Thalidomide is a teratogenic drug, meaning that when taken while pregnant, it can have terrible impacts on fetal development and cause irreversible damages.
Phocomelia, a limb atrophy, is the most common malformation linked to thalidomide, but all phocomelia cases aren’t caused by thalidomide. However, due to the notoriety of the thalidomide tragedy, many people have started to associate it exclusively with thalidomide. As a matter of fact, we often hear that persons with phocomelia are “like thalidomiders”, which gives the wrong impression that thalidomide is always involved.
Before considering thalidomide to be the cause of a malformation, regardless of the birth dates involved, people should consider other potential conditions. In fact, upon further investigation, we realize that many conditions have been mistakenly attributed to the drug. In some cases, certain experts might be able to tell the difference, but in others, it can be really hard.
The identification of birth defects attributable to thalidomide was a painful and confusing process. Some countries and pharmaceuticals have done better than others, but many of them could not verify that each petitioner was a true thalidomide victim.
According to Dr. Widukind Lenz, the malformations that we observe in thalidomiders are among the following:
Dr. Lenz continues:
“ Thalidomide may cause quite different malformations in different children. In one case, the ears are missing, there is deafness and paralysis of the muscles of the eyes and the face, but the limbs are normal. In another case, the ears are normal, but the arms are missing. In a third case there are severely shortened arms with only 2 or 3 fingers, often accompanied by internal malformations. In a fourth case, only the thumbs are abnormal with three joints, possibly accompanied by narrowing of the anus. ”
The type of malformations caused by thalidomide depends of the moment the drug was taken. Generally, thalidomide do not have any consequences if taken before the 34th or after the 50th day following the last menstruation. The period that goes from the 35th to the 50th day of pregnancy is critical, because it’s during that time that the fetus develops its limbs and organs.
Still according to Dr. Lenz, if thalidomide is taken during the critical period, the ears, arms, legs and organs can be severely damaged, which often leads to premature death. Given the severity of thalidomide impacts, almost 40% of thalidomide babies die before their first birthday.
The malformations linked to thalidomide are typical enough for an informed eye, but can easily be mistaken with birth defects resulting from other causes. Smithells and Newman wrote a detailed presentation of malformations attributable to thalidomide, of which the summary is presented below. It is relevant to note that when birth defects are the result of a teratogenic agent, the malformations are mostly symmetrical, since both sides of the human body develop simultaneously.
Shoulder: hypoplasia of shoulder muscles, scapula, clavicle.
Arm: total absence, prominent acromioclavicular joint.
Upper arm: reduction deformity of humerus (upper end).
Elbow: humeroulnar, radioulnar fusion.
Forearm: reduction deformities of radius>ulna.
Hand: deformities usually related to those of forearm (preaxial emphasis, for example, radial club hand).(accentuation préaxiale, main bote radiale).
Fingers: absence, hypoplasia, fixed flexion, syndactyly (preaxial emphasis).
Thumb: absence, hypoplasia, triphalangy, non-opposable.
Hip: congenital dislocation.
Thigh: reduction deformity of femur (upper end).
Knee: patellar dislocation.
Lower leg: reduction deformity of tibia > fibula.
Foot: deformities usually related to those of leg (for example, club foot).
Toes: polydactyly, bifid toes (preaxial emphasis).
Characteristic facies in some cases.
Central facial naevus, fading over one to two years.
Eyes: anophthalmia, microphthalmia, coloboma of iris/retina, conjunctival dermoid cyst.
Ears: anotia, microtia, accessory auricles; atresia, stenosis, tortuosity of external auditory meatus.
Neurology: facial palsy, restricted eye movements, tear-saliva syndrome.
Often short because of poor growth/osteochondritis of spine/progressive kyphosis.
Hypoplasia of scrotum/labia with severe lower limb deficiency.
A number of thalidomide damaged persons exhibit a variety of neurodevelopmental problems: mental handicap, dyslexia, autism, or epilepsy. These problems appear indistinguishable from the same conditions in people not affected by thalidomide, but they have occurred more often than would be expected by chance and have therefore generally been accepted as attributable to the drug when associated with more characteristic features.
Summary of internal defects associated with thalidomide
Heart: patent ductus arteriosus, VSD, ASD, and pulmonary stenosis in survivors. Complex, especially conotruncal, lesions were seen among early deaths.
Urinary tract: absent, horseshoe, ectopic, hypoplastic, rotated kidney; hydronephrosis, megaureter, ectopic ureter, vesicoureteric reflux, inert bladder.
Genital tract: undescended, small, or absent testis, hypospadias, cyst of hydatid of Morgagni; vaginal atresia, interruption of the Fallopian tube, bicornuate uterus.
Alimentary tract: duodenal atresia, pyloric stenosis, inguinal hernia, imperforate anus with fistula, anorectal stenosis, anteriorly displaced anus, (Congenital absence of appendix and gall bladder have been noted at necropsy.)
Orofacial: cleft palate, high arched palate, bifid uvula, palatal palsy, cleft lip, choanal atresia, small mandible, conjunctival dermoids; absent, overcrowded, or maloccluded teeth.
Skeletal: sacral agenesis, hemiverrabrae, rib anomalies.
Neurodevelopmental problems: mental handicap, epilepsy, dyslexia, receptive dysphasia, behaviour disorder (including autistic and hyperkinetic), involuntary movements. Some of these defects have been recorded only once or twice, and the association with thalidomide may be coincidental, but most of the defects listed have been seen more frequently than would be expected by chance.
For a more detailed and technical description of malformations attributable to thalidomide, we invite you to read the complete article written by Smithells and Newman.
What follows now is a list (with brief definitions) of some of the most common conditions mistaken for thalidomide malformations. The descriptions are, necessarily, very technical — making for dry reading, but it is important that the conditions be presented in this format to ensure that there is no misinterpretation. The article from Smithells and Newman discuss these differential diagnosis with more details.
To confuse the picture still further, medical publications contain examples of children who appear to show a mixture of features of more than one syndrome, for example Möbius syndrome and Poland anomaly. Whether these children are manifesting two separate syndromes, an entirely different syndrome, or some unusual ‘intermediate’ manifestation can only be a matter for speculation and further research.
There are many syndromes or conditions that exist and have finally been identified. With the ever-increasing developments in the field of genetics, many more will likely be known and better understood in the future. Providing this short list was intended to show that many of the ‘traits’ most commonly associated with thalidomide-related malformations can be found elsewhere either together or separately. It is often left to the patient to provide their doctor (geneticist) with the name of a condition to look up to start them in the right direction. Most important though, is having a CORRECT diagnosis to ensure correct treatment and reproduction information.