Embryology · Teratology and prenatal diagnosis

Isotretinoin and other retinoids !

Teratogen

Vitamin A–derived medicines for severe acne and psoriasis cause serious defects of the embryo's face, heart and brain.

Updated 2026-11-01

See it in 3D: Auricle · Mandible · Thymus · Pulmonary trunk · Ascending aorta

What it is

Isotretinoin (13-cis-retinoic acid) and other oral retinoids are among the most potent teratogens known. Retinoic acid is a normal embryonic signal that sets the position of Hox genes; in excess it disrupts the cranial neural crest and the pharyngeal arches. They therefore cause a characteristic embryopathy of the ear, jaw, thymus, heart and nervous system, and their use requires strict pregnancy prevention programmes.

Key facts

Critical period: the first trimester, especially the early weeks of organogenesis.
Acitretin (psoriasis) persists in the body for a long time, so contraception continues long after stopping it.
Very high amounts of vitamin A are also teratogenic in animal models.
Topical retinoids are absorbed much less, though their potential is debated.
Exposure is also linked to preterm birth and early neonatal death.

Critical period and mechanism

Critical period: first trimester, during neural crest migration and pharyngeal arch formation.
Retinoic acid acts on nuclear receptors that regulate the Hox genes of the head-to-tail axis.
Excess shifts pharyngeal arch identity and causes death or abnormal migration of cranial neural crest.
The crest's derivatives are hit: external and middle ear, mandible, thymus, parathyroids and the outflow tract septum.

Prevention

Mandatory pregnancy prevention programme: pregnancy tests before, during and after treatment.
Two contraceptive methods from one month before until one month after finishing isotretinoin.
Treatment decisions are made with the treating professional.

Markers

Retinoic acid
Hox genes
Cranial neural crest

What it does to the embryo and fetus

Microtia or anotia, narrow ear canals, low-set ears.
Micrognathia, cleft palate, hypertelorism.
Tetralogy of Fallot, truncus arteriosus, interrupted aortic arch.
Thymic hypoplasia, hydrocephalus, microcephaly, cerebellar anomalies and neurodevelopmental problems.

Test yourself

Think of the answer, then tap the question to see it.

Why does isotretinoin cause defects resembling the 22q11.2 deletion?

It disrupts the cranial neural crest and pharyngeal arches and pouches, which give rise to the thymus, parathyroids and outflow tract septum.

What are three typical defects of isotretinoin embryopathy?

Microtia or anotia, micrognathia or cleft palate, conotruncal heart defects, thymic hypoplasia and hydrocephalus.

What does the isotretinoin pregnancy prevention programme require?

Negative pregnancy tests before starting and monthly, two contraceptive methods, and registration of prescriber, pharmacy and patient.

Add to my cards (3)

See it in 3D

The structures of Durgical's 3D anatomy where it is found.

← All of 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: Isotretinoin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); Teratogenic Medications (StatPearls Publishing (NCBI Bookshelf), 2024); 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.