FIG 2 - uploaded by James F Cullen
Content may be subject to copyright.
-Case 2, close-up view of face showing small orbit on left side associated with microphthalmos. FIG. I .-Case 2, showing typical limb deformities in a thalidomide baby.
Source publication
Context in source publication
Context 1
... left orbit seemed underdeveloped compared to the right (Fig. 2), and the left eye was ex- tremely small with a corneal diameter of 4-5 mm. There was a large colobomatous defect in the iris below, involving one-third of its circumference, and it was not possible to get any view of the fundus. The child died from an intercurrent broncho-pneumonia at the age of 16 months, and post mortem examination ...
Citations
... Patients' profiles 20 year male with single digit in hands and feet presented to our opd, with his relatives having similar deformity of single toes and finger presented to our OPD, in KCGMCH, KARNAL, showing a unique congenital deformity of hands and feet with one opposing digit (monodactyly) on each hand [ Figure 2] and one opposing toe present in each foot. There were similar deformities reported from surrounding villages and adjoining area. ...
... However, thalidomide is still prescribed for the treatment of diseases such as leprosy, Crohn's disease, and multiple myeloma using schemes like System for Thalidomide Education and Prescribing Safety Program for monitoring patients who are not pregnant while receiving the medication. [17][18][19][20] It should be noted that thalidomide is not a mutagen and therefore is not associated with genetic transmission of deformities. [21] Familial inheritance ...
Background and Purpose
Congenital deformities occur due to abnormal development of limbs in the intrauterine life. The exact cause of this type of defect is not known but can be associated with environmental factors (drug history or exposure of chemical effluents from factory) or genetic predisposition. Cases involving the occurrence of single digits in all four limbs were witnessed, and the aim was to study and trace the cause of such deformities. Knowledge of thalidomide induced phocomelia which has already being published in the literature also contributed to our knowledge and understanding.
Objectives
(1) Primary objective was to identify the causative agent or genetic factor for the occurrence of single digits in hands and feet in multiple families. (2) Secondary objective was to create awareness among patients and the general public as well as local government authorities regarding such families of “Divyang” patients. We present a case series of multiple families with complete absence of all fingers and toes except one across villages in Haryana.
Materials and Methods
Clinical setting: (1) Study was based on a detailed questionnaire which was taken from multiple villagers (Tarawari Village, Nilokheri Village, etc.) and (2) phenotypic examination. Five affected patients from multiple families for 1 year were taken for study from March 2022 to March 2023. Their habitus, lifestyle, and environmental status were all studied and compared with other studies. Efforts were taken to study the license and toxic effluent treatment plan of a chemical factory present in the near vicinity.
Results
A strong genetic association was suggested for the occurrence of single digits in the hands and feet of multiple patients across multiple villages close to a chemical factory. They have well adjusted with writing, eating, riding bikes, and four-wheelers with single fingers and toes.
Conclusion
There is a need to establish genetic analysis so that the cause of such deformities could be known and prevented. There is also a need for general and government awareness toward pollutants released from chemical factories and their effects.
... It is theorized to cause teratogenic damage by disrupting embryonic angiogenesis and can affect a wide array of organs and tissues in the body [58]. In the UK, reported ocular malformations of thalidomide embryopathy encompassed colobomas, external ophthalmoplegia, anophthalmos, and microphthalmos [60,61]. One study in Sweden reported incomitant strabismus as the most common ocular anomaly, followed by aberrant lacrimation [59]. ...
The intricate steps of human ocular embryology are impacted by cellular and genetic signaling pathways and a myriad of external elements that can affect pregnancy, such as environmental, metabolic, hormonal factors, medications, and intrauterine infections. This review focuses on presenting some of these factors to recognize the multifactorial nature of ocular development and highlight their clinical significance. This review is based on English-language articles sourced from PubMed, Web of Science, and Google Scholar; keywords searched included “ocular development in pregnancy,” “ocular embryology,” “maternal nutrition,” “ophthalmic change,” and “visual system development.” While some animal models show the disruption of ocular embryology from these external factors, there are limited post-birth assessments in human studies. Much remains unknown about the precise mechanisms of how these external factors can disrupt normal ocular development in utero, and more significant research is needed to understand the pathophysiology of these disruptive effects further. Findings in this review emphasize the importance of additional research in understanding the dynamic association between factors impacting gestation and neonatal ocular development, particularly in the setting of limited resources.
... The second most common group of defects in thalidomidedamaged children/adults are seen in the eyes and ears (Miller and Stromland, 1999;Newman, 1985;Smithells, 1973;Smithells and Newman, 1992;Vargesson, 2009). Eye defects include cataracts, microphthalmos (congenital small eye), anophthalmos (absence of eyeball), poor vision, aberrant lacrimation problems, and, most commonly, colobomas (deformity of the iris and retina) (Cullen, 1964;Newman, 1985). Ocular defects usually occur unilaterally, although there may still be poor vision in the unaffected eye (Smithells, 1973). ...
