Thalidomide Did Not Cause All Birth Defects

THALIDOMIDE Did Not Cause All Birth Defects

by Randolph Warren, CEO August 16, 1999

With the rehabilitation of thalidomide (new use and licensing) and as a result, the attention given the drug and victims by the media, it becomes important to revisit the past and discuss just what is a thalidomide victim.

Identification of people’s disabilities resulting from the drug thalidomide was a tedious, confusing, and inconsistent process. Some countries and drug companies were better than others, but many failed to ensure that every claimant (person coming forward thinking they were a thalidomide victim) actually was.

Some mothers truly believed they had exposure to thalidomide during pregnancy -- they remembered taking a pill or being given something.-- Families faced with the shock of children being born with limb defects and/or other deformities, compounded with the media frenzy surrounding thalidomide, naturally, made a connection between the defects and the widely available drug. This just wasn’t always true. It is known "that 2 to 3% of all babies born have significant birth defects, and while 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."

Good evidence of misdiagnosis exists in the cases of those claiming to have second generation thalidomiders as offspring. This is just not possible, thalidomide deformities are not passed from generation to generation. These claimants have likely been born disabled due to factors other than thalidomide. In some cases their limb defects are remarkably thalidomide-like, but are not a result of thalidomide exposure.

In some cases, the fault regarding misdiagnosis of individuals as thalidomiders lies with scientists and doctors, and even the scientific knowledge of the day. The fact is that the field of genetics just wasn’t as progressed or sophisticated as today, and the coincidence of thalidomide availability and birth defects led to an assumption of cause, known to be wrong today. Moreover, many doctors with limited experience of thalidomide malformations are responsible for misdiagnoses. Patients born during thalidomide’s availability years, with limb defects of all sorts, were told by medical professionals that they were thalidomiders. Often these diagnoses were made from visual examinations by doctors not qualified to make those determinations. Even one limb missing or deformed could result in a diagnosis of "congenital malformations due to thalidomide" by physicians who did not possess all the tools or information necessary to make such determinations...

"Thalidomide caused a wide variety of birth defects, not one of which was unique to that drug. Nevertheless, the nature and pattern of the defects are, in most cases, characteristic enough to be recognizable to an experienced eye..."

"The last general point to mention is the risk of perpetuating an error. If a clinician accepts as resulting from thalidomide a defect which has not, in fact, been described in cases with strong documentary support, he is more ready to accept that defect the next time he meets it. A defect that has been accepted two or three times becomes built into his repertoire of ‘thalidomide defects’."

Another devastating component can be traced back to the greed of drug companies. When a family, convinced of their child’s thalidomide deformities and tenacious in their beliefs, approached the drug companies for compensation, the drug companies accepted their claims to avoid legal action. There were some parents of children with similar disabilities who lied about taking thalidomide, and the drug companies accepted them just to be rid of the problem.

With renewed attention regarding thalidomide and thalidomide victims (and therefore their malformations), there are many people coming forward making the assumption that thalidomide caused their birth defects. Sadly, media coverage is often incomplete or inaccurate, causing people to make assumptions based on false information. Well-meaning friends, family, and lay experts also compound this problem of misdiagnosis and misunderstanding by making lay observations, convincing vulnerable adults with disabilities that thalidomide is responsible for their situations, because of a show they saw ... an article they read or new memories of what happened. For many of these new claimants the drive to prove their thalidomide status comes from an imagined windfall in the form of compensation. Many are desperate financially, looking for a solution to that situation, and become passionate in their beliefs that thalidomide was the cause of their disability will be their salvation.

On a final note, another major difficulty in persons claiming to be born disabled as a consequence of the drug thalidomide, is that they assume thalidomide to be the cause first. In fact it should be considered only after genetic testing has been done to eliminate other potential causes.

Some Conditions Mistaken for Thalidomide Malformations

There are many conditions (genetic and otherwise) that can cause birth defects. In fact, phocomelia, the most common limb malformation associated with thalidomide has existed throughout history and continues to manifest itself to this day. It was only because of the thalidomide tragedy and the notoriety surrounding it, that phocomelia began to be associated for many, exclusively with thalidomide. People are now described as ‘thalidomide-like’ in relation to their disabilities, leading persons to believe thalidomide to be the cause.

Before considering thalidomide to be the cause of a disability regardless of the birth dates involved, people should consider other potential conditions. There are many "recognizable defects and syndromes which, to a greater or lesser degree, resemble thalidomide defects." In fact, upon further investigation, many conditions have been mistakenly attributed to the drug. "Some of these are unlikely to confuse an experienced eye; others can present considerable difficulty."

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. They are presented in no particular order.

