Genetic Disease + Congenital Abnormality Flashcards
Features of Trisomy 21
Down's flat occiput single palmar creases incurved fifth finger wide ‘sandal’ gap between the big and second toe short neck hypotonia epicanthic folds small ears, small mouth, protruding tongue Brushfield spots: White spots on iris Excessive joint laxity
Areas to examine in newborn with suspected Down’s
Eyes: cataracts, glaucoma
GI tract:
Heart:
How does trisomy 21 occur
94% non dysjunction in meiosis = gamete with 2x Chr21
5% Robertsonian translocation
1% mosaicism
Health problems with Down’s syndrome
Hirschsprung’s + Duodenal atresia
Congenital cardiac abnormalities: VSD, AVSD
T1DM
GORD
Atlanto-axial instability
Increased susceptibility to infections
Incr risk leukaemia
Incr risk epilepsy + Parkinson’s (esp early onset), hypothyroidism
Hearing impairment following chronic infections
Visual impairment due to cataracts
Sev-mod learning ?, delayed motor development
Hypothyroidism
45XO
Turners syndrome
At birth: lymphoedema, coarctation, aortic stenosis
Short stature, delayed puberty, thyroid disorders
Horseshoe kidney
Coeliac disease
47 XXY
Klinefelter’s syndrome
Tall stature
Delayed puberty
Gynaecomastia
Prader Willi
Imprinting: loss of paternal Chr 15
Almond shaped eyes, narrow forehead, carp shaped mouth
Cryptorchidism
Genital hypoplasia
Strabismus
Hypotonia and poor feeding initially, later obesity due to hyperphagia
Low IQ
Di George’s
Microdeletion - FISH diagnosis 22q 11.2 Cleft palate Thymic hypoplasia Hypocalcaemia Aortic arch abnormalities
William’s
Microdeletion
Trisomy 13
Patau’s
Trisomy 18
Edward’s
Duchenne’s muscular dystrophy
X linked - dystrophin gene 30% de novo mutation Most common Delayed walking Gower's sign Pseudo hypertrophy of calves
Fragile X
X linked recessive
Multiple CGG trinucleotide repeats on X Chr
Female carriers: mild learning disability
Affected males: mod learning disability avg IQ50, macrocephaly, macro-orchid ism, large ears, long face, prominent mandible + forehead
Galactosaemia
Deficiency in galactose-1-phosphate uridyl transferase
Vomiting
Cataracts
Recurrent E.coli sepsis
PKU
AR = defective phenylalanine hydroxylase
Accumulation of phenylalanine -> phenylketones
Developmental delay + learning difficulties
Musty smelling urine
Seizures, microcephaly
Screened in Guthrie, newborn blood spot
Req phenylalanine free diet for life
Marfan’s syndrome
AD - fibrillin gene
Musculoskeletal
Ocular
Cardiac
Becker’s muscular dystrophy
X linked - dystrophin gene
Less severe than duchenne
Muscle weakness
Delayed motor milestones
Homocysteinuria
AR
Thromboembolic tendency
Myotonic dystrophy
AD
Hypotonia from birth
Myasthenia Gravis
Delayed walking
Fatigueability
CAH
Unable to metabolise testosterone to produce cortisol
Masculinised female genitali/ abnormal male genitalia
Salt losing crisis: low glucose + vomiting
Replace glucose and steroids
Noonan’s
Male + female affected Developmental delay Happy demeanour Aortic stenosis Poor feeding and weight loss as neonate Overeating and obesity later
VACTERL
Vertebral Anal imperforation Cardiac Tracheo-oesophageal fistula Limb abnormalities
CHARGE
Coloboma Heart defects Atresia choanae Retardation of growth + dev GU abnormalities Ear abnormalities
Tetralogy of Fallot
VSD Right ventricular hypertrophy + outflow tract obstruction Overriding aorta Presents ~ 6 months Cyanotic spells
Gastroschisis
Herniation of bowel through anterior abdominal wall Not covered with membrane Not associated with other abnormalities Fluid, electrolyte + heat losses Dehydration, hyponatraemia, hypothermia
