware that a chemical compound can produce congenital anomalies of the extremities if taken at the appropriate time in gestation, many people are not aware that these anomalies have been occurring since the dawn of recorded human history, in sporadic or hereditary pattern.

Etiological Factors

For the first time a definitive etiological relationship has been established for a large group of congenital anomalies of the extremities of man. The unanswered question of paramount importance is: What are the etiological factors which produced sporadic cases of deformities for thousands of years prior to Thalidomide and will undoubtedly produce more in the future?

The human fetus, of course, has certain nutritional requirements. It is possible that the nutritional requirements differ not only at different stages of development, but the requirements of one organ system may be significantly different from that of another. It has been learned from experimental animal teratology that skeletal defects can be produced by either an excess or a deficiency of many substances. The teratogenic agents include certain vitamins, hormones and a host of chemical compounds. Experience has also shown the necessity for administyation of the compound at the strategic time in development in order to produce an effect in a given organ system.

The defects produced by Thalidomide have emphasized that constitutional differences in individuals may influence the response to a given dosage of teratogenic agent. For example we have seen a pair of dizygotic twins whose mother took Thalidomide during the first two months of the gestation period. The male twin (Figure I, Patient 2) was born with bilateral upper extremity proximal phocomelia. The female twin was born with duodenal atresia and, except for a hypoplastic right thumb, the extremities were normal. The twins birth weights were essentially the same; hence it is difficult to entertain the idea that one twin received a larger amount of drug because of an arteriovenus shunt. On the other hand, Dr. Widukind Lenz, research scientist in human eugenics at Hamburg University, has observed identical involvement in twins. These are interesting problems which require study.

Problems of Nomenclature and Anatomic Description of the Deformities

Frantz and O?Rahilly (1) have suggested a rational nomenclature which is based on the anatomy of the extremity deficiency or anomaly. This terminology was used effectively in their 1961 account of anomalies of the extremities in 300 children seen in the Michigan Area Child Amputee Center. Recently, efforts have been made (Hall et al) (2) to simplify the classification of Frantz and O?Rahilly and to base it on "the embryological somitic origin of the limb." We have found a system relating appendicular skeletal defects to a somitic basis to be confusing, since the bones of the extremities have no somitic origin and are derived from mesoblastic condensation in the center of the limbbud. The skeletal defects therefore would not be related to dermatomal segments.

The bibliography related to Thalidomide and anomalies of the extremities appearing on pages 7-10 points up the need for a uniform nomenclature. For example, Dr. A. L. Speirs, of Scotland, described one of ten patients with drug-induced anomalies as follows: "amelia of the arms, tag on left shoulder, miniature right forearm with finger tags." He apparently used the word arm as synonymous with upper limb or extremity. Very few writers have utilized the subclassifications of Phocomelia suggested by Frantz and O?Rahilly (complete, (3) proximal (4) and distal (5)).

These remarks are not offered in a critical vein but we must take into consideration the fact that the Thalidomide problem has created thousands of new cases of anomalies of the extremities, and the patients, in some instances, are being treated and written about by physicians who have had little prior contact with such deformities. In order to understand the specific deformities and achieve the maximum educational and scientific benefit from this large new group of patients, it is essential that a common nomenclature be used in case descriptions.

At the Institute of Physical Medicine and Rehabilitation, we have found it impossible to be certain of the skeletal anomalies on the basis of clinical examination of the extremity. Roentgenograms must be made routinely and even then it is sometimes difficult to identify a partially formed anomalous bone.

When one considers the many combinations of limb deformities which are possible, it is apparent that accurate and complete recording of deficiencies is a difficult but nevertheless essential task. In considering only the presence of any of the three subclassifications of phocomelia in combination with a normal extremity, 256 different associations are possible. The possible combinations extend to many thousands of variations when considering the combination of distal phocomelia with partial phocomelia and other types of deformities.

In re-classifying our patients we have found the form on page 6 to be quite useful. All bone deficiencies identified in clinical and roentgenogram examinations are recorded; with additional defects described under "comments." Thus the complete syndrome for each patient is readily available. Each case is then classified on the basis of the Frantz-O?Rahilly nomenclature.

