Thalidomide and Congenital Abnormalities

Toms, D. A.; Hunter, T.; Ashley, David J. B.; Woollam, D. H. M.; Applebey, Mary

doi:10.1016/s0140-6736(62)90252-0

Cited by 12 publications

(3 citation statements)

References 3 publications

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“…In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative 1 , 2 . This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation 3 - 5 .…”

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confidence: 99%

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning

Galloway

Delgado

Ros

et al. 2009

Nature

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Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3-5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the Progress Zone Model, which states that a cell’s proximodistal (PD) identity is determined by the length of time spent in a distal limb region termed the “Progress Zone” 7. Indeed, studies of X-irradiation induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the Progress Zone Model. Here, using a combination of molecular analysis and lineage tracing, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. As skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the etiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that PD patterning is unaffected following X-irradiation does not support the predictions of the Progress Zone Model.

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confidence: 99%

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning

Galloway

Delgado

Ros

et al. 2009

Nature

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“…After the use of this drug was restricted, there was a decrease in the number of phocomelia cases. 5,6 In additon to tolidomide, alcohol, cyclophosphamide and reti noic acid have been implicated in the pathogenesis. İn studies, phocomelia has been reported after use of retinoic acid in pregnant mice.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Diagnosis of Sporadic Phocomelia Associated with Diaphragmatic Hernia: A Case Report

Cömert¹,

Şal²,

Ekici³

et al. 2018

TJRMS

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Phocomelia is a rare conjenital anomaly and seen in 4 million births. Many factors play a role in etiology of phocomelia such as environmental-genetic factors, teratogen exposure, amniotic band syndrome, thalidomide and also alcohol, cyclophosphamide and retinoic acid have been implicated in the pathogenesis. Phocomelia may be isolated or accompained by syndromes. A 35-years-old woman was admitted to our clinic for detailed ultrasonographic examination. Absence of some extremities and congenital diaphragmatic hernia was observed. There was no factors for phocomelia in family because of that, we suggested this case may be isolated. In this case, we present a case of isolated sporadic phocomelia with diaphragmatic hernia that was diagnosed and defined in our clinic. K Ke ey yw wo or rd ds s: : Diaphragmatic hernia; phocomelia; prenataly; sporadic; termination Ö ÖZ ZE ET T Fokomeli, 4milyon doğumda bir görülen etiyolojisinde pek çok etkenin rol oynadığı nadir bir hastalıktır. Fokomeli etiyolojisinde çevreselgenetik faktörler, teratojen maruziyeti, amniyotik band sendromu gibi faktörler yer alabildiği gibi, izole olarak da gözlenebilmektedir. Talidomid dışında alkol, siklofosfamid ve retinoik asitte patogenezinde suçlanmıştır. Fokomeli izole olabileceği gibi Robert-SC fokomeli, Furhmann sendromu, Al-Awadi/Roos-Rthschild/Schinzel fokomeli gibi bazı sendromların parçası olabilir. 35 yaşında bir kadın ayrıntılı ultrasonografik inceleme için kliniğimize başvurdu.Sağ alt ekstemite total olarak sol ekstremitede ise distal kısım yokluğuna ek olarak diyafragma hernisi gözlenmiştir. Ailede fokomeli için hiçbir risk faktörü yoktu, bu yüzden bu vakanın izole olabileceğini öne sürdük. Sunduğumuz bu olguda kliniğimizde tanı ve teşhis edilen diyafragma hernisine ek olarak eşlik eden izole sporadik fokomeli olgusunu sunmak istedik.

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“…[26] Its subsequent use for the treatment of morning sickness among pregnant women was linked to an increase in limb defects among newborns with an estimated 10,000 cases of birth defects worldwide. [27] As such, there remains a demand for hESC based teratogenic testing systems, allowing for improved prediction of teratogenicity.…”

Section: The Use Of Human Embryonic Stem Cell Assaysmentioning

confidence: 99%

In Vitro Microscale Models for Embryogenesis

Rico-Varela

Wan

2018

Adv. Biosys.

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Embryogenesis is a highly regulated developmental process requiring complex mechanical and biochemical microenvironments to give rise to a fully developed and functional embryo. Significant efforts have been taken to recapitulate specific features of embryogenesis by presenting the cells with developmentally relevant signals. The outcomes, however, are limited partly due to the complexity of this biological process. Microtechnologies such as micropatterned and microfluidic systems, along with new emerging embryonic stem cell-based models, could potentially serve as powerful tools to study embryogenesis. The aim of this article is to review major studies involving the culturing of pluripotent stem cells using different geometrical patterns, microfluidic platforms, and embryo/embryoid body-on-a-chip modalities. Indeed, new research opportunities have emerged for establishing in vitro culture for studying human embryogenesis and for high-throughput pharmacological testing platforms and disease models to prevent defects in early stages of human development.

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Thalidomide and Congenital Abnormalities

Cited by 12 publications

References 3 publications

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning

Prenatal Diagnosis of Sporadic Phocomelia Associated with Diaphragmatic Hernia: A Case Report

In Vitro Microscale Models for Embryogenesis

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