genetic Flashcards
what are the clinical features of Down’s syndrome?
- face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set ears, round/flat face
- flat occiput
- single palmar crease, pronounced ‘sandal gap’ between big and first toe
- hypotonia
- congenital heart defects (40-50%, see below)
- duodenal atresia
- Hirschsprung’s disease
what are the cardiac complications in Down’s syndrome?
- multiple cardiac problems may be present
- endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
- ventricular septal defect (c. 30%)
- secundum atrial septal defect (c. 10%)
- tetralogy of Fallot (c. 5%)
- isolated patent ductus arteriosus (c. 5%)
what are the later complications of Down’s syndrome?
- subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, and have an increased incidence of problems with pregnancy and labour
- learning difficulties
- short stature
- repeated respiratory infections (+hearing impairment from glue ear)
- acute lymphoblastic leukaemia
- hypothyroidism
- Alzheimer’s disease
- atlantoaxial instability
A 10-year-old boy is found to have haemophilia A following investigation for a haemoarthrosis. Which one of his relatives is most likely to have the condition?
Mother’s brother
X-linked recessive conditions are only seen in males
male to male transmission is not seen
what is the genetic condition associated with Hirschsprung’s disease?
Down’s syndrome
section of bowel with abnormal nervous supply –> reduces normal peristaltic motion –> delayed passage of meconium + chronic constipation in childhood
chromosome 5q deletion and typically presents with a high-pitched cry in infancy?
Cri du chat sydnrome
small jaw, low-set ears, rocker-bottom feet and overlapping fingers?
Edward’s syndrome, trisomy 18
mild-moderate learning difficulty, a long and narrow face, large ears, flexible fingers and large testicles?
Fragile-X syndrome
caused by a trinucleotide repeat expansion and is inherited in an X-linked dominant fashion
webbed neck, pectus excavatum, short stature and pulmonary stenosis?
Noonan syndrome
autosomal dominant inheritance
microcephaly, small eyes, cleft lip/palate, polydactyly and scalp lesions?
Patau’s syndrome (trisomy 13)
cleft palate, posterior displacement of the tongue and a small jaw
the underlying cause of this syndrome remains poorly defined, although oligohydramnios, connective tissue disorder and genetic defects have been postulated.
Pierre-Robin syndrome
spontaneous deletion on chromosome 5 in the majority of cases. Typical features include hypogonadism, hypotonia and obesity.
Prader-Willi syndrome
- presence of only one X chromosome, resulting in a 45,X0 genotype.
- Patients are genetically and phenotypically female.
- presents with multiple overlapping features with Noonan syndrome although is more associated with bicuspid aortic valve and coarctation of the aorta.
Turner’s syndrome
most commonly caused by a random genetic deletion on chromosome 7. Typical features include mild to moderate learning difficulty and a friendly, extroverted personality.
William’s syndrome
what is the mode of inherintance for Duchenne muscular dystrophy?
X-linked recessive
what are the features of Duchenne muscular dystrophy?
- progressive proximal muscle weakness from 5 years
- calf pseudohypertrophy
- Gower’s sign: child uses arms to stand up from squatted position
what is Duchenne muscular dystrophy associated with?
- dilated cardiomyopathy
- intellectual impairment (30%)
what are dystrophinopathies due to?
mutation in the gene encoding dystrophin, dystrophin gene on Xp21
dystrophin is a part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton
what is the milder form of muscular dystrophy and what are its features?
Becker muscular dystrophy
- develops after age of 10
- intellectual impairment much less common