Thalidomide is responsible for the biggest medical disaster in history, causing severe birth defects in more than 10,000 children, globally, between 1957 and 1962. Understanding how thalidomide caused birth defects has remained a challenge for many years. Yet thalidomide is now used around the world to successfully treat a wide range of conditions, including leprosy, Crohn's disease, multiple myeloma, and some cancers. Tragically, however, with its renewed use children are again being born with thalidomide-induced deformities, particularly in Brazil. Breakthroughs in the understanding of thalidomide's teratogenic actions raise the possibility of producing analogs or synthesizing new forms of thalidomide that maintain the clinical benefits but without the teratogenic side effects.
... 7 The prevalence of ocular deficits in humans has been reported to be 25% which majorly includes coloboma. 8 The effects of thalidomide exposure on a developing embryo revolutionized drug toxicological testing. 9 The anti-angiogenic property of thalidomide has been shown to be responsible for the adverse effects on development. ...
Since the conception of thalidomide as a teratogen approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. In this study, we challenged the developing embryo at the stage of blood island formations (HH8) which is the most vulnerable stage for thalidomide-induced deformities. We observed that thalidomide affects the early vasculogenesis through interfering with the blood island formation and extends its effect to organogenesis. The transcriptome analyses of the embryos collected on 6th day of incubation have shown that eye, liver and blood tissue associated genes are down regulated due to thalidomide treatment. The conserved gene co-expression module also indicated that the genes involved in lens development are heavily affected. Further, the Gene Ontology (GO) analysis explored that the pathways of eye development, retinol metabolism, and cartilage development are dampened in consistent with the observed deformities of eye (absence of lens formations) and other organs. The study concludes that thalidomide exerts its toxic teratogenic effects through interfering with early extra-embryonic vasculogenesis and ultimately gives an erroneous transcriptomic pattern to organogenesis.
... The second most common group of defects in thalidomide-damaged children/adults are seen in the eyes and ears (Miller and Stromland, 1999;Newman, 1985;Smithells, 1973;Smithells and Newman, 1992;Vargesson, 2009). Eye defects include cataracts, microphthalmos (congenital small eye), anophthalmos (absence of eyeball), poor vision, aberrant lacrimation problems, and, most commonly, colobomas (deformity of the iris and retina) (Cullen, 1964;Newman, 1985). Ocular defects usually occur unilaterally, although there may still be poor vision in the unaffected eye (Smithells, 1973). ...
Thalidomide is responsible for the biggest medical disaster in history, causing severe birth defects in more than 10,000 children, globally, between 1957 and 1962. Understanding how thalidomide caused birth defects has remained a challenge for many years. Yet thalidomide is now used around the world to successfully treat a wide range of conditions, including leprosy, Crohn's disease, multiple myeloma, and some cancers. Tragically, however, with its renewed use children are again being born with thalidomide-induced deformities, particularly in Brazil. Breakthroughs in the understanding of thalidomide's teratogenic actions raise the possibility of producing analogs or synthesizing new forms of thalidomide that maintain the clinical benefits but without the teratogenic side effects.
... DAR-4M-AM, 3 0 ,6 0 -Bis(dimethylamino)-9-[2-acetomethoxy carbonyl-3-amino-4-(N-methylamino) phenyl]xanthylium iodide; DAF-FM, 4-Amino-5-Methylamino-2 0 ,7 0 -Difluorofluorescein Diacetate; cPTIO, Carboxy-PTIO potassium salt; YC 1, 3-(5 0 -Hydroxymethyl-2 0 -furyl)-1-benzyl indazole; SpNO, Spermine NONOate; L-NAME, L-NG-Nitroarginine Methyl Ester; SQRT-PCR, Semiquantitative RT-PCR; SC, Sildenafil citrate; NO, Nitric oxide; DMEM, Dulbecco's modified Eagle's medium; PBS, Phosphate-buffered saline; ON, Optic Nerve. [3]. These eye defects included anophthalmia, microphthalmia, ophthalmoplegia and coloboma. ...
Thalidomide, the notorious teratogen is known to cause various developmental abnormalities, among which a range of eye deformations are very common. From the clinical point of view, it is necessary to pinpoint the mechanisms of teratogens that tune thegene expression. However, to our knowledge, the molecular basis of eyedeformities under thalidomide treatmenthas not been reported so far. Present study focuses on the possible mechanism by which thalidomide affects eye development andthe role of Nitric Oxide in recovering thalidomide-mediated anomalies of eye development using chick embryo and zebrafish models with transcriptome analysis. Transcriptome analysis showed that 403 genes were up-regulated and 223 genes were down-regulated significantly in thalidomide pre-treated embryos. 8% of the significantly modulated genes have been implicated in eye development including Pax6, OTX2, Dkk1 and Shh. A wide range of biological process and molecular function was affected by thalidomide exposure. Biological Processes including structural constituent of eye lens and Molecular functions such as visual perception and retinal metabolic process formed strong annotation clustersindicating the adverse effects of thalidomide on eye development and function. Here, we have discussed the whole embryo transcriptome with the expressionof PAX6, SOX2, and CRYAAgenes from developing eyes. Our experimental data showing structural and functional aspects includingeye size, lens transparency and optic nerve activity and bioinformatics analyses of transcriptome suggest that NO could partially protect thalidomide treated embryos from its devastating effects on eye development and function.
