Development Flashcards
What is one of the most common and stable epigenetic marks?
5mC (methylation)
How is gene expression different if a gene is methylated in the promoter region vs gene body?
Promoter - silenced
Gene body - expressed
When do the 2 waves of methylation occur during development?
One when egg/sperm are being formed
One after fertilisation
What effect do maternally imprinted genes usually have on growth?
Stimulate
What effect do paternally imprinted genes usually have on growth?
Regulate
Give an example of a maternally imprinted disorder
Prader-Willi
Constant hunger
Give an example of a paternally imprinted disorder
Angelman syndrome
Happy, mental retardation
What changes in DNA methylation occur in cancer?
Genome wide hypomethylation
CpG specific changes
What is DOHAD?
Developmental origins of human disease hypothesis (exposure during development causes susceptibility later in life)
How many babies have congenital anomalies?
1 in 33
What are the most common congenital anomalies?
Heart defects
Neural tube defects
Downs syndrome
What is the most common environmental cause (teratogen) of congenital anomalies?
Maternal medications
e.g. thalidomide, fetal vaproate syndrome
What causes diabetic embryopathy?
Poorly controlled diabetes in mother
Name 3 congenital infections
Zika virus
Rubella
CMV
Name 2 deletion syndromes
Di George syndrome
Williams syndrome
Name 2 autosomal dominant disorders
Noonan syndrome
Myotonic dystrophy
What molecule in serum correlates with severity of a neural tube defect?
AFP
When are CVS/amniocentesis done?
CVS after 11 weeks
Amniocentesis after 16 weeks
What investigations are done on a newborn with a suspected disorder of sexual development?
Genetics
Internal and external genitalia exam
Biochemistry investigations
How has management of DSD changed?
Less on intervention/surgery
More on hormone treatment
What are the three categories of DSD?
- 46 XX DSD
- 46 XY DSD
- Sex chromosome DSD
What are 46 XX DSD disorders?
Disorders of ovarian development or of androgen excess
What is 46 XX testicular DSD?
Phenotypically a male but genetically a female
Present after puberty
Treat with testosterone
What is 46 XX gonadal dysgenesis?
Phenotypically a failure but failure of ovarian development
What is fetal androgen excess?
Caused by congenital adrenal hyperplasia
Genetically female but male genitalia due to excess androgen
What is a potential life threatening complication of fetal androgen excess?
Salt wasting
- child cannot make enough aldosterone and cortisol so cannot maintain fluid homeostasis
What are 46 XY DSD disorders?
Disorders of testicular development and disorders of androgen synthesis/action
What is complete androgen insensitivity syndrome? (AIS)
Body cannot respond to testosterone
Genetically a man but phenotypically a woman
Why are contractions of the uterus during delivery of the placenta helpful?
Helps to stop PPH
What is the cervix like during pregnancy?
Closed to stop ascending infection
How is the cervix prepared for labour?
Inflammatory process mediated by hormonal changes (COX2 unregulated)
Which drug is used to induce labour?
PGE2
What happens to the resting membrane potential as gestation progresses?
Becomes more positive (myometrium more excitable)
What happens to connexin proteins towards the end of pregnancy?
Upregulated
More gap junctions
Increased intercellular communication causes more powerful contractions
What is the Ferguson reflex?
Reflex comprising the self-sustaining cycle of uterine contractions
How is pre term technically defined?
Before 37 weeks
Why might twins be delivered early?
Stress trigger
Lack of space
Early activation of physiological processes
How is labour initiated in humans?
NO progesterone drop
‘functional’ progesterone withdrawal
Increase in oestrogen concentrations
What does breast milk contain?
Lipids Casein Whey Nitrogen Lactose Immune factors
What are the 2 stages of lactation?
- Production and storage of milk in alveoli
2. Ejection of milk from alveoli to nipple
At what point in pregnancy are breast alveoli ready to produce milk?
16 weeks
How is lactation inhibited until the baby is born?
Progesterone and oestrogen suppress prolactin (these withdraw at onset of lactation)
What is the effect of suckling on prolactin release?
Stimulates prolactin release
How does suckling activate the neuroendocrine reflex?
Stimulates the production of vasoactive intestinal peptide (VIP) and reduces dopamine release –> more prolactin
What role does oxytocin have in breastfeeding?
Suckling stimulates oxytocin release
Oxytocin causes myoepithelial cells around the alveoli to contract forcing the milk out
What are the 5 classes of child development skills?
Motor Perceptual Language Cognitive Social
What are critical periods in development?
Defined periods where appropriate stimulation is required to ensure development
What is the hierarchy for brain development?
- Cerebellar/brainstem
- Posterior
- Anterior
When do brain development growth spurts occur?
24-25 weeks gestation
Early infancy
7-10 years
Early adolescence
What are the TORCH infections during pregnancy?
Toxoplasmosis Others Rubella Cytomegalovirus Herpes
How many adverse childhood experiences predict poorer health outcomes?
4 or more
What are the 4 domains of child development?
- Gross motor
- Fine motor and vision
- Hearing and language
- Social and emotional
What are the 4 stages of child development?
Infancy (0-2) Early childhood (2-6) Middle childhood (6-12) Adolescence (12-18)
What are the 5 stages of language development?
- Preverbal communication
- Phonological development
- Semantic development
- Syntax/grammar development
- Pragmatics development
When does the ‘naming explosion’ occur?
18 months
What age do babies have a preference for faces?
4 months
What are the three types of learning in children?
Conditioning
Habituation/dishabituation
Schematic learning
What are Piaget’s 4 stages of child cognitive development?
- Sensorimotor
- Preoperational
- Concrete operations
- Formal operations
At what age does separation anxiety and fear of strangers develop?
8 months
What age is social referencing learnt? (e.g. facial expressions)
10 months
When is the critical period for attachment?
6 months to 2 years (11-18 months is peak)
