Genetic Conditions Flashcards
Which chromosomal abnormality is present in Down Syndrome?
Trisomy 21
Give some clinical features of Down Syndrome which might be present at birth
Flat facial profile - flat occiput, round face, flat nasal bridge Single palmar crease Hypotonia Congenital heart disease (affects 30%) e.g. VSD, patent ductus arteriosus Incurved 5th finger 'Sandal' gap between 1st and 2nd toes Duodenal atresia Speckled irises (Brushfield spots) Squint Upward slanting, almond eyes
What is the prevalence of Turner’s Syndrome
About 1 in 2500 live girls, although 95% results in early miscarriage
Give some clinical features of a person with Turner’s Syndrome
Short stature (may be only feature) Widely spaced, often inverted nipples Wide chest Congenital heart defects Spoon-shaped nails Webbed neck Wide carrying angle (cubitus valgus) Lymphoedema Renal abnormalities Pigmented moles Normal intellect
What is meant by dysmorphology?
This is the description and evaluation of physical features which are frequently associated with genetic disorders
What is the most commonly inherited trisomy?
Trisomy 21 - Down Syndrome
What is the most common cause of the mutation in Down Syndrome?
Meiotic non-dysjunction: Error at meiosis causes failure of chromosome 21 to separate, so one gamete has 2 x chromosome 21 and another has none. When the gamete with two of the same chromosome fuses with a normal gamete in fertilisation, this gives rise to a zygote with trisomy 21.
True / False: About 95% of Turner Syndrome cases result in miscarriage
True
What are the clinical features of William Syndrome?
- Congenital heart disease particularly supravalvular aortic stenosis
- Characteristic facies: Puffy cheeks, flat nasal bridge
- Transient neonatal hypercalcaemia in 15%
- Mild / Moderate learning difficulties
Which chromosome is affected in William Syndrome?
Chromosome 7
Which chromosome is affected in Di George Syndrome?
Chromosome 22 (band q11 is deleted)
What is the inheritance pattern of neurofibromatosis?
Autosomal dominant
What is the inheritance pattern of tuberous sclerosis?
Autosomal dominant, although up to 70% of cases are new mutations
From which parent are mitochondrial disorders inherited?
Mother
What is MELAS?
A mitochondrial disorder:
Mitochondrial encephalitis
Lactic acidosis
Stroke-like episodes
What is MERRF?
A mitochondrial disorder:
Myoclonic epilepsy with ragged red fibres
What is DIDMOAD
A mitochondrial disorder: Diabetes insipidus Diabetes mellitus Optic atrophy Deafness
What is the pattern of inheritance of tuberous sclerosis?
Autosomal dominant
What is the pattern of inheritance of neurofibromatosis?
Autosomal dominant
What is the pattern of inheritance of Fragile X syndrome?
X-linked
List some features of Fragile X syndrome
Moderate to severe learning difficulties Autism Long face Large ears Large testes (after puberty) Prominent mandible Joint laxity Mitral valve prolapse Scoliosis
Which blood marker is raised in Duchenne muscular dystrophy?
Creatine kinase (CK)
You are presented with a female infant with coarctation of the aorta. There is no family history but you notice a short, webbed neck and a ‘sheild-shaped’ chest. What diagnosis would you suspect?
Turner’s syndrome
Supravalvular aortic stenosis is found in a 3-year-old boy with learning difficulties might lead you to suspect which genetic condition?
Williams syndrome
What is the gene defect in Fragile X syndrome?
Expanded repeat of CGG sequence at the 5’ end of FMR-1 gene (Fragile X Mental Retardation-1) on xq27. The number of repeats increases down subsequent generations.
What is the inheritance pattern of achondroplasia?
Autosomal dominant
What is the inheritance pattern of phenylketonuria?
Autosomal recessive
What is the inheritance pattern of Wilson’s disease?
Autosomal recessive
What is the inheritance pattern of Duchenne and Becker muscular dystrophy?
X linked
What is the inheritance pattern of glucose-6-phosphate dehydrogenase deficiency?
X linked
What is the inheritance pattern of Huntington’s disease?
Autosomal dominant
What is the inheritance pattern of congenital adrenal hyperplasia?
Autosomal recessive
What is clinodactyly and when might you see it?
Incurving of a digit - seen in Down’s syndrome (incurving of the 5th finger)
What is Trisomy 18?
Edward’s syndrome
What is the chromosomal abnormality in Kleinfelter’s syndrome?
XXY
What is the principle feature of Kleinfelter’s syndrome?
Male hypogonadism
What is Trisomy 13?
Patau’s syndrome
How do you manage Turner’s syndrome?
Growth hormone therapy to increase height - Somatropin
What is the chromosomal abnormality in Turner’s syndrome?
Complete or partial absence of one of the X chromosomes (XO)
What is the genetic abnormality in Duchenne muscular dystrophy?
Mutation in dystrophin gene on chromosome 21
What are the clinical features of Duchenne muscular dystrophy?
Usually in early childhood Gross motor delay 'Clumsiness' Proximal myopathy and weakness Calf pseudohypertrophe Progressive muscle dysfunction leading to respiratory failure
What is Gower’s sign? When might you see it?
Seen in Duchenne muscular dystrophy - Ask child to sit down and then stand up…they will need to roll over and ‘climb up themselves’ in order to stand due to proximal muscle weakness
Which is more severe…Duchenne or Becker muscular dystrophy?
Duchenne muscular dystrophy - presents earlier and is more severe
How are the facial features of Williams syndrome sometimes described?
‘Elfin’
List some features of Di George syndrome
Remember ‘CATCH 22’:
Congenital heart disease - especially ToF
Abnormal facies
Thymic dygenesis - causes T cell deficiency
Cleft palate
Hypocalcaemia
Rocker bottom feet is a feature of which genetic condition?
Edward’s syndrome
Which genetic condition has karyotype XO?
Turner’s
Antenatal blood tests showing low serum alpha-fetoprotein (AFP), unconjugated oestriol and hCG, might indicate which genetic condition?
Edwards Syndrome (Trisomy 18)
XXY chromosomal abnormality is which condition?
Kleinfelters