Four infants whose mothers were given Thalidomide during pregnancy have been seen in our clinic. Table I presents the pertinent clinical data and anatomical classification of their anomalous extremities. Figure I is a reproduction of a tracing of the roentgenograms of the anomalous extremities of the four infants.

A Unique Aspect of the Management Problem

The prosthetic aspects of Thalidomide deformities are not different from those of similar anomalies of pre-Thalidomide days and will not be discussed in this article. There are, however, unique psychological problems identifiable in the families affected by the drug.

In the deformities originating in the pre-Thalidomide days or sporadic cases unrelated to the drug, the psycho-social problems of the parents were shrouded in the anxiety expressed in the parental questions: "Why did this happen to me?" or "What did I do, or not do, that could have caused this abnormality?" With the Thalidomide deformities, however, there is a definitive offending agent. There are feelings of self-guilt or of responsibility projected to others. We have seen the husband try to relieve his wife?s feelings by insisting that his personal inadequacy accounted for his wife?s need for the drug. There is also the possibility of the feeling being projected toward the physician who prescribed the drug.

The actual prosthetic care of these patients may start when the infant is six months old but it is important that the rehabilitation management begin with the parent immediately after the birth of the baby. Effective parental counseling at this time will provide better acceptance of the child, reduce anxiety and uncertainty, and prepare the parent to accept a prosthetic appliance program when the infant is ready for it.

A Recent Article of Interest

Attention of our readers is drawn to a leading article in The Lancet, No. 7251, Vol. II, August 18, 1962, entitled "Thalidomide: Part 2." Much of the world-wide publicity accorded the thalidomide-phocomelia disaster has been of a negative nature and the positive approach presented in The Lancet is overdue.

The article raises two basic questions: (1) how can assistance best be provided for the affected children and their parents; and (2) how can similar catastrophies be avoided in the future.

In answer to the first question, The Lancet suggests the following: (1) Establishment of a central registry of cases to determine the precise extent of the problem in England (now estimated at 500 children); (2) Provision for early fitting of prostheses; (3) Development of continuing, multidisciplinary programs of training, education and guidance, perhaps on a regional basis; (4) Support and encouragement of the parents.

On the prevention of similar problems in the future, The Lancet endorses the need for tighter controls on the distribution of new drugs. The article points out, however, that as in the case of thalidomide, laboratory tests on animals may not reveal the toxic effects of a drug on humans, particularly the human fetus. "Human pregnancy," it declares, "may prove to be the most sensitive toxicity test of all." The only safe course to follow is to avoid the use of new drugs during the first trimester of pregnancy.



  1. Frantz, Charles H., M.D., and O?Rahilly, Ronan, M.D., "Congenital Skeletal Limb Deficiencies," The Journal of Bone and Joint Surgery, 43-A, 8, December 1961.
  2. (2) Hall, C. B., Brooks, M. B., and Dennis, J. F., "Congenital Skeletal Deficiencies of the Extremities-(Classification and Fundamentals of Treatment)," The Journal of the American Medical Association, 181-7, August 18, 1962.
  3. (3) Hand or Foot Attached Directly to Trunk.
  4. (4) Hand or Forearm, or Foot and Leg, Attached Directly to Trunk.
  5. (5) Hand or Foot Attached Directly to Arm or Thigh.



(Chronologically Arranged)