... Thalidomide can cause small eyes (micropthalmia), anophthalmos (absence of the eyeball), and poor vision. Eye defects also include aberrant or no lacrimation (tear formation), coloboma, and strabismus (Smithells, 1962;Cullen, 1964;James, 1965;Newman, 1977;Schmidt and Salzano, 1980;Kelsey, 1988;Miller and Stromland, 2011). Ocular defects can occur unilaterally, although there may still be poor vision in the unaffected eye (Smithells, 1962). ...
Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man-made medical disaster ever, where over 10,000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of adult conditions, including multiple myeloma and complications of leprosy. Tragically, a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects in the forming embryo remains unclear. However, studies in the past few years have greatly enhanced our understanding of the molecular mechanisms the drug. This review will look at the history of the drug, and the range and type of damage the drug caused, and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed. Birth Defects Research (Part C), 2015. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
... Thalidomide can cause small eyes (microphthalmia) anophthalmos (absence of the eyeball) and poor vision. Eye defects also include aberrant lacrimation (tear formation), coloboma and strabismus [7,14,17,20,25,45,58]. Ocular defects can occur unilaterally although there may still be poor vision in the unaffected eye [17]. ...
Thalidomide remains one of the world’s most notorious drugs due to the severe birth defects it induced in children between 1957 and 1962. Yet, to some this drug is a lifesaver, as it now enjoys renaissance in the treatment for a wide range of conditions including leprosy, multiple myeloma, Behcet’s disease, and some cancers. However, thalidomide has also been linked to causing a new generation of thalidomide survivors in Brazil, where the drug is used to treat leprosy. Surprisingly how thalidomide causes birth defects and how it acts in the treatment of clinical conditions are still far from clear. In the past decade great strides in our understanding of the actions of the drug, as well as molecular targets, have been made. The purpose of this review is to look at the recent work carried out into understanding how thalidomide causes birth defects, it’s molecular targets and the challenges that remain to be elucidated. These challenges include identifying clinically relevant but nonteratogenic forms of the drug, and the mechanisms underlying phocomelia and species specificity.
... The second commonest group of defects in thalidomide damaged children/adults is seen in the eyes and ears (Miller and Strömland, 1999;Newman, 1985;Smithells, 1973;Smithells and Newman, 1992;Vargesson, 2009). Eye defects include cataracts, microphthalmos (congenital small eye), anophthalmos (absence of eyeball), poor vision, aberrant lacrimation problems and, most commonly, colobomas (deformity of the iris and retina) (Cullen, 1964;Newman, 1985). Ocular defects usually occur unilaterally although there may still be poor vision in the unaffected eye (Smithells, 1973). ...
This chapter discusses thalidomide, a sedative-hypnotic and multiple myeloma medication, which is used to treat morning sickness in pregnancy, remains one of the most notorious and feared drugs in the world. This drug caused tissue damage, which resulted in limb deformities, but also affected ear, eye, heart, kidney, nerves, genitals and other internal organs. It gives us some idea about the history of this drug and its cause and effects on us today. These drugs adversely affect the internal organs such as heart, kidney, genitals and bowels. It is viewed that majority of birth defects in newborn children between 1957 and 1962 were due to the effects of this drug as it is used by the mother in the early stages of pregnancy, which is the time-sensitive period. Most of the thalidomide survivors suffer from limb deformity, both upper and lower. It also affects the eyes and ears a great deal. Internal organ deficit, nerve and central nervous system (CNS) deficit also constitute a major part. The most striking and defining characteristic of thalidomide embryopathy are the phocomelic limbs of survivors, which is defined as the loss of or severe shortening of the long bones of the limb. The risk assessment and toxicity are covered in an effective manner, which gives us an accurate idea about this drug. It concludes that the rising use of thalidomide around the world for the successful treatment of a large range of clinical conditions remains a risk as the drug causes adverse side effects to long-term adult users.
... The second commonest group of defects in thalidomide damaged children/adults is seen in the eyes and ears (Miller and Strömland, 1999;Newman, 1985;Smithells, 1973;Smithells and Newman, 1992;Vargesson, 2009). Eye defects include cataracts, microphthalmos (congenital small eye), anophthalmos (absence of eyeball), poor vision, aberrant lacrimation problems and, most commonly, colobomas (deformity of the iris and retina) (Cullen, 1964;Newman, 1985). Ocular defects usually occur unilaterally although there may still be poor vision in the unaffected eye (Smithells, 1973). ...