ROBERTS-SC PHOCOMELIA (Pseudothalidomide syndrome, Roberts syndrome, SC syndrome) is an autosomal recessive disorder which includes limb reduction deformities. Some abnormalities associated with this syndrome include but are not limited to: cleft palate, malformed ears with hypoplastic lobules, various degrees of limb reduction, reduction in numbers or length of fingers and/or toes.

HOLT-ORAM SYNDROME also known as Heart Hand syndrome is 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. Some of the abnormalities noted with this syndrome include but are not limited to: phocomelia, all gradations of defect in the upper limb and shoulder girdle, and the thumbs may be absent, hypoplastic, triphalangeal, or bifid.

TAR SYNDROME (thrombocytopenia-absent radius) is an autosomal recessive disorder in which thrombocytopenia tends to improve and may not be evident after the neonatal period, and in which absent radii (bilateral) are associated with normal thumbs.Abnormalities in the legs are reported in 50% of the cases.

CORNELIA DE LANGE SYNDROME is a syndrome in which the limb defects are asymmetrical. Some other abnormalities associated with this syndrome include but are not limited to: phocomelia and oligodactyly, proximal implantation of thumbs, depressed nasal bridge, and undescended testes.

FANCONI’S PANMYELOPATHY includes radial aplasia as a feature, but the blood changes indicate the diagnosis. Some of the abnormalities associated with this condition include but are not limited to: short stature, hypoplasia to aplasia of thumb, small penis, and small testes.

LADD SYNDROME or lacrimo-auriculo-dento-digital syndrome results in radial and external ear defects which may be associated with deafness, eye, cardiac, and dental defects. Limb abnormalities that can be associated with this syndrome include but are not limited to: digitalization of thumb (95%), triphalangeal thumb, syndactyly between index and middle fingers, absent radius and thumb, and shortening of radius and ulna.

POLAND ANOMALY (Poland Sequence) is unilateral with 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. It is estimated that 10% of patients with syndactyly of the hand have Poland sequence, and it is 75% right-sided.

FFU SYNDROME (femur-fibula-ulna) is a syndrome in which 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.

GOLDENHAR SYNDROME (oculo-auriculo-vertebral dysplasia), which merges with hemifacial microsomia, is characterised by microtia, accessory auricles, epibulbar dermoids, and abnormalities of the certical spine.When unilateral this syndrome tends to be right-sided. Other abnormalities that are associated with this syndrome include but are not limited to: middle ear anomaly with variable deafness, cleft lip, and cleft palate.

WILDERVANCK SYNDROME (cervico-oculo-acoustic syndrome) is seen predominantly in girls and is characterised by malformed ears, deafness, and defects of the cervical spine. Thalidomide rarely affects the cervical spine. Cleft palate has also been identified as an occasional abnormality associated with this syndrome.

MÖBIUS SYNDROME (Moebius sequence) may manifest as facial/ocular palsies. It "is most commonly a sporadic occurrence in an otherwise normal family."

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.

VATER ASSOCIATION, "a nonrandom association of vertebral defects, imperforate anus, and esophageal atresia with tracheoesophageal fistula has long been appreciated." Some other abnormalities or defects include but are not limited to: thumb or radial hypoplasia, and defects of the lower limb (23%).

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. Amniotic band disruption sequence syndrome also has cleft lip and palate listed as an abnormality that can be associated with it. "Failure to understand the cause of this condition can lead to misdiagnosis and inappropriate family and genetic counselling."

"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.

Why is it so important to be accurate?

Every person has a right to know what caused their disability to the best extent scientifically possible. The very first thing that jumps out is that if their disabilities are genetic and/or generational, these persons with disabilities have the right to this knowledge for family planning. As well, if there is a larger than average population of persons born with disabilities not as a result of thalidomide, perhaps some other agent is responsible.

Moreover, problems and issues experienced by pseudo-thalidomiders or those wrongly diagnosed, may not pertain to actual thalidomide victims and this creates needless fear. As well, those misdiagnosed but accepted persons, could corrupt ongoing studies of thalidomiders.

With thalidomide licensed again, we must be sure that when an accident occurs, that it truly is a case of thalidomide causing the disability. If we ‘cry wolf’, no one will ever listen when the real ‘wolf’ shows up.

Doctors must seek and be given the tools to make proper determinations and referrals. Thalidomide malformations are not listed in the traditional medical reference books on birth defects used by physicians today. The truth about thalidomide-related malformations must be included in these reference materials and most particularly MUST be published in Smith’s Recognizable Patterns of Human Malformation. Thalidomide malformations must be included in the curriculum of Medical Schools, and published in Medical Journals.

Even today, physicians are making assumptions regarding what is or is not a thalidomide related malformation. The Thalidomide Victims Association of Canada receives daily inquiries from persons firmly and falsely convinced that thalidomide caused their defects.

There is no blood test to prove one is a thalidomide victim.

In a world and time with thalidomide available, we can no longer bury the facts.