Congenital Development of Disease Symposium Flashcards
1
Q
What is Gastrulation?
A
- when the bilaminar disk of the embryo develops to form 3 distinct layers - usually around week 3
- ectoderm (from the epiblast)
- mesoderm (invading epiblast cells from the primary streak)
- endoderm (hypoblast replaced by epiblast cells)
2
Q
What happens during fertilization Day-1 ?
A
- Sperm and Ovum meet in Uterine Tube (usually in the ampulla) 12-24 hours after ovulation.
- Penetration of Corona radiate and Zona pellucida
- Fusion and 2nd meiotic division
- Acrosome reaction makes ovum impermeable to other sperm
- End- Zygote- has diploid (46 chromosomes)
3
Q
What happens in days 2-3 after fertilization?
A
- Cleavage occurs- this is the rapid process of mitotic divisions
- The first mitotic division occurs around 30 hours post-fertilization.
- By day 3 the fertilized ovum has become a 16 cell embryo
- Each cell is known as a blastomere.
- forming a solid sphere is known as a morula.
4
Q
What happens day 4-5 post-fertilization?
A
- Morula develops a cavity and becomes known as a blastocyst.
- The outer layer of the blastocyst thins out and becomes the trophoblast this helps form the placenta
- The rest of the cells move (are pushed up) to form the inner cell mass. This creates an embryonic pole.
- The blastocyst has now reached the uterine lumen and is ready for implantation.
5
Q
What happens day 6-7 post-fertilization?
A
- the Bilaminar Disc forms- As the embryo starts to implant it forms two layers.
- Inner cell mass differentiates into two layers: epiblast and hypoblast.
- These two layers are in contact.
- Hypoblast forms extraembryonic membranes
- Epiblast forms embryo
- the Amniotic cavity develops within the epiblast mass
6
Q
What happens day 6-8 post-fertilization?
A
- The Primary Yolk Sac is formed
- it is derived from the hypoblast is the exocoelomic membrane. (aka Extraembryonic hypoblast/membrane)
- The Yolk Sac contains nutrients that supply the embryo before the placenta functions.
7
Q
How has the embryo developed by week 4?
A
- the flat disc has to fold into 2 directions
- Longitudinal (cephalocaudal) (day 21) begins so that head and tail are brought closer.
- Lateral (transverse) (day 18) brings the amniotic cavity down, creating the future gut tube inside the peritoneal cavity.
8
Q
Describe the structure of the Mesoderm
A
- formed of three parts
- Paraxial mesoderm
- Lateral plate mesoderm
- Intermediate mesoderm
- these structures are either side of the notochord
- this is made from the mesoderm
- remains as the nucleus palposus, the inside part of the vertebrae throughout embryonic development
9
Q
Explain what happens to the Paraxial mesoderm and what its role is in the development
A
- Paraxial mesoderm undergoes further differentiation into paired blocks of tissue- somites
- 42-44 pairs eventually formed (prep for the vertebral arch)
- Somites undergo differentiation to form dermomyotomes and sclerotomes
- Dermomyotomes: form connective tissue and skeletal muscle
- Sclerotomes: form bone and cartilage- vertebral arch
- __the cells from the sclerotome come around the neural tube and form the boney arch (spinous process)
- if they don’t come around and join completely –> spinabifida
10
Q
Label the structures of this Somite
A
11
Q
What is the role of the Intermediate mesoderm?
A
- it gives rise to the urogenital system
- kidneys - from the pronephros then mesonephros then the metanephros
- gonads
- urogenital ducts and associated glands
- formed from the degenerating excretory tubules of the mesonephros and pronephros
12
Q
What is the role of the Lateral plate mesoderm?
A
- creates the parietal and visceral layers
- Continuous with the amniotic sac and yolk sac.
- Amniotic sac mesoderm–> Parietal or somatic layer
- Yolk sac mesoderm–> Splanchnic layer
- Mesodermal cells will become the membranes of the body (pericardium, pleura, peritoneum)
- all cavities are lined with lateral plate mesoderm to form tha parietal layer and the visceral layer
- this then begins to fold to form a horseshoe shape creating an Intraembryoinc cavity which is u shaped
- the bend in the U becomes the pericardial cavity
- limb of U becomes 2 cavities pericardioperitoneal (pleural) and peritoneal cavities.
13
Q
Give an overview of the development of the pharyngeal clefts and pouches
A
- Clefts separate the arches externally.
- First cleft is the only one that contributes towards the adult structures: external acoustic meatus
- The endoderm of the foregut grows and forms pouches which become: auditory tube, tonsils, thymus and parathyroid gland.