  1. Kosenow, W. and Pfeiffer, R. A.: Micromelia, Haemangioma und Duodenal Stenosis Exhibit, German Pediatric Society, Kassel, 1960; reported by title in Monat, Kinderheilk 109:227 (Mar.) 1961.
  2. Wiedemann, H. R.: Himweis auf eine derzeitige, Haufung hypo-und aplastischer Fehlbildunger der Gliedmassen, Med Welt 37:1863-1866 (Sept. 16) 1961.
  3. McBride, W. G.: Thalidomide and congenital abnormalities, Lancet 2:1358 (Dec. 16) 1961.
  4. Lenz, W.: Kindliche Missbildungen nach Medikament wahrend der Graviditat, Deutsch Med Wschr 86:2555-2556 (Dec. 29) 1961.
  5. Pfeiffer, R. A. and Kosenow, W.: Zur Frage einer exogenen Verursachung von schweren Extremitatenmissbildungen, Muench Med Wschr 104:68-74, 1962.
  6. Wiedemann, H. R., and Aeissen, K.: Zur Frage der derzeitigen Haufung von Gliedmassen-Fehbildungen, Med Mschr 12:816-818, 1962.
  7. Hayman, D. J.: Thalidomide and congenital abnormalities, Lancet 1:45 (Jan. 6) 1962.
  8. Pfeiffer, R. A. and Kosenow, W.: Thalidomide and congenital abnormalities, Lancet 1:45 (Jan. 6)1962 b.
  9. Lenz, W.: Thalidomide and congenital anomalies, Lancet 1:45 (Jan. 6)1962.
  10. Jones, E. E. and Williamson, D. A. J.: Thalidomide and congenital abnormalities, Lancet 1:222 (Jan. 27) 1962.
  11. Lenz, W.: Thalidomide and congenital abnormalities, Lancet 1:271-272 (Feb. 3) 1962.
  12. Burley, D. M.: Thalidomide and congenital abnormalities, Lancet 1:271 (Feb. 3) 1962.
  13. Speirs, A. L.: Thalidomide and congenital abnormalities, Lancet 1:303-305 (Feb. 10) 1962.
  14. Kohler, H. G., Fisher, A. M., Dunn, P. M: Thalidomide and congenital abnormalities, Lancet 1:326 (Feb. 10) 1962.
  15. Willman, A., and Dumoulin, J. G.: Thalidomide ("Distaval") and foetal abnormalities, Brit. Med. Jour. 1:477 (Feb. 17) 1962.
  16. Devitt, R. E. F., and Kenny, S.: Thalidomide and congenital abnormalities, Lancet 1:430 (Feb. 24) 1962.
  17. Russell, C. S., and McKichan, M. D.: Thalidomide and congenital abnormalities, Lancet 1:429 (Feb. 24) 1962.
  18. Lenz, W.: Eintstehung von Missbildungen durch Medikamente, Arzt Mitt 47:494 (March 3)1962.
  19. Cretius, K., Fuchs, R.: "Mitteilung ueber die ungewoehnliche Haeufung von Mikround Amelia im Jahre 1961 and der niversitaets-Frauenklinik, Wuerzburg," Medizinische Klinik 1962 #21 (25 Maerz 1962).
  20. Oliver, Margaret: Thalidomide and congenital abnormalities, Lancet 1:542 (March 10) 1962.
  21. Hepp, Osker: Die Haufung der Angeborenen Defektmizbildungen der oberen Extremitaten. Med Klinik, 57:419-426 (Mar. 16) 1962. 22. Robertson, W.F.: Thalidomide ("Distaval") and Vitamin B. deficiency, Brit. Med. Jour. 1:792 (Mar. 17) 1962.
  22. Smithells, R. W.: Thalidomide and congenital deficiencies, Lancet 1:591 (Mar. 17) 1962.
  23. Morgan, B. C.: Thalidomide and foetal abnormalities, Brit. Med. Jour. 1:792 (Mar. 17) 1962.
  24. Stabler, F.: Thalidomide and congenital abnormalities, Lancet 1:591 (Mar. 17) 1962.
  25. Watson, G. I., Slater, B. C. S. and McDonald, J. C.: Maternal health and congenital deformity, Brit. Med. Jour. 1:793 (Mar. 17) 1962.
  26. Ferguson, A. W.: Thalidomide and congenital abnormalities, Lancet 1:691 (Mar. 31) 1962.
  27. Rogerson, G.: Thalidomide and congenital abnormalities, Lancet 1:691 (Mar. 31) 1962.
  28. Woodyatt, P. B.: Thalidomide, Lancet 1:750 (Apr. 7)1962.