Asymmetrical IUGR
Late pregnancy insult:
GDM, pre-eclampsia,
Symmetrical IUGR
Early pregnancy insult (from 1st trimester)
Chromosomal anomaly
Maternal smoking/alcohol use
Congenital infection
Wiskott-Aldrich
X linked - WASp gene actin affected Eczema Thrombocytopenia Recurrent infection (Petechiae, bruising)
NBSS: newborn blood spot screening
Aka Guthrie card
Congenital Hypothyroidism
PKU
CF
(SCD + thalassemia)
Features of CHT: congenital hypothyroidism
Hypotonia
Coarse facies
Features of fetal alcohol syndrome
Thin top lip
Short nose
Small eyes + hypertelorism (incr distance betw eyes)
Causes of cerebral palsy
Permanent non-progressive lesion in the developing brain
Prenatal:
Delivery:
Post natal:
General features of cerebral palsy
Abnormal tone in first yr of life: initially hypotonic -> spasticity
Delay in gross motor development/ abnormal movements
Primitive reflexes persist longer than usual: Moro + grasp
Assoc issues: learning difficulties, epilepsy, visual impairment, hearing loss, speech disorders, behavioural disorders, resp problems
Spastic cerebral palsy
70%
Hemiplegic
Diplegic
Quadriplegic
Less common types of cerebral palsy
Ataxic:
Dyskinetic:
Mixed:
Osteogenesis Imperfecta type 1
AD
Bony fragility = recurrent fractures + deformity
Wormian bones on skull X Ray: irreg isolated bones
Blue sclerae
Conductive hearing loss: 50%
Aortic valve regurg: diastolic murmur
What is Gastroschisis?
Defect in ant abdo wall adjacent to umbilicus
Abdo contents can herniated through the defect
No sac covering contents
Immed management = cover exposed viscera
Surgical repair
Rarely assoc with any other congenital malformation
What is exomphalos?
Herniation of the abdominal contents through the umbilicus
Herniated viscera are surrounded by sac: amnion = omphalocele
Surgical closure required
50% assoc with other congenital malformations
What is Meckel’s diverticulum?
Congenital diverticulum with gastric type mucosa
A true diverticula it incorporates all layers of the wall from which it arises
2 feet proximal to ileocaecal junction
2 inches in length, 2% of population
Painless rectal bleeding
Susceptible to peptic ulceration
Dx confirmed by technetium99m scan as only taken up by gastric type mucosa
Resection may be required
Developmental dysplasia of the hip
Ranges from partial subluxation to frank dislocation
6x more common in female infants
L hip > R hip
RF: +ve fhx, breech delivery, spinal/neuromusc abnormalities, oligohydramnios
How is DDH identified?
Neonatal screening using Barlow + Ortolani's tests At birth At 6 wks Good +ve predictive value Poor -ve predictive value
Late presentation of DDH
Asymmetrical skin folds
Limited abduction
Shortening of affected limb + limp
How is DDH managed?
Conservative: for several months
abduction in Craig’s splint / restraining device Pavlik harness
Monitor progress on USS or X-ray
Failure of conservative methods -> open reduction + femoral osteotomy
Complication: necrosis of femoral head
Talipes equinovarus
Aka clubfoot
Foot inverted + plantar flexed
1/500 births 50% bilat
Causes: secondary to intrauterine pressure e.g. Oligohydramnios, or neuromusc disorder e.g. Spina bifida
Management of talipes equinovarus
Passive stretching + strapping
Severe deformity may require corrective surgery
William’s syndrome
AD microdeletion 7q11
Short stature
Elf-like faces, transient hypercalcaemia, supra valvular aortic stenosis
Mild-moderate learning disability
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Microdeletion
