Embryology

Question 1

Notochord role in neural development?

Answer 1

notochord induces overlying ectoderm to differentiate into neuroectoderm and form the neural plate → edges elevate to form folds and depresses for groove → fusion at 5th somite ~week 4

Question 2

What does the neural plate give rise to?

Answer 2

neural tube (brain and spinal cord) and neural crest cells.

Neural crest: PNS, ganglia, schwann cells, melanocytes, satellite cells, arachnoid & pia mater, merkel cells (pressure), cartilages of head and neck

Question 3

What does the notochord become in adults?

Answer 3

the nucleus pulpous of the intervertebral disc

Question 4

Alar vs basal plate?

Answer 4

Within intermediate layer (gray matter of spinal cord) neuroblasts develop into alar/basal separated by sulcus limitans

• Alar (dorsal) = sensory (2° afferent dorsal horn)
• Basal (ventral) = motor (efferent ventral horn, preganglionic sympathetic neurons)

Question 5

Cell layers in neural tube?

Answer 5

Ventricular: neuroepithelial neural canal → ependyma

Intermediate: neuroblasts (gray matter)→ alar/basal

Marginal: axons of neuroblasts (white matter)

Question 6

Three primary vesicles of developing brain?

Answer 6

Prosencephalon

telencephalon: Lateral ventricle

Cerebrum, insula, basal ganglia, corpus collosum, internal capsule, CN I

diencephalon: 3rd ventricle

thalamus, hypo-, epi-, CNII and retina, posterior pituitary, infundibulum

Mesencephalon

mesencephalon: midbrain, cerebral aqueduct

Rhombencephalon

metencephalon: pons, cerebellum, 4th ventricle
myelencephalon: medulla

Question 7

What does the neuroectoderm give rise to?

Answer 7

CNS neurons; ependymal cells (inner lining of ventricles, make CSF); oligodendroglia; astrocytes.

Question 8

What does neural crest give rise to?

Answer 8

PNS neurons, Schwann cells (peripheral myelination)

Question 9

What does mesoderm give rise to?

Answer 9

Microglia (Macrophages, originate from Mesoderm)

Question 10

Neural tube defects

Answer 10

Neuropores fail to fuse (4th week)→ persistent connection between amniotic cavity and spinal canal.

Low Folic Acid before and during pregnancy

Elevated alpha-fetoprotein (AFP)

Increased acetylcholinesterase (AChE)

Question 11

Spina Bifida (neural tube defect)

Answer 11

Failure of caudal neuropore to close→bony spinal canal doesn’t close.

1. Occulta: No herniation, dura intact, associated with faun tuft of hair or dimple at defect level
2. Meningocele: meninges bulge with CSF. Normal AFP
3. Meningomyelocele: meninges and cord herniate.

Question 12

Anencephaly (forebrain anomaly)

Answer 12

Malformation of anterior neural tube= no forebrain, open calvarium.

“frog-like” appearance

Clinically: incr AFP; polyhydramnios (no swallowing center).

Associated w/ maternal DM type 1

Maternal folate supplementation decr risk.

Question 13

Holoprosencephaly (forebrain anomaly)

Answer 13

Failure of Lt and Rt hemispheres to separate; usually during weeks 5-6. May be related to mutation in sonic hedgehog signaling.

Clinically: moderate form has cleft lip/palate, severe form results in cyclopia.

Question 14

Arnold-Chiari posterior fossa malformation (Chiari II)

Answer 14

Herniation of cerebellar tonsils and vermios through foramen magnum w/ aqueductal stenosis and hydrocephalus.

Often presents w/ myelomeningocele and paralysis.

Question 15

Dandy-Walker (posterior fossa malformation)

Answer 15

Agenesis of cerebellar vermis w/ cystic enlargement of 4th ventricle (fills the enlarged posterior fossa).

Associated w/ hydrocephalus and spina bifida.

Question 16

What do the 1st and 2nd branchial arches form?

Answer 16

Anterior 2/3 of tongue

(sensation via CN V₃, taste via CN VII)

Question 17

What do the 3rd and 4th branchial arches form?

Answer 17

Posterior 1/3 of tongue

(sensation and taste mainly via CN IX, extreme posterior CN X)

Question 18

What are the musculoskeletal and neural derivatives of each pharyngeal arch?

Answer 18

1st: CN V₃, malleus, incus, mylohoid, ant belly digastric

“muscles of mastication”

2nd: CN VII, stapes, stapedius,stylohoid, post belly digastric, “muscles of facial expression”
3rd: CN IX, stylopharyngeus
4th: CN X (superior laryngeal), soft palate, pharynx
6th: CN X (recurrent), larynx and exophagus

Question 19

Choanal Atresia?

Answer 19

Improper opening of choanae due to failure of apoptosis of oronasal membrane.

