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Toronto Notes 2019
Syndromes and Diseases
Medical Genetics MG5
Physical Exam
Ears: structure, size, placement, rotation
Nose: nasal bridge, nostrils Philtrum: length, shape Mouth: lips, palate, tongue, teeth
Spine: scoliosis, kyphosis Skin: hair tufts, sacral
dimples, sinus Limbs: proportions, amputations
Face: gestalt
Skull: contour and symmetry
Hair: texture, pattern
Eyes: distance apart, brows, lashes, folds, creases, coloboma, fundus Chin: size, position
Neck: webbed, redundant nuchal skin Thorax: shape, size, nipple spacing
Genitalia: ambiguous Hands and Feet: creases,
structure, nails
■ karyotype if recognized aneuploidy syndrome
■ chromosomal microarray analysis (comparative genomic hybridization [array CGH]) if
developmental delay OR two or more congenital anomalies
■ FISH if aneuploidy syndrome (e.g. trisomy 13, 18 or 21) suspected
• biochemistry:variousbiochemicalprofiles,specificenzymeassays • singlegenetesting,multi-genepaneltesting
Management
• prenatalcounsellingandassessingriskofrecurrence
• referralforspecializedpediatricorgeneticcareforsymptomaticmanagement
• specifictreatmentsareavailableforcertainmetabolicdisordersandgeneticsyndromes
■ metabolic disorders: enzyme replacement therapy, substrate reduction therapy, etc. (e.g. low-protein diet in PKU patients)
■ genetic syndromes: e.g. mTOR inhibitors in tuberous sclerosis
Growth parameters (head circumference, height, weight)
Figure 2. Physical exam of the dysmorphic child
Investigations
• screeningforTORCHinfections • serialphotographsifchildisolder • x-raysforbonyabnormalities
• cytogeneticstudies
Check the umbilical cord for 2 arteries and 1 vein. Thepresenceofasingleumbilicalarterymaybe associatedwithothercongenitalanomalies
Syndromes and Diseases
Table 3. Common Chromosomal Aneuploidy Syndromes
Disease Incidence
Cranium/Brain Eyes
Ears
Facial Features Skeletal/MSK
Trisomy 21
Down syndrome
1:600-800 births
Most common abnormality of autosomal chromosomes Rises with advanced maternal age from 1:1,500 at age 20 to 1:20 by age 45
Mild microcephaly, flat occiput, 3rd fontanelle, brachycephaly
Upslanting palpebral fissures, epicanthal folds, speckled iris (Brushfield spots), refractive errors (myopia), acquired cataracts, nystagmus, strabismus
Low-set, small, overfolded upper helix, frequent AOM, hearing loss
Protruding tongue, large cheeks, low flat nasal bridge, small nose
Short stature
Excess nuchal skin
Joint hyperflexibility (80%) including dysplastic hips, vertebral anomalies, atlantoaxial instability
Trisomy 18
Edwards’ syndrome
1:6,000 live births F:M = 3:1
Microcephaly, prominent occiput
Microphthalmia, hypotelorism, iris coloboma, retinal anomalies
Low-set, malformed
Cleft lip/palate
Small mouth, micrognathia
Intrauterine growth restriction (IUGR)
Clenched fist with overlapping digits, hypoplastic nails, clinodactyly
Trisomy 13
Patau syndrome 1:10,000 live births
Microcephaly, sloping forehead, scalp defect, holoprosencephaly
Microphthalmia, corneal abnormalities
Low-set, malformed 60-80% cleft lip and palate
Small head size Polydactyly