Genetics Flashcards
Incidence of Down Syndrome in live births
1 in 650
Signs of Down Syndrome x7
Facies, hypotonic, flat occiput, short neck, single palmar creases, incurved 5th finger, wide ‘sandal’ gap between big and second toe
Heart disease in Down Syndrome
Congenital heart disease in 30%
Atrioventricular septal defect is a major cause of early mortality
Later medical problems with Down Syndrome x6
Delayed motor milestones Learning difficulties Short stature Increased susceptibility to infection Hearing impairment Visual impairment
Why hearing impairment in Downs Syndrome?
Due to secretory otitis media
Disease risks with down syndrome x5
Increased risk of leukaemia and solid tumours Increased risk of hypothyroidism Coeliac disease Epilepsy Alzheimer's Disease
What is Edwards Syndrome? Incidence
Trisomy 18, 1 in 8000 live births Micrognathia Low-set ears Rocker bottom feet Overlapping fingers
What is Patau Syndrome? Incidence
Trisomy 13, 1 in 14,000 live births Microcephalic Small eyes Cleft lip/palate Polydactyly Scalp lesions
Features of Patau and Edwards
Very severe mental and physical disabilities
Majority of affected babies die in infancy
What is 45, XO, incidence
Turner syndrome, 1 in 2500 of live born females
Consequence of Turner syndrome
> 95% result in early miscarriage
Features of Turner Syndrome x11
Short stature (may be only feature) Spoon-shaped nails Neck webbing Wide carrying angle (cubitus valgus) Delayed puberty Infertility due to ovarian dysgenesis Hypothyroid Renal abnormalities Lymphoedema of hands and feet in neonate which may persist Congenital heart defects Recurrent otitis media
Treatment of Turner Syndrome x2
Growth hormone therapy - can counter short stature
Oestrogen replacement for development of secondary sexual characteristics at time of puberty
What is 47, XXY, incidence
Klinefelter Syndrome
1-2/1000 live born males
Features of Klinefelter x5
Infertility (most common presentation) Hypogonadism Gynaecomastia Tall stature May have some educational and psychological problems but intelligence usually normal
What increases incidence of autosomal recessive disorders
Consanguinity
Arab cultures this is more common
Disorders which have trinucleotide repeat expansion mutations x5
Fragile X Myotonic dystrophy Huntingtons disease Spinocerebellar ataxia Friedreichs ataxia
X-linked dominant inheritance disease
Hypophosphatemic (vitamin D-resistant) rickets
What is Fragile X Syndrome? Incidence
Significant learning difficulties in males, x-linked recessive but also trinucleotide expansion
Incidence 1 in 4000
Females and fragile x
Female carriers can have mild learning difficulties
Number of repeats needed for symptoms in Fragile X
CGG trinucleotide needs more than 200 copies of repeat - this is caused by gene with full mutation
Other clinical features of Fragile X in males
Macrocephaly
Macro-orchidism post puberty
Strabismus
Long face, large everted ears, prominent mandible and broad forehead
Mitral valve prolapse, joint laxity, scoliosis, autism and hyperactivity
Syndromes involving imprinting
Prader-Willi syndrome - absence of functional paternal copy of region will develop PWS
Angelman - failure to inherit functional maternal copy leads to this rather than PWS
Same region
Features of PWS x4
Hypotonia Developmental delay Hyperphagia Obesity Hypogonadism
Features of Angelman syndrome x4
Severe cognitive impairment
Characteristic facial impairment
Ataxia
Epilepsy
Definition of malformation
Primary structural abnormality occurring during development of tissue or organ
Definition of deformation
Abnormal intrauterine mechanical force that distorts a normally formed structure - eg. due to oligohydramnios
Definition of disruption
Destruction of fetal part which initially formed normally eg. amniotic membrane rupture may lead to amniotic bands which may cause limb reduction defects
Definition of dysplasia
Abnormal cellular organisation or function of specific tissue types
eg. skeletal dysplasias
What are single-system defects?
Single congenital malformations eg. spina bifida - which are often multifactorial in nature with fairly low recurrence risks
What are sequence birth defects?
A pattern of multiple abnormalities occurring after one initiating defect
eg. Potter syndrome following from oligohydramnios
What are association birth defects?
A group of malformations that occur together more often than expected by chance but in different combinations from case to case
What are syndrome birth defects?
A particular set of multiple anomalies occurs repeatedly in a consistent pattern - common underlying causal mechanism
Craniofacial appearance in Down’s syndrome
Round face Flat nasal bridge Upslanted palpebral fissure Epicanthic folds Brushfield spots in iris Small mouth and protruding tongue Small ears Flat occiput and third fontanelle
GIT abnormalities in down syndrome
Duodenal atresia
Hirschsprungs disease
Intellectual ability in Turners
Normal usually
Features of Noonan syndrome
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis (Congenital heart defects)
Features of Pierre-Robin syndrome
Micrognathia
Posterior displacement of the tongue (can cause upper airway obstruction)
Cleft palate
Features of William’s syndrome
Short stature Learning difficulties Friendly, extrovert (highly verbal despite low IQ) Transient neonatal hypercalcaemia Supravalvular aortic stenosis