“My newborn is having difficulty breathing and can’t breastfeed”

“My daughter’s nose is always running; she cannot breathe through it.”

Question 20

Anterior lip and palate defects

Answer 20

Failure of fusion of maxillary prominences with the fused medial nasal prominences.

1 in 1000 births and 60-80% males increasing with increasing maternal age.

Question 21

Posterior palate defects

Answer 21

Failure of fusion of the palatine shelves with one another with the nasal septum and with the posterior margin of the primary palate.

Involves hard and soft palate.

1 in 2,500 births, 2x as common in girls. No link to maternal age.

Wide variation: all of hard and soft palate, only soft palate, only uvula (bifid); unilateral of bilateral.

Question 22

Fetal Alcohol Syndrome (FAS)

Answer 22

Characteristic facial features: flat face, small palpebral fissures, small jaws

Predominantly neurological features (only 4-6% show physical signs).

1st trimester: interferes w/ migration, organization

2nd: difinitive FAS traits
3rd: hippocampus, problems w/ math, reading

Question 23

Congenital coloboma

Answer 23

Defective closure of the choroid or optic fissure.

Positioned in the inferonasal quadrant, relective of the location of the optic fissure during fetal development.

Question 24

External Ear Malformation

Answer 24

Failure of 1st cleft to invaginate.

part of several syndromes: first arch syndromes, chromosomal abnormalities.

Present as:

• Auricular appendages/tags from excess hillock mesenchyme
• Auricular cysts (fistulas) from incomplete fusion of hillocks
• Microtia: abnl shape or size of ear, varies in severity.
• Anotia: agenesis, inner may be normal.

Question 25

Congenital Neurosensory Deafness

Answer 25

Abnormal development of cochlea, CN VIII, or brainstem ## Footnote Causes: - Rubella in 1st trimester→defects in organ of corti in 30% of cases - Neural crest defect→migratory melanocytes from NC don't properly form stria vascularis

Question 26

Congenital conduction deafness

Answer 26

Persistence of meatal plug (1st arch syndrome) ## Footnote - Fixation of footplate of stapes - Abnormalities of malleus and incus often

Question 27

Microopthalmia

Answer 27

Arrested development of optic vesicle; globe is small, lens doesn't form

Question 28

Anopthalmia

Answer 28

Arrested development of optic vesicle early in 4th week, usually accompanies severe craniocerebral defects.

Question 29

Congenital Glaucoma

Answer 29

Cloudy cornea from abnormally high intraocular pressure, usually from malformed drainage apparatus. Genetic abnormalities account for 85% of cases, also Rubella. Cupping on eye exam.

Question 30

Persistent hyaloid artery of pupillary membrane

Answer 30

Failure of either to dissolve in development. Hyaloid artery: normal regression ~11 weeks and completely gone by 8 months. Pupillary membrane: may interfere w/ visual acuity.

Question 31

CHARGE syndrome

Answer 31

**C**oloboma **H**eart defects **A**tresia of choanae **R**etarded growth/development **G**enital hypoplasia **E**ar abnormalities

Question 32

Congenital Ptosis

Answer 32

Does not affect vision, correctable via surgery by tightening LPS Autosomal dominant Result from birth trauma, myasthenia gravis, abnl CNIII development, or dysgenesis of LPS.

Question 33

Nasolacrimal groove atresia

Answer 33

Results in canalization failure, infection is common, and newborn may have constant tearing/mucuous drainage, and subsequent chapping of periocular skin.

Question 34

Microtia

Answer 34

Grade 1: Ear slightly smaller than nl; no surg needed Grade 2: Auricle half-size; surgery beneficial Grade 3: Small cartilage present; repair at age 5-6

Question 35

Lop ear

Answer 35

Most common external ear abnormality; absence of antihelical fold, cosmetic surgery offered.

Question 36

Prequricular pits and fistulas

Answer 36

Frequently infected pits in front of ear Tx: w/ antibiotics and incision and drainage

Question 37

Auricular appendages

Answer 37

Arrested development of fusion of the hillocks of His. Growth that contains cartilage and skin. Tx: elective excision

Question 38

Derivatives of 1st-4th pharyngeal pouches?

Answer 38

1st: Auditory tube, mastoid air cells 2nd: Palatine tonsils 3rd: Thymus and inferior parathyroid 4th: Thyroid and superior parathyroid

Question 39

First Arch Syndrome?

Answer 39

Treacher Collins Syndrome: -fishmouth appearance, midface deformity, thin lower face, small jaw Pierre Robin Syndrome: -cleft palate, posterior displaced tongue, micrognathia. -Tx: tracheostomy, mandible lengthening hardware

Question 40

DiGeorge syndrome?

