Autosomal deletions and duplications Flashcards
Prader WIlli
Chromosome 15 (q11-13) on paternal chromosome is affected (deleted or not expressed)
PWS incidence
M:F= 4:3
-1/10000-1/25000
PWS chromosome
15q11-12 paternal
characteristics of PWS in babies
- hypotonia
- lethargy
- hypogonadism
- breech
- failure to thrive
- sleepiness
- triangular mouth
HYperphargia in PWS
-80%!
Characteristics of PWS in adults
- obesity
- hypotonia
- infertility
- hypogondism
- sparse pubic hair
- LD/borderline intellectual functioning
- extreme flexibility
PWS physical appearance
- prominent nasal bridge and forehead
- small hnds and feet
- almond shaped eyes
- flattened face
- thin upper lip
- downturned mouth
- lack of sexual development
- striae
- delayed motor development
IQ in PWS
- IQ below 70 in over 90%
- autistic feautres reported in 15%
Angelman syndrome
- deletion of 15q12 of maternal origin
- 80% due to deletion of maternally derived chromosome 15
Angelman
`15q12 deletion maternal
Angelman prevalence
-rare, 1/20,000-1/30,000
Features of Angelman
- happy
- paroxysmal laughter
- hand flapping
- clapping
- ataxia
- severe/profound LD
Facial features in Angelman
- fair hair
- blue eyes
- microcehaly
- flattened occiput
- long face
- prominent jaw
- wide mouth
- widely spaced teeth
- thin upper lip
- pointed chin
Epilepsy and Angelman
- 90%
- EEG has highly characteristic changes as early as 3
Williams syndrome
- rare
- characterised by elfin appearance
- deletion of 26 genes from the long arm of chromosome 7
Williams occurrence
-occurs in around 1/7500 and 20,000
Presentation of Williams
- irritable
- feeding problems
- failure to thrive
- developmental delay
- growth retardation
- 60% have high calcium
- mild to moderate LD
Characteristic features of William’s syndrome
- short stature
- growth retardation
- elfin face
- hoarse voice
- renal and CV abnormalities
- thyroid abnormalities
- hypercalcaemia
- anxious, fearful. hypersensitive
- good verbal skills
- can be very friendly
Cri-du-CHat
- partial deletion at 5p15.2
- 85% deletions arise spontaneously
- majority are paternal origin
Cri-du-chat genetics
-5p15.2 deletion
Incidence of cri du chat
1/15,000 to 1/50000
-more common in females
Characteristics of cri du chat
- high pitched cry
- pronounced microcephaly
- round face with hypertelorism
- epicanthal folds
- slanting palpebral fissures
- broad flat nose
- low set ears
- micrognathia
- dental malocclusion
- severe to profound LD
Behavioural problems in Cri du CHat
- seen in large amounts but may improve with age
- self-injury, stereotypies, tantrums
- severe-profound LD
Smith-Magenis
complete or partial deletion of 17p11.2
Smith-Magenis incidence
1;25,000
LD and Smith-Magenis
- 75% have mild/moderate LD
- severity of impairment correlates with the size of the 17p11 deletion
Characteristic features of Smith Magenis
- flattened mid face
- abnormal upper lip
- short hands and feet
- simian crease
- protruding tongue
- high arched palate
- small toes
- hoarse deep voice
DI George syndrome
- 22q11.2 deletion
- velocardiofacial syndrome
Di George syndrome
- caused by microdeletion of chromosome 22 (22q11.2)
- 90% cases denovo
- 10% have ab affected parent
Prevalence of Di George
1/4000
LD in Di George
-over 50% have mild to moderate LD
Heart features in Di George
- tetralogy of Fallot
- VSD
- interrupted aortic arch
- pulmonary atresia
Facial features in Di George
- microcephaly
- cleft palate
- small mouth
- long face
- prominent tubular nose
- nasal speech
- narrow palpebral fissure
- small optic discs
Other features in Di George
- hypocalcaemia (60%)
- seizures
- short stature
- hearing problems
- renal problems
- inguinal/umbilcal hernia
- hypospadias
- long thin hands
Behavioural problems in Di George
- schizophrenia-like psychosis
- blunted affect
- most individuals have problems with social interaction
Rubinstein-Taybi syndrome
- microdeletions in 16p12.3
- very rare
- 1/125,000-300,000
Characteristics of Rubinstein-Taybi
- short stature
- moderate-severe LD
- distinctive facial features
- broad thumbs and first toes
- feeding difficulties in infancy
- congenital heart disease
- EEG abnormalities
- seizures
Behavioural features in Rubinstