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)
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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)
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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.
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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.
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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
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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.
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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.
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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
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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
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10
Q

Label the structures of this Somite

A
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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
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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.
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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
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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
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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
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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
Q

What is a Dysplastic Hip?

  • presentation/ diagnososis
  • management/treatment
A
  • 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
Q

What is Intestinal Atresias?

  • presentation/diagnosis
  • managment/treatment
A
  • 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
Q

What is a sequence single defect?

  • give examples of the two main sequences
A
  • 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
Q

What are Multiple defects and what are there cause?

A
  • Several structural defects (at least 2 systems)
  • Chromosomal abnormalities
  • Single Gene mutations
  • Teratogens
29
Q

Give an overview of chromosomal abnormalities

  • types of abnormalities
  • types of syndromes caused
  • causes of specific syndromes
A
  • 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
Q

What is Downs syndrome?

  • common presenting features
A
  • 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
Q

Give an overview of Single Gene mutations

  • what types are there
  • what diseases are they associated with?
A
  • 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
Q

What is Neurofibromatosis Type 1?

-

A
  • 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
Q

Give an overview of Tertagoens that can cause defects

  • what defects do they cause
A
  • 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
Q

What is PKU?

A
  • phenylketonuria
  • a genetic disorder that causes increase levels of the amino acid phenylalanine in the body
35
Q

What are the two main Non-random grouping defects (Associations) to be aware of when diagnosing defects?

A
  • VATER association
    • ​Vertebral
    • Ano-rectal
    • Tracheo-Oesophagal fistula
    • Renal/Radial anomalies
  • CHARGE association
    • ​Coloboma
    • Heart defects
    • Atresia Choanae
    • Retarded growth
    • Genital anomalies
    • Ear anomalies
36
Q

What is the diagnostic process when presented with Cafe au lait spots?

What are differentials for Cafe au lait spots?

A

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