  29. Rodin, A. E., Koller, L. A. and Taylor, J. D.: Association of Thalidomide (Kevadon) with congenital anomalies, Canad. Med. Ass. J. 86:744-746, April 21, 1962.
  30. Somers, G. F.: Thalidomide and congenital abnormalities, Lancet 1:912-913 (Apr. 28) 1962.
  31. Weicker, H., and Hungerland, H.: Thalidomid-Embryopathie, Deutsch Med Wschr, 87:992-1002 (May 11) 1962.
  32. Pliess, G.: Thalidomide and congenital abnormalities, Lancet 1:1128 (May 26) 1962.
  33. Cohen, Sidney: Thalidomide polyneuropathy, New England Jour. of Med. 24: (June 14) 1962.
  34. Lenz, W. and Knapp, K.: Die Thalidomid-Embryopathie, Deutsch Med Wschr, 84: 1232-1242 (June 15) 1962.
  35. Harris, E. L.: Detection of drug toxicity, Lancet 1:1305 (June 16) 1962.
  36. Smithells, R. W.: Thalidomide and malformations in Liverpool, Lancet 1:1270-1273 (June 16) 1962.
  37. Another Toxic Hazard, The New England Journal of Medicine, Vol. 266, No. 25 (June 21, 1962) (Editorial).
  38. Wigglesworth: Thalidomide ("Distaval") and foetal abnormalities, Brit. Med. Jour. 11:1758 (June 23) 1962.
  39. Quibell, E. P.: Thalidomide-damaged infants, Lancet 1:1402 (June 30) 1962.
  40. Taussig, Helen B.: A Study of the German Out-Break of Phocomelia, J.A.M.A. Vol. 180, No. 13 (June 30) 1962.
  41. Whatley, Elizabeth: Thalidomide-damaged babies, Lancet 11:46 (July 7)1962.
  42. Leck, I. M., and Miller, E. L.: Incidence of malformations since the introduction of Thalidomide, Brit. Med. Jour. 2:16-20 (July 7)1962.
  43. Spencer, K. E. V.: Thalidomide and congenital abnormalities, Lancet 11:100 (July 14) 1962.
  44. Kajii, Tadashi: Thalidomide and congenital deformit, Lancet 11:151 (July 21) 1962.
  45. Woollam, D. H. M.: Thalidomide disaster considered as an experiment in mammalian teratology, Brit. Med. Jour., 11:236-237 (July 28) 1962.
  46. Franklin, A. W., Rattenbury, G., Herford, M., Nettell, A.: Thalidomide-damaged infants, The Lancet II, 195 (July 28) 1962.
  47. Taussig, Helen B.: The Thalidomide syndrome, Scientific American, Vol. 207, No. 2, August 1962.
  48. Knapp, V., Christie, G. A., Seller, M.: Thalidomide and congenital abnormalities, The Lancet, II 249 (August 4)1962.
  49. Glick, E. N., Giroud, A., Tuchmann-Duplessis, H., Mercier-Parot, I.: Thalidomide and congenital abnormalities, The Lancet, II (August 11)1962.
  50. Woollam, H. M., Green, A., Jacobs J., Johnson, H. D.: Drugs and fatal abnormalities, Brit. Med. Jour. (August 11)1962.
  51. Carter, M. P., Wilson, F.: Tetracycline and congenital limb abnormalities, Brit. Med. Jour. (August 11) 1962.
  52. Thalidomide babies, The Lancet, II, 306 (August 11)1962.
  53. Wiggleworth, R.: Thalidomide damaged infants, The Lancet, II, 349 (August 18) 1962.
  54. The many names for Thalidomide, J.A.M.A., Vol. 18, No. 7 (August 18) 1962 (Editorial).
  55. Toms, D. A., Hunter, T. A. A., Ashley, D. J. B., Woollam, D. H. M., Applebey, M.: Thalidomide and congenital abnormalities, The Lancet, II, 300 (August 25) 1962.
  56. The Thalidomide story, Jour. of the Amer. PharmaceuticalAssn., (September) 1962.
  57. Mitscherlich, A. and Mielke, F.: The Death Doctors, Translated from the German by James Cleugh, London, Elek Books, 1962.


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