Chromosomal Syndromes - PAEDS Flashcards
Define these terms:
Malformation
Deformation
Disruption
Dysplasia
Single system defect
Sequence
Association
Syndrome
Malformation → primary structural defect occurring during the development of a tissue/organ
Deformation → abnormal intrauterine mechanical force that distorts a normally formed structure (e.g. oligohydramnios)
Disruption → destruction of a foetal part that may have initially formed normally
Dysplasia → abnormal cellular organisation or function
Single system defect → single congenital malformations
Sequence → pattern of multiple abnormalities occurring after one initiating defect (i.e. posterior urethral valves)
Association → group of malformations that occur together but in different combinations case to case
Syndrome → multiple abnormalities occurring repeatedly in a consistent pattern, common underlying causal mechanism
How do these maternal behaviours affect the foetus/neonate?
foetal alcohol syndrome cigarette smoking rubella varicella syphilis infection
Foetal Alcohol Syndrome: Microcephaly, absent philtrum, cardiac abnormalities, reduced IQ, IUGR, small upper lip
Cigarette smoking: IUGR, miscarriage, stillbirth
Rubella (<16w most risk): TRIAD: Cataracts, deafness, cardiac abnormalities
Varicella (1% if infected 3-28w): Skin scarring, eye defects (small eyes), neurological defects (low IQ, microcephaly)
Syphilis: infection Rhinitis, saddle-nose, deafness (sensorineural), hepatosplenomegaly, jaundice
What is Patau’s Syndrome?
Investigations?
Trisomy 13; 1 in 14,000 births
· 80% die in first month of life, 90% by 1 year of age
USS analysis in 2nd trimester
o Chromosomal analysis from amniocentesis/cffDNA (NIPT)
What is Edward’s Syndrome?
Trisomy 18; 1 in 14,000 births
· Many will die in infancy, but prolonged survival is possible
· Associated with Exomphalos / Omphalocele
USS analysis in 2nd trimester
o Chromosomal analysis from amniocentesis/cffDNA (NIPT)
What is Noonan’s Syndrome?
Autosomal dominant with a normal karyotype (affects both males and females)
· Penetrance varies greatly (from lethal prenatally to minimal morbidity)
What is Prader-Willi Syndrome?
Management of PWS?
Imprinting - expression of gene is influenced by sex of paretn who transmitted it
Lack of paternal - PWS
Lack of Maternal - Angelman
can be de novo deletion or uniparental disomy
Growth hormone if clinical evidence of growth failure
Management of feeding and obesity (i.e. lock cupboards)
What is Turner’s Syndrome?
1 in 2500
affects females, 45 X
Neonate: pyloric stenosis, cardiac abnormalities, renal anomalies, cystic hygroma, ovarian dysgenesis -> infertility
management -
growth hormone therapy
oestrogen replacement - not for fertility but secondary characteristics
What is Kleinfelter’s SYndrome
1-2 per 1,000 males live-born
· Normal appearance and normal IQ
Taller than average
absent/delayed or incomplete puberty
What is fragile X syndrome?
X-Linked recessive inheritance
1 in 4,000 births
usually males
trinucleotide repeat-expansion mutation like Huntington’s
Genetic counselling to families
What is Down’s Syndrome?
Trisomy 21 - most common cause of intellectual disability
94% meiotic non-disjunction
5% translocation
1% mosaicism
Signs and symptoms of down’s syndrome?
round face flat nasal bridge epicanthic folds brushfield spots small mouth small ears flat occiput 3rd fontanelle short neck single palmar crease
Down’s syndrome complications in the neonate?
congenital heart defects
duodenal atresia
hirschsprung’s disease
omphalocele +/- umbilical hernia
Down’s Syndrome complications later on?
Delayed motor milestones secretory otitis media learning difficulties visual impairments short stature obstructive sleep apnoea
Management of Down’s Syndrome?
immediate: echocardiogram genetic counselling physiotherapy SALT - speech therapy
later: annual hearing test SEN haemoglobin for IDA OSA monitoring growth monitoring
