Assessing Growth & Pubertal Development & Paediatric Genetics Flashcards
How do you put the height of the child into perspective?
According to parental heights
Target height & mid parental height (MPH)
How do we assess bone age?
TW20
- Xray of hand
- Severe osteopenia confuses interpretation
- Pathological conditions can distort bones
What assessment tools are used for development?
- Height/length/weight
- Growth charts & plotting
- MPH & target centiles
- Growth velocity
- Bone age
- Pubertal assessment
What are some common causes of short stature?
- Familial short stature
- Constitutional delay of growth & puberty
- SGA/IUGR
What investigations can be done in short stature & pubertal delay?
- FBC & ferritin (coeliac, chron’s, JCA)
- U&E, LFT, Ca, CRP (disorders of Ca metabolism)
- Coeliac serology & IgA
- Look for hormonal disorders (cortisol, TFT, IGF-1, prolactin)
- Karotype/Microarray (Turner’s syndrome, chromosomal abnormalities)
How do you confirm growth hormone problems?
GH stimulation- 2 tests
- Arginine test
- Insulin tolerance test
What is used to assess puberty?
Tanner staging
Breast, genital, pubic hair, axillary hair & testicular volumes
What is the difference between stage 1 & stage 2 in the tanner staging?
Stage 1=Pre-pubertal
Stage 2=Beginning of puberty
Pubertal tempo is also important
What hormones are responsible for the production of secondary sexual characteristics (pubic & axillary hair)?
Adrenal hormones
What are the definitions of early & delayed puberty in boys compared to girls?
BOYS:
Early=<9years (rare)
Delayed=>14 (common, especially CDGP)
GIRL
Early=<8years
Delayed=>13years (rare)
CDGP is in boys mainly: what is needed to exclude?
Need to exclude organic disease
- Bone age delay
- FH
What is the tanner staging of breast budding and testicular enlargement?
-Breast budding (Tanner stage B2) in a girl
- Testicular enlargement (Tanner stage G2-T4 ml)
What is the karotype of Turner syndrome?
45X0
- Short stature
- Ovarian dysgenesis
What are some associated problems with Turner syndrome?
Associated disorders: cardiac, renal, thyroid, ENT problems
Psychosocial/educational difficulties
Physical stigmata (web neck, childlike proportions etc)
How are girls with Turner syndrome treated?
GH
Prader willi syndrome: what causes it and what are the signs of it?
Deletion of 15q11-q13 chromosomal region
- Infantile hypotonia/feeding problems
- Hyperphagia/obesity in childhood
- Short stature
- Developmental delay
- Hypogonadism
Give GH
Noonan syndrome is associated with what features?
- Typical facial features
- Short stature
- Congenital HD (pulmonary valve stenosis)
What is achondroplasia (short limbed dwarfism) associated with?
- Long bones don’t grow properly
- Supportive management
What are the causes of delayed puberty?
- Chronic disease & constitutional
- Primary gonadal disorders (Gonadal dysgenesis (Turners, Klinefelter’s,DSD), testicular irradiation)
- Impaired HPG axis (septo-optic dysplasia, craniopharyngioma, Kallman’s syndrome)
What is central precocious puberty?
- True pubertal development (breast development & testicular enlargement
- Growth spurt
- Advanced bone age
Need to exclude pituitary lesion—MRI
What is see in precocious pseudopuberty?
- Secondary sexual characteristics
- Gonadotrophin independent (low/prepubertal levels of LH & FSH0
- Most common early adrenarche
Need to exclude congenital adrenal hyperplasia
OBESE + SHORT = ?
ABNORMAL
What are the causes of obesity in children?
- Simple obesity
- Drugs
- Syndromes
- Endocrine disorders
- Hypothalamic damage
Investigations are rarely necessary
What are a few things to watch for in the case of an obese child that might need further investigation?
Endocrine causes—Growth failure
Syndromes—Learning difficulties
Hypothalamic causes—Loss of appetite control
Genetic causes—Starts before age 5
What are the 4T’s of diabetes symptoms?
Thirsty
Tired
Thinner
using the Toilet more
What is a red flag symptom for diabetes in children?
A return to bedwetting or day wetting in a previously dry child
In children under 5 what should also be thought about in relation to diabetes?
- Heavier than usual nappies
- Blurred vision
- Candidiasis (oral, vulval)
- Constipation
- Recurring skin infection
- Irritability, behaviour change
What are the symptoms of DKA?
- N & V
- Abdo pain
- Sweet smelling ketotic breath
- Drowsiness
- Rapid, deep ‘sighing’ resp
- Coma
How to test in diabetes suspected?
