Genetics/The Dysmorphic Child Flashcards
What is the Aetiology of Trisomy 21?
95% Non-disjunction
4% unbalanced translocation
1% Mosaic (mildest)
What is an unbalanced translocation and what other chromosome is involved in unbalanced translocation in Down’s Syndrome?
Unbalanced translocation is when translocation results in extra or missing genetic material.
In Down’s this is usually with chromosome 14
What is Brachycephaly?
Flat Occiput
What are brushfield spots
White spots arranged in a ring around the pupil
What is Cinodactyly? Where is it seen?
Shortened digit (usually 5th)
T21 and Russel-silver syndrome
You are asked to examine a patient with down syndrome. what do you expect to see when examining the hand (2)?
Single palmer crease
Cinodactyly
You are asked to examine a patient with down syndrome. what do you expect to see when examining the foot (2)
Sandle foot (Widely separated 1st and 2nd metatarsal)
Increased skin creases
You are asked to examine a patient with down syndrome. what do you expect to see when examining the head (2)
Microcephaly
Brachycephaly
You are asked to examine a patient with down syndrome. what do you expect to see when examining the eye (5)?
Brushfield spots, cataracts, squints, Upslanted palpebral fissure, Epicanthic folds
You are asked to examine a patient with down syndrome. what do you expect to see when examining the ear (1)?
What is the significance of this finding?
Low set ears (also seen in turner’s)
Short Eustachian tube => increased risk of otitis media. Many have chronic otitis media.
How would you know if ears are low or high set ears or just normal?
Draw an imaginary line from the corner of the eye to the ear where normally, 1/3 of the pinnaabove line
You are asked to examine a patient with down syndrome. what do you expect to see when examining the nose (1)
Flattened nasal bridge (gives rise to pseudohypertelorism)
You are asked to examine a patient with down syndrome. what do you expect to see when examining the mouth (1)
What is a complication that can arise from this finding?
Small mouth microstomia with protruding tongue
Sleep apnea
How do measure the mouth
draw vertical lines from the pupils down. That is a normal mouth. Bigger = macrostomia, smaller, microstomia
You are asked to examine a patient with down syndrome. what do you expect to see when examining the chin (1)
micrognathism
How do you measure the size of the chin?
Must be on the same plane as the forehead. If it is too small, its micrognathism, big it is prognathism.
What congenital heart disease can be found in many patients with Down’s? Explain it. How would you confirm this?
What effect would this have on the lungs?
AVSD: Atrioventricular septal defect
This is when there is a gap in the septum between the left and right side of the heart which allows blood to flow from the left to right side of the heart.
May cause pulmonary hypertension
ECHO
List complications associated with down syndrome with tests on how to confirm if present (list 5)
Delayed developmental milestones
High level of autoimmunity => Hypothyroidism (Hashimoto) => hypothyroidism (TFTs/TSH)
AND Coeliac Disease => Coeliac screen
Obstructive sleep apnea
Atlantoaxial instability
Duodenal Atresia
Hirschprung Disease
Congenital Heart Disease (AVSD) => ECHO
Acquired hip dislocation (X-ray)
Type 1 DM
What is Duodenal Atresia
abnormally closed or absent orifice in the duodenum
What is Hirchprung Disease?
Congenital disease with missing nerves to the large intestine causing atresia.
What investigations would you consider for a patient with down’s syndrome? (5)
FISH/RTPCR (real time PCR)
Specific growth charts for Down’s
Screen for hypothyroidism and Celiac Disease
Eye Examination at 4-6 weeks and 18-24 months
ECHO
Free glucose
Xray
How would you confirm a Dx of down syndrome
1) Antenatally
2) Postnatally
1) NIPT - Non-invasive prenatal testing (blood test) or Amniocentesis
2) RTPCR or FISH
Define
Plagiocephaly
Scaphocephaly
Frontal Bossing
Plagiocephaly: Flat in one area (not occiput => Brachycephaly
Scaphocephaly => Premature fusion
Frontal Bossing: Prominent
What is the medical term for eyebrows that meet in the middle?
