Congenital Anomalies Of The Extremities, Nomenclature And The Thalidomide Episode

Chester A. Swinyard, M.D., Ph.D.

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 administration 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 sub-classifications 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 1 presents the pertinent clinical data and anatomical classification of their anomalous extremities. Fig. 1is 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.


Chester Swinyard is Director, Children's Division, Institute of Physical Medicine and Rehabilitation, New York University Medical Center

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. 
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. 
Hand or Foot Attached Directly to Trunk. 
Hand or Forearm, or Foot and Leg, Attached Directly to Trunk. 
Hand or Foot Attached Directly to Arm or Thigh.