- 1-4 well developed, 5th absent
14
Q
Give an overview of the development of the face week 4-5
A
- Development begins in week 4 and forms from 5 swellings.
- Frontonasal
- Maxillary X2
- Mandibular X2
By week 5 two events occur:
- Maxillary prominences enlarge in the medial direction
- Nasal placodes appear and form medial and lateral processes
15
Q
Give an overview of the development of the face week 6-8
A
- Maxillary prominences enlarge in the medial direction
- the maxillary prominences fuse with the lateral and medial nasal processes to form the upper lip
- Nasal placodes appear and form medial and lateral processes
- medial nasal processes merge towards each other and form intermaxillary segments
16
Q
How is the Palate formed?
- consequences fo improper formation?
A
- Develops from the fusion of the primary and secondary palate
- Grows obliquely down and then elevates
- Fuses in the midline at palatine raphe
- At the same time frontonasal process and medial nasal processes form nasal septum
- if this doesn’t occur properly this results in a cleft palate/ lips
17
Q
Give an overview of Ear formation
A
- Eyes and ears arise from ectodermal placodes
- Placodes are thickened areas of ectoderm which have interacted with the neural tube.
- External and middle ear derived from first 2 pharyngeal arches and cleft and pouch
- Inner ear develops at day 22 into otic placode.
- Otic vesicle enlarges and forms 2 parts: Dorsal vestibular portion- semicircular canals and Ventral cochlear portion- cochlea
18
Q
Give an overview of Tongue formation
- anterior
- posterior (pharyngeal)
A
Anterior Tongue
- 3 tongue buds form from 1st arch
- The distal buds (lateral lingual swellings) expand and fuse and overgrow the median bud to form the anterior tongue.
Pharyngeal tongue (posterior)
- Two swellings from 2nd, 3rd & 4th arches.
- V-shaped line represents the line of fusion, with a midline depression (foramen caecum- the origin of the thyroid gland)
- Hence different innervation of the tongue
19
Q
What is the innervation for different parts of the tongue?
A
- CN V3 - oral sensation (1st arch) blue
- CN VII - oral taste (2nd arch) red
- CN IX - pharyngeal taste/sensation (3rd arch) green
20
Q
What does LKA stand for?
- what is it, when is it used
A
- Leukotriene receptor antagonist
- this is a low dose ICS
- used in under 5’s
21
Q
Why is a specific diagnosis of disease important?
A
- can lead to a specific treatment
- allows you to counsel the parents more accurately
- genetic counselling for future pregnancies
- estimate recurrence risk
- prenatal diagnosis & intervention where possible
22
Q
How do you classify Single defects?
- examples
- recurrence risk
A
- Defect involves just a single structure
- Child otherwise “Normal”
- Examples - CDH, CTEV, Cleft lip/palate, CHPS, cardiac septal defects, neural tube defects
- Multi-factorial (?unknown)
- Recurrence risk: 2 to 6%
23
Q
How can single defects present?
A
-
Malformation
- localised defect during differentiation
- CHPS, cardiac septal defects
-
Deformation
- structural alteration after ‘normal’ differentiation
- CDH, CTEV
-
Disruption
- Structural destruction of a previously ‘normally’ formed part
- due to entanglement, disruption of blood supply
24
Q
What is Pyloric Stenosis?
- prevalence
- management/treatment
A
- constriction of the pyloric sphincter
- occurs in 3 per 1000 live births
- usually in Males 4:1, first born
- presents with Non-bilious projectile vomiting at the 2nd week
- feeling Pyloric ‘tumor’ after a test feed. You can also see parelstlatic waves when they swallow
- this is in 60-80% of cases
- Hypochloremic (hypokalemic) metabolic alkalosis
- due to excess fluid loss when vomiting
- Treatment –> Pyloromyotomy
- small incision in the pylorus muscle - not too deep.
- allows baby to feed soon after the surgery
25
What is a Dysplastic Hip?
- presentation/ diagnososis
- management/treatment
* a Dislocated or dislocatable hip
* occurs more frequently in female 9:1, 1 in 1000 / 100 and Breech births
* can present with asymmetric skin folds
* **Barlow test** – try to dislocate
* **Ortolani test** – try to relocate the dislocated hip
* **_Clunk_** vs Click when the hip is relocated
* Early diagnosis –\> Conservative treatment (**Pavlik Harness**)
* Late diagnosis –\> Surgical correction, more specialist the later the diagnosis
26
What is Intestinal Atresias?
- presentation/diagnosis
- managment/treatment
* Obstructruction of the intestinal tract
* Oesophageal atresia (with/out TO fistula)
* Duodenal atresia
* Jejunal / Ileal atresia
* (incomplete – stenosis)
* Polyhydramnios
* Intestinal obstruction
* Emergency that needs surgery
27
What is a sequence single defect?
