Nel 1957 accadde un gravissimo incidente ad un rettore nucleare a Windscale (Sellafield) che provocò in Inghilterra l'emergenza nazionale. La contaminazione era rilevabile in tutta europa. Nello stesso anno nella città segreta di Mayak, Kyshtym, nella oggi ex-URSS, esplose una discarica di materiale nucleare. Entrambi gli incidenti vennero tenuti segreti per decenni. Era il periodo in cui i laboratori di ricerca della famosa multinazionale Monsanto proponevano una nuova macchinetta per fare il caffè alimentata da plutonio, la cui ricarica sarebbe durata 100 anni. [H. Peter Metzger, The Atomic Establishment (New York: Simon & Schuster, 1972). ISBN 671-21351-2., pag. 227]. In totale, secondo l'editorialista del "New York Times" H. Peter Metzger, l'Atomic Energy Commission americana bruciò miliardi di dollari di tasse dei cittadini in progetti idioti al solo scopo di dimostrare che la tecnologia nucleare era benefica ed, ovviamente, in alcun modo pericolosa. In questo periodo di massima contaminazione (sia in senzo fisico che mentale), dovuta in gran parte ai test nucleari atmosferici, spuntò la "malattia della Talidomide". Molti effetti attribuiti alla Talidomide sono facilmente riconducibili alla contaminazione in utero delle donne che all'epoca erano incinte. Oggi miliardi di dollari vengono spesi per propagandare il virus dell'AIDS affinché la gente non si chieda qual'è la vera origine della pandemia di immunodeficenza, ovvero la contaminazione dell'ambiente che i nuclearisti vorrebbero continuare impunemente all'infinito.

The second paradox is that, bearing in mind that 2 to 3% of all babies born have significant birth defects, and that thalidomide consumption was widespread in 1960 to 1961, some mothers who undoubtedly took the drug when pregnant (though probably outside the sensitive period) gave birth to babies with defects quite unrelated to thalidomide. It is also possible for a baby exposed to thalidomide during the sensitive period to be born with a variety of defects, of which some, but not all, are drug induced.

Cleft lip and palate

These occur among persons affected by thalidomide more often than in the general population. The deformities appear not to differ from other facial clefts.

Summary of external defects associated with thalidomide

Upper limbs
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).
Fingers: absence, hypoplasia, fixed flexion, syndactyly (preaxial emphasis).
Thumb: absence, hypoplasia, triphalangy, non-opposable.
Lower limbs
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).

Craniofacial

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.

Stature

Often short because of poor growth/osteochondritis of spine/progressive kyphosis.

External genitalia

Hypoplasia of scrotum/labia with severe lower limb deficiency.

FUNCTIONAL PROBLEMS

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.

A number of acquired diseases (for example, coeliac disease, diabetes, multiple sclerosis) have been seen, but no more frequently than expected by chance. A causal relationship is unlikely.

Differential diagnosis

LIMB DEFECTS

Some of the conditions which have caused problems in the past will not do so in the future because they are associated with perinatal or early childhood death. These include short limbed dwarfism, which should not present diagnostic difficulty (for example, achondrogenesis, thanatophoric dwarfism, severe ostiogenesis imperfecta), and pseudothalidomide syndrome (Roberts syndrome, SC syndrome), an autosomal recessive disorder which includes limb reduction deformities.

Life expectancy is more variable in the TAR (thrombocytopenia-absent radius) syndrome, an autosomal recessive disorder in which thrombocytopenia tends to improve and may not be evident after the neonatal period, and in which absent radii are associated with normal thumbs, and in the Cornelia de Lange syndrome, in which the limb defects are bizarre and asymmetrical, and other features often suggest the diagnosis at birth.

Radial aplasia is a feature of Fanconi’s panmyelopathy, but the blood changes indicate the diagnosis. The family history may indicate autosomal dominant radial aplasia (though not, of course, new mutations). Radial and external ear defects may be associated with deafness, eye, cardiac, and dental defects in the lacrimo-auriculo-dento-digital (LADD) syndrome. The maternal history will help to identify diabetic embryopathy (which does not closely resemble thalidomide embryopathy).

Amniotic band lesions most often affect a single limb, are rarely symmetrical, and resemble ‘congenital amputations’. Ring constrictions may be present on one or more limbs.

Poland anomaly is unilateral, the hand defect being associated with agenesis of part of the pectoralis major muscle. There may be homolateral deficiency of the breast, nipple, or ribs.

In the femur-fibula-ulna (FFU) syndrome, the named bones are principally affected, contrasting with thalidomide which affects the radius and humerus before the ulna, and the tibia before the fibula. The defects may be very asymmetrical.

The major difficulty is presented by the Holt-Oram syndrome, an autosomal dominant disorder usually affecting the hands and forearms symmetrically, and associated in almost all cases with congenital heart disease, principally atrial septal defect. The family history often helps, but new mutations occur.

EYES, EARS, ETC.

Five syndromes need to be considered here, one of which can cause considerable difficulty. Goldenhar syndrome (oculoauriculovertebral dysplasia), which merges with hemifacial microsomia, is characterised by microtia, accessory auricles, epibulbar dermoids, and abnormalities of the certical spine. Wildervanck syndrome (seen predominantly in girls) is characterised by malformed ears, deafness, and defects of the cervical spine. Thalidomide rarely affects the cervical spine. Möbius syndrome may manifest as facial/ocular palsies.

Duane syndrome is a disorder of ocular movements characterised by (1) decreased abduction, (2) decreased adduction, (3) retraction of the globe on adduction, (4) oblique rise or depression on adduction, (5) partial closure of the eyelids on adduction, (6) deficient convergence. It may be bilateral or unilateral. An association with other defects, especially of the hands and ears, was described as long ago as 1918. Some or all of these features, together with the Marcus Gunn ‘jaw winking’ phenomenon, occasionally accompany thalidomide facial defects.

The LADD syndrome has been considered above.

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.

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