--- module: 086-03 language: en chapter: 86 title: "Organogenesis, Congenital Anomalies, and Teratology" module_title: "Nervous-system, craniofacial, sensory-organ development, and principles of teratology" source_sha256: 4c2b64bea339001ba36a6f4f2326564955aae3461b832fb47ff0b4be0fb18137 --- # Neural, craniofacial, and sensory development and teratology ## Brain vesicles and forebrain ### Neural tube closes from cervical region ### Three primary brain vesicles #### Prosencephalon: telencephalon and diencephalon #### Rhombencephalon: metencephalon and myelencephalon ### Cavities become the ventricles ### Hemispheres smooth, later gyri and sulci ### Commissures cross lamina terminalis #### Anterior, hippocampal, then corpus callosum ### Optic vesicles: retina is central tissue ### Pituitary: diencephalon plus Rathke pouch #### Remnants form cysts or tumours ## Brainstem and cerebellum ### Midbrain: alar tectum, basal motor structures ### Pontine flexure opens fourth ventricle roof #### Alar plates displaced lateral to basal #### Sensory nuclei lateral to motor nuclei ### Cerebellar plates from rhombic lips ### Roof plate becomes choroid plexus ### Aqueduct or outlet obstruction: hydrocephalus ## Spinal cord and neurons ### Mantle layer grey, marginal layer white ### Alar dorsal sensory, basal ventral motor ### Neural crest: ganglia and Schwann cells ### Column outgrows cord, cauda equina forms #### Tethering causes traction with growth ### Radial glia guide inside-out migration ### Interneurons migrate tangentially ### Myelination, pruning, critical periods ## Face and palate ### Frontonasal, maxillary, mandibular prominences ### Nasal placodes invaginate into pits ### Maxillary plus medial nasal: lip, primary palate #### Fusion failure: cleft lip ### Palatal shelves grow, elevate, fuse #### Failure at any step: cleft palate ## Tongue, thyroid, and skull ### Tongue from several arch swellings #### Anterior: first arch, taste via chorda tympani #### Posterior: third arch, glossopharyngeal #### Muscles: occipital myoblasts, hypoglossal ### Thyroid descends via thyroglossal duct #### Midline cyst moves with swallowing #### Ectopic tissue along the route ### Parathyroids and thymus from pouches ### Membranous bones, sutures, fontanelles ### Premature suture fusion #### Restricts growth perpendicular to suture ## Eye ### Optic vesicle induces lens placode ### Optic cup: pigment epithelium, neural retina ### Choroidal fissure must close #### Failure causes coloboma ### Cornea: surface ectoderm and neural crest ### Lens fibres elongate and lose nuclei ## Ear ### Otic placode invaginates into otic vesicle #### Cochlear duct, utricle, saccule, canals ### First pouch: middle ear and auditory tube ### Ossicles from first and second arches ### Auricle from six hillocks ### Ear anomalies may signal linked conditions #### Isolated minor variants often benign ## Teratogen principles and timing ### Dose, timing, metabolism, placenta, genotype ### Untreated maternal disease may harm more ### Preimplantation: loss or compensation ### Weeks three to eight: major malformations ### Later: growth, maturation, brain function ## Specific exposures and causation ### Alcohol: no proven safe threshold ### Retinoids disrupt neural-crest structures ### Valproate risk versus seizure control ### Infection: destruction, inflammation, vessels ### Maternal antibodies cross late in gestation ### Folate modifies neural-tube risk ### Causation: phenotype, timing, dose response ## Counselling and prevention ### Absolute versus relative risk ### Abrupt stopping can be dangerous ### Preconception control, folate, vaccination ### Link lineage, event, and time window