Genetics Flashcards
Patau’s syndrome
Trisomy 13
Cardiac defects - VSD, PDA, dextrocardia
Microcephaly (and brain defects) Microphthalmia (small eyes) Other eye defects Cleft lip/palate Polydactly Omphalocele/Gastroschisis
80% die in first month, 90% in 1yr
Ix: USS analysis in 2nd trimester
Chromosomal analysis from amniocentesis/cffDNA (NIPT)
Edward’s syndrome
Trisomy 18
LBW Small mouth/chin Low-set ears Rocker-bottom feet Overlapping fingers Intellectual disability Cardiac, renal and GI abnormalities Omphalocele/Gastroschisis/EXomphalos
Many die in infancy
Ix: USS analysis in 2nd trimester
Chromosomal analysis from amniocentesis/cffDNA (NIPT)
Noonan’s syndrome
AD - Mutated RAS/Mitogen activated protein kinase
Webbed neck Trident hairline Pectus excavatum Short stature Pulmonary stenosis
Prader-Willi and Angelman’s syndrome
del (15q)
PWS - lack paternal
Angelman’s - lack maternal
PWS: Fat, floppy, flaccid Hypotonia Hyperphagia Almond shaped eyes Hypogonadism Obesity in later childhood Epicanthal folds Flat nasal bridge + upturned nose Learning disability
Angelman's: Myoclonic seizures/Epilepsy Cognitive impairment Ataxia Abnormal facial appearance
Management:
Growth hormone if clinical evidence of growth failure
Management of feeding and obesity
Turner’s syndrom
Female - 45 X
Neonatal signs: pyloric stenosis, cardiac problems (coarctation), renal anomalies, cystic hygroma (skin on back of neck)
Lymphoedema of hands/feet in neonate Short stature, spoon shaped nails Wide carrying angle Thick or webbed neck Infertility Bicuspid aortic valve -> aortic coarctation (ejection systolic murmur over AV) Delayed puberty Hypothyroidism Omphalocele/Gastroschisis
Management: GH therapy (plot height on syndrome specific growth charts Oestrogen replacement (at time of puberty for development of secondary sexual characteristics)
Kleinfelter’s syndrome
Male - 47 XXY
Infertility Hypogonadism (small testicles) Gynaecomastia Tall stature Normal appearance Normal IQ
Fragile X syndrome
CGG trinucleotide repeat expansion mutation (fragile), FMR1 gene
IQ 20-80 Macrocephaly, macroorchidism Characteristic facies: large, low-set ears, long, thin face Autism, joint laxity, scoliosis Complication: mitral valve prolapse
Management: genetic counselling in fragile X families; mutation can expand between subsequent generations
Chromosomal pathogenesis of Down’s syndrome
Trisomy 21
94% - meiotic non-disjunction (linked to maternal age); error at meiosis, pair of chromosomes 21 fail to seperate
5% - Translocation - extra chromosome 21 has joined another chromosome (usually 14); Robertsonian translocation, parental Chr analysis is recommended, risk of recurrence 10-15% if mother is translocation carrier
1% - Mosaicism - milder phenotype; some cells normal, some trisomy; chromosomally normal zygote, non-disjunction at mitosis
Signs and symptoms of Down’s syndrome
Characteristic facies - round face, flat nasal bridge, epicanthic folds, brushfield spots in iris, small mouth, small ears, flat occiput, 3rd fontanelle Hypotonia and short neck Single palmar crease Sandal gap on feet Short stature Upslanting papebral fissues Flat occuput Congenital heart defects in 40% Omphalocele/Gastroschisis
Medical problems: at birth and later
+ Increased change of diseases
+ Associated congenital conditions
Birth: Congenital heart defects (40%, AVSD) Duodenal atresia Hirschprung's disease Omphalocele +/- umbilical hernia
Later: Delayed motor milestones Learning difficulty (low IQ) Short stature Secretory otitis media (75%) Visual impairment (25-50%) Obstructive sleep apnoea (50-75%)
Increases disease chance: Leukaemia - not ALL, but myeloid; transient myeloprolif Hypothyroid and coeliac Epilepsy Early-onset Alzheimer's
Joint laxity - screen for atlantoaxial instability if doing sports
Associated congenital conditions: Kostmann's syndrome Bloom syndrome Fanconi syndrome Diamond-Blackfan NF1 Li Fraumeni syndrome
Management in trisomy 21: immediate, later, supportive
Immediate:
- Echocardiogram (AVSD) and evaluation by paeds (duodenal atresia)
- Genetic counselling (rev. chrom results, risk of recurrence)
- Early intervention program if developmental delay is present: Physio, OT (fine motor/self care), SLT (speech, language delay)
Later:
- Annual hearing test, thyroid levels, ophthalmic evaluation (upto 5 yrs, then every 2)
- Appropriate education placement with individualised education plan
- Hb level for Fe anaemia
- Monitor for Sx sleep apnoea
- Monitor growth using Down’s growth charts
Supportive:
- Local DS clinic, access to parent support groups
- DS association -> local group, new parent pack, info for families and carers
- National DS society -> events and support
Foetal alcohol syndrome
Microcephaly, absent philtrum, cardiac abnormalities, reduced IQ, IUGR, Small upper lip
Effects of cigarette smoking on foetus
IUGR, miscarriage, stillbirth
Rubella infection effects
Most risk <16wks
TRIAD: cataracts, deafness, cardiac abnormalities
Varicella infection effects
1% if infected in 3-28wks
Skin scarring
Eye defects (small eyes)
Neuro defects (low IQ, microcephaly)
