[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Embryology](https://durgical.com/en/embryology/) › [Teratology and prenatal diagnosis](https://durgical.com/en/embryology/#a-teratology) › Thalidomide and limb reduction defects [Embryology](https://durgical.com/en/embryology/) · [Teratology and prenatal diagnosis](https://durgical.com/en/embryology/#a-teratology) # Thalidomide and limb reduction defects - Teratogen A 1950s sedative that left thousands of babies with very short arms and legs and changed drug safety for good. Updated 2026-11-01 **See it in 3D:** [Humerus](https://durgical.com/en/anatomy/humerus/) · [Radius](https://durgical.com/en/anatomy/radius/) · [Ulna](https://durgical.com/en/anatomy/ulna/) · [Auricle](https://durgical.com/en/anatomy/auricle/) · [1st metacarpal](https://durgical.com/en/anatomy/1st-metacarpal/) ## Key points - Narrow critical window: days 20 to 36 after fertilization (days 34 to 50 after the last menstrual period). - Phocomelia: hands or feet attached almost directly to the trunk; also amelia and radial dysplasia, mostly in the upper limbs. - Early exposure within the window: limbs, face, genitals and kidneys; late: digits, eyes and ears. - Other defects: ear (anotia, microtia, deafness), eye, heart, kidney and gut atresias. - Current use: complications of leprosy and multiple myeloma, with strict pregnancy prevention. ## What it is Thalidomide was used in the late 1950s for anxiety and morning sickness, and between 1957 and 1962 more than 10,000 children were born with severe defects. Its best-known effect is phocomelia, but it also damages the ears, eyes, heart, kidneys and gut. Its story showed that drugs cross the placenta and founded modern teratology; today it is used under strict pregnancy prevention programmes. ## Key facts - It binds cereblon, part of a complex that tags proteins for degradation. - Other hypotheses: inhibition of blood vessel formation (anti-angiogenesis) and oxidative stress. - The link was found because phocomelia was a very rare defect; a common defect would have gone unnoticed. - No safe exposure time in pregnancy has been established. - Amelia is total absence of a limb; meromelia, partial absence. ## Critical period and mechanism - Critical period: days 20 to 36 after fertilization, while the limb buds grow. - Binding cereblon disturbs the degradation of developmental regulatory proteins. - Blocking new vessels in the limb bud causes cell death and loss of signalling between the apical ectodermal ridge and the mesenchyme. - Proximal segments form first; if their cells die, the hand or foot ends up attached to the trunk. ## Prevention - Mandatory pregnancy prevention programmes for anyone receiving thalidomide or related drugs. - Pregnancy tests and effective contraception before, during and after treatment. - Treatment decisions are made with the treating professional. ## What it does to the embryo and fetus - Phocomelia, amelia, radial dysplasia and absent thumb. - Anotia or microtia with deafness; coloboma and microphthalmia. - Heart defects, renal and genital anomalies, intestinal atresias. - Facial haemangioma and cranial nerve palsies. ## Memory aid Thalidomide 'shortens from the shoulder': between days 20 and 36 the upper segments are lost and the hand sits on the trunk. ## Test yourself Think of the answer, then tap the question to see it. ## What is thalidomide's critical window? Days 20 to 36 after fertilization, equivalent to days 34 to 50 after the last menstrual period. ## What is phocomelia? A reduction defect in which the long bones are missing and the hand or foot is attached almost directly to the trunk. ## What is thalidomide used for today? Complications of leprosy and multiple myeloma, under strict pregnancy prevention programmes. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/embryology/thalidomide-and-limb-reduction-defects/) ## See it in 3D The structures of Durgical's 3D anatomy where it is found. - [Humerus](https://durgical.com/en/anatomy/humerus/) - [Radius](https://durgical.com/en/anatomy/radius/) - [Ulna](https://durgical.com/en/anatomy/ulna/) - [Auricle](https://durgical.com/en/anatomy/auricle/) - [1st metacarpal](https://durgical.com/en/anatomy/1st-metacarpal/) ## Related - [Limb development: the apical ectodermal ridge, ZPA and limb rotation](https://durgical.com/en/embryology/limb-development-the-apical-ectodermal-ridge-zpa-and-limb-rotation/) - [Limb defects: amelia, meromelia, polydactyly and syndactyly](https://durgical.com/en/embryology/limb-defects-amelia-meromelia-polydactyly-and-syndactyly/) - [Principles of teratology: critical periods, dose and genotype](https://durgical.com/en/embryology/principles-of-teratology-critical-periods-dose-and-genotype/) - [Congenital hearing loss, microtia and preauricular pits](https://durgical.com/en/embryology/congenital-hearing-loss-microtia-and-preauricular-pits/) - [Coloboma, congenital cataract and congenital glaucoma](https://durgical.com/en/embryology/coloboma-congenital-cataract-and-congenital-glaucoma/) - [Molecular regulation: Shh, Wnt, FGF, BMP, Hox genes and retinoic acid](https://durgical.com/en/embryology/molecular-regulation-shh-wnt-fgf-bmp-hox-genes-and-retinoic-acid/) ## Related conditions - [Multiple myeloma](https://durgical.com/en/conditions/multiple-myeloma/) [← All of embryology](https://durgical.com/en/embryology/) Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given. Sources: [Thalidomide‐induced teratogenesis: History and mechanisms](https://pmc.ncbi.nlm.nih.gov/articles/PMC4737249/) (Birth Defects Research Part C (PubMed Central), 2015); Langman's Medical Embryology, 13th ed., ch. 9: Birth Defects and Prenatal Diagnosis (Wolters Kluwer, 2015). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/embryology/thalidomide-and-limb-reduction-defects/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/embryology/thalidomide-and-limb-reduction-defects/