Answer 40

No thymus or parathyroids (3rd and 4th pouch) Low immunity and hypocalcemia

Question 41

Ectopic thyroid, parathyroid or thymus

Answer 41

Accessory or ectopic parathyroid are highly variable in number and location. Inferior may fail to descend, remain near bifurcation of carotic artery. May be found in thorax w/ thymus. Accessory thymus tissue: portions of the tail may break off and found in the thyroid, in association w/ the inferior parathyroid or in isolated "nests"

Question 42

Lateral cervical cyst and fistula

Answer 42

Branchail cleft, 2nd arch most common ## Footnote Lump located along the anterior border of SCM muscle, below angle of the mandible. Due to incomplete overgrowth of the 2nd, 3rd, 4th clefts by the 2nd arch.

Question 43

Thyroglossal duct cyst of fistula

Answer 43

Remnant of thyroglossal duct Midline - usually near hyoid, but may be from the base of the tongue down to thyroid cartilage. May be associated w/ URI sxs.

Question 44

Ankyloglossia

Answer 44

Lingual phrenulum still attached, can't breast feed.

Question 45

Congenital megacolon or Hirschsprung's disease?

Answer 45

Neural crest cells fail to migrate into colon; parasympathetic gangli do not form → no peristalsis Usually sigmoid colon and rectum, fecal retention

Question 46

Waardenburg syndrome?

Answer 46

Diffuse disruption of neural crest cell migration. ## Footnote Abnormal face appearance, deafness, lack of pigmentation (melanocytes), digestive problems (enteric ganglia)

Question 47

Cranial Malformations

Answer 47

due to craniosynostosis; premature closure of sutures 1. Scaphocephaly: sagittal sutures = long narrow head 2. Oxycephaly: coronal and lambdoidal sutures; tower 3. Brachycephaly: bilat coronal suture; wide skull 4. Plagiocephaly: unilateral coronal or lambdoidal 5. Trigonocephaly: frontal (metopic); pointy forehead Deformational Plagiocephaly: positional malformations from laying on back, may require different sleeping postion or helmet.

Question 48

Apert Syndrome

Answer 48

Autosomal dominant; mutation in fibroblast growth factor receptor 2 gene. ## Footnote Sx: under developed face, symmetric syndactyly, hearing loss/freq infection, short stature, slow Cruzon synd: similar to Apert but only craniofacial.

Question 49

Microcephaly

Answer 49

small head, usually due to underdeveloped brain. Mentally deficient. May be genetic or due to radiation exposure, infectious agents, drugs/EtOH, rubella, or chicken pox

Question 50

Cranioschisis

Answer 50

Cranial vault fails to close due to failure of cranial neuropore to close usually in occipital region. (similar to spina bifida in the posterior head)

Question 51

Hydrocephalus

Answer 51

Build-up of CSF in brain →ventricle enlargement →pressure on cortex →brain damage 1 in 1000 live births

Question 52

Neurocranium vs viscerocranium

Answer 52

Neurocranium: develops around rostral end of the neural tube, gives rise to bones surrounding brain and special sense organs. Viscerocranium: develops around the gut tube, gives rise to lower face, jaws, palate, larynx, hyoid, epiglottis.

Question 53

Facial Primordia (week 4)

Answer 53

1. 5 facial prominences(neural crest→pharyngeal arch) a. frontanasal: mesenchyme ventral-brain vesicles b. maxillary(2): extension from 1st pharyngeal arch c. mandibular(2): mesenchyme 1st pharyngeal arch 2. Placodes (ectodermal thickenings→special sense) a. lens placode: lens b. otic placodes: inner ear c. nasal placodes: nasal cavity and part upper lip 3. Stomodeum(ectoderm depression→future mouth site

Question 54

Palate formation

Answer 54

forms between weeks 5-12 (critical 6-9) ## Footnote Primary palate from intermaxillary segment. Secondary palate from palatine processes of maxillary prominences growin medially; fuse anterior to posterior (uvula region fuse ~12 weeks) Primary/Secondary fusion = incisive foramen Hard palate (primary palate + rostral 2° palate = intramembranous bone) forms from maxilla and palatine bones.

Question 55

Congenital cataracts

Answer 55

cloudy or opaque lens. May be inherited, caused by rubella virus or congenital galactosemia.

Question 56

Coloboma

Answer 56

Failure of optic fussure to close, may leave gap anywhere along it's path. ## Footnote Anterior coloboma (of iris) presents as a key-shaped pupil, usually in inferior nasal quadrant. vision may be normal. retinal or optic nerve proximal defects produce large deficits in visual field.

Question 57

Detached Retina

Answer 57

RPE is adhered to choroid but neural and RPE layers not adhered to one another. Poor fusion in development. May be co-morbid with Marfan or Down synd.