- give examples of the two main sequences
* Single defect, but it's multiple anomalies
* due to a cascade of secondary & tertiary errors in differentiation
* Examples
* Breech deformation sequence (not a deformation in itself but causes a sequence of events that cause deformation)
* Barthrocephaly, torticollis, facial asymmetry, dislocated hip, valgus deformities of the foot
* Amniotic band disruption sequence
* craniofacial and limb defects
28
What are Multiple defects and what are there cause?
* Several structural defects (at least 2 systems)
* Chromosomal abnormalities
* Single Gene mutations
* Teratogens
29
Give an overview of chromosomal abnormalities
- types of abnormalities
- types of syndromes caused
- causes of specific syndromes
* Abnormalities of Chromosomal number
* Trisomy – 21, 18, 13
* Monosomy – Mostly lethal; (Turner Syndrome)
* Abnormalities of chromosomal structure
* Deletions, micro-deletions, duplications, invertions – 4p-, 5p- etc
* Sex chromosome abnormalities
* 45XO, 47XXY, 47XYY
* **Mosaicisms** - more than two cell lines from a single zygote- associated with structural defects
* germline mosaicism is transmittable to offspring
* Fragile sites / Breakage syndromes
* **Imprinting / Uniparental disomy:**
* **Prada-willi syndrome:** paternal deletion of 15q11
* **Angelman syndrome:** maternal deletion of 15q11
30
What is Downs syndrome?
- common presenting features
* caused by Trisomy 21 (translocation)
* 1 in 660
* Typical facies
* Clinodactyly, Simian crease
* Congenital Heart Defects
* Duodenal atresia
* Hypotonia
* Delayed Development
* common facial features are
* Epicanthic folds, upslanting & narrow palpebral fissures, hypertelorism,
* flat nasal bridge, small chin, protruding tongue, low set ears,
* relatively small mouth and large forehead and sometimes microcephaly
* Good Social skills
31
Give an overview of Single Gene mutations
- what types are there
- what diseases are they associated with?
* Mutations or ‘pathologic’ variants
* For example
* Autosomal Dominant - Marfans, neurofibromatosis
* Autosomal Recessive - Phenylketonuria (PKU)
* X-linked Recessive - Haemophilia
* X-linked Dominant – Hypo Phosphataemic Rickets
* Maternal Inheritance – Mitochondrial diseases
* having an extended family history can be helpful with diagnosis
32
What is Neurofibromatosis Type 1?
-
* tumour formed on a nerve cell sheath, frequently symptomless but occasionally malignant.
* 1 in 4000; Autosomal Dominant defect - 17q11.2
* Variable penetration
* Neural crest cells – differentiation/migration
* Café-au-lait spots, neurofibromas, freckling, lisch nodules, bone lesions, optic glioma, must have a family history of NF1
* Disfiguring & varied features
* associated with Non-cancerous CNS tumours
* Health surveillance
33
Give an overview of Tertagoens that can cause defects
- what defects do they cause
* Infections
* **Congenital Rubella** causes:
* cataracts, blindness, deafness, IUGR, microcephaly, CVS anomalies and developmental delay
* Chemicals
* **Foetal alcohol syndrome**
* IUGR, facial features - short palpebral fissures, epicanthal folds, small jaw, thin upper lip, long philtrum
* cardiac defects, joint & limb anomalies and delayed development
* **Maternal Phenylketonuria (PKU)**
* miscarriage, microcephaly, dev. delay, cardiac defects
* Drugs
* **Thalidomide**
* **Valproate** ( used to treat epilepsy and bipolar disorder)
* neural development disorders
34
What is PKU?
* phenylketonuria
* a genetic disorder that causes increase levels of the amino acid phenylalanine in the body
35
What are the two main Non-random grouping defects (Associations) to be aware of when diagnosing defects?
* **VATER association**
* **V**ertebral
* **A**no-rectal
* **T**racheo-Oesophagal fistula
* **R**enal/Radial anomalies
* **CHARGE association**
* **C**oloboma
* **H**eart defects
* **A**tresia Choanae
* **R**etarded growth
* **G**enital anomalies
* **E**ar anomalies
36
What is the diagnostic process when presented with Cafe au lait spots?
What are differentials for Cafe au lait spots?
_Diagnostic process_
* Look for other features
* Special examinations
* Imaging
* Blood tests
* Genetic testing
* Consult databases
* Consult specialists
* Review in few years
_Differentials_
* “Normal”
* Neurofibromatosis
* McCune Albright Syndrome
* Ataxia telangiectasia
* Tuberous sclerosis
* Gauchers disease
* Russell Silver syndrome