Synophrys
What is the medical term for eyes that are wide apart?
Hypertelorism
While examining a patient you notice blue sclera what is this a sign of? What is the inheritance of this disease
Osteogenesis imperfecta (AD)
In terms of dysmorphic child, what syndrome has a prominent nose as a characteristic feature?
Rubinsteini Taybi Syndrome
When examining an ear, you notice a skin tag on the tragus. What is this associated with?
Goldenhar Syndrome
What is the Philtrum? What syndrome is it missing in?
What you thought was the nasolabial fold. It is in the midline above your upper lip.
Missing in Foetal alcohol syndrome
What is the medical term for small mouth? Where is it seen?
Microstomia in Down’s Syndrome.
You inspect a child with a cleft lip/palate what doe you suspect?
Trisomy 13, di George
What is the medical term for small chin. Big? Where is it seen?
Micro/PROgnathism
Down Syndrome
While inspecting a patient you notice that her neck extends wider than usual. What is this finding and where is this characteristically found?
Webbing of the neck found in Turner’s Syndrome and Noonan’s
While inspecting a patient you notice an absent thumb. What syndrome is this associated with?
Fanconi Syndrome
While inspecting a patient, you ask them to fan out their fingers and notice that two fingers on the right hand are not separating as well on the left. What is this clinical finding and what is it associated with?
Syndactyly, Trisomy 18
What inheritence is tuberosclerosis
Autosomal dominant
What inheritence is neurofibromatosis Type 1:
Autosomal dominant
What inheritence is cystic fibrosis
Autosomal recessive
What is the inheritence of hemophilia, colour blindness, and muscular dystrophy
Recessive X-linked
What is the inheritence of beta thallasemia and sickle cell anemia
Autosomal recessive
What is the inheritence of hypophosphatemic rickets
X-linked dominant
What are the cardinal features of Turner Syndrome
Short Stature, infertility, webbed neck, coarctation of the aorta, widely spaced nipples, aortic stenosis,
How is Fragile X syndrome Diagnosed?
Trinucleotide repeat expansion in gene FMR1 via molecular analysis.
What is the normal inheritance of these trinucleotide repeat disorders
Fragile X Syndrome
Friedriech ataxia
Most others
Most of these triplet repeat disorders are autosomal dominant except Friedrich ataxia which is autosomal recessive and fragile X syndrome which is Xlinked recessive
What are some clinical features associated with Fragile X-Syndrome (at least 5)
Note: These are most evident in an adult
Moderate-severe learning difficulty
Macrocephaly
Macroorchidism (large testes)
Characteristic Facies: Long face, !!large everted ears!!(also in Digeorge’s if 22:11), Prominent mandible and forehead.
Define “Imprinting”
It is when the expression of some genes are different based on the sex of the individual that has given you that gene.
e.g. Failure to receive the functioning gene from the father will give you Prader Willi (therefore 2 maternal genes) and failure from the mother will give you Angelman (therefore 2 paternal genes).
What are some clinical features associated with Prader Willi Syndrome (5)?
Hypotonia
Hypogonadism
characteristic facial features (almond eyes, triangular mouth)
Neonatal feeding difficulties but hyperphagia in adulthood
Faltering growth in infancy (short stature)
Developmental delay and learning difficulties
A baby is delivered and you notice that they are hypotonic. What 2 syndromes are you suspecting (genetics)
Down’s Syndrome
Prader Willi Syndrome
What is the most common mode of inheritance.
Polygenic
so if you dont know, say this especially if there is a quantitative component.
What are some clinical features of Noonan’s (give 3)?
Webbing of neck (also in turner)
Pectus Excavatum
short stature
congenital heart disease (ASD, pulmonary stenosis)
What is Iris Coloboma
Key-ring pupil, looks like it is oozing out.