Finger prick capillary glucose test
Result > 11 mmol/l=Diabetes
<11=another cause
Should children be reviewed the same in diabetes?
YES, Same day review
- DKA can occur very quickly in children
- Don’t delay diagnosis
What is Trisomy 21 (Down syndrome) associated with?
- Learning disability
- CHD
- Hypothyroidism
- Immune issues
- Early onset Alzheimer disease
Non-invasive prenatal testing will mean more of these pregnancies are detected prenatally
How is down syndrome screened for?
Prenatal screening for Down syndrome is regarded as standard of care in Western obstetrics
Non-invasive prenatal testing using next-generation sequencing of free fetal DNA in maternal blood is no risk to fetus
Ethical issues of Is a world without Down syndrome acceptable?
What other trisomy’s are also common except Trisomy 21?
Trisomy 13
Trisomy 18
Big variation in survival-majority die in early life
What is a syndrome?
A pattern of clinical features occurring together
How do we diagnose a rare intellectual disability +/or a malformations syndrome?
History
Description
Recognition of patterns
Testing:
- Standard- biochemical, chromosome structure
(Microarray now standard)
- Targeted testing
- Moving to trio-based exome / genome
How do we describe a dysmorphic child?
Position and shape of facial features
Hands
Growth of child
General features
What do we look at on the head in terms of genetic abnormalities?
HEAD:
- Shape
- Size (macrocephaly, microcephaly)
- Ear position (low set, posteriorly rotated indicates lack of maturity)
What abnormalities of the eyes and hands can be seen in genetic conditions?
EYES
- Hypertelorism (Inner canthal distance ICD and inter-pupillary distance IPD increased)
- Telecanthus / epicanthic folds
(ICD and IPD increased)
HANDS
Finger length
Digital abnormalities
Palmar creases
Examples Marfan syndrome, Down syndrome
What is a sign in the hands of Marfan’s syndrome?
Arachnodactyly
MF/THL is usually >44%
What is Brachydactyly?
Short, fat fingers
Does malformation always occur alone?
Can occur alone or as part of a syndrome
eg. polysyndactylty alone (Hox D13 one cause)
or acrocephalopolysyndatyly (Greig / GLI3) (Tall forehead, polydactyly & syndactyly)
A sequence is when abnormality leads to another, can have multiple cause: what are some examples of this?
Pierre-Robin sequence=small chin to cleft palate
Fetal akinesia sequence
- reduced fetal movement
- reduced breathing
- contractures
- clefting
- lung hypoplasia
How is fetal akinesia picked up?
20 week scan
- Abnormal limb position
- Reduced fetal movements
- Mild polyhydamnios?
What is deformation & disruption?
Pattern of development normal to start with but becomes abnormal
Deformation-organ parts are there
Disruption-Part of organ/body part absent
E.g. Amniotic bands
What is deformation & disruption?
Pattern of development normal to start with but becomes abnormal
Deformation-organ parts are there
Disruption-Part of organ/body part absent
E.g. Amniotic bands
What is association specifically VATER association?
Two features or more features occur together more often than expected by chance
- mechanism unclear
VATER
vertebral anomalies/VSD
ano-rectal atresia
tracheo-oesophageal fistula
radial anomalies
What is a syndrome?
A distinct group of symptoms & signs which, associated together, form a characteristic clinical picture or entity
Cause may or may not be known
What are the signs and associations of Turner syndrome (45 X)
Lymphoedema (Puffy feet, nuchal translucency / cystic hygroma)
Increased carrying angle, low hairline, wide sp nipples, sandal gap
Short stature, occ. v mild learning diffy
Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension
Primary amenorrhoea & infertility
Hormonal therapy mitigates some features
What genetic investigations are done for learning disability?
Microarray
Fragile X
Targetted tests driven by phenotype
Trio based Exome vs. trio-base genome analysis
Funding remains an issue
Trio-based exome in Scotland and genome in England!
What complications are associated with 22q1 deletion (Di george)?
Cleft palate
Abnormal facies
Thymic hypoplasia / immune deficiency
Calcium abnormalities
Heart problems
Caused by 22 deletion
“CATCH 22”
How is Glut1 deficiency: SLC2A1 deletion or mutation (epilepsy condition example) treated?
With ketogenic diet
Copy number variants and sequence variation is normal so how can thousands of genes be tested and still find the cause of intellectual disability?
Whole-Exome Sequencing of Germline DNA
Why is phenotyping important?
The key to assessment of clinical relevance is the phenotype
That’s why accurate description of clinical features is important
A diagnosis helps the family see the future- can help with future pregnancy planning, clinical care and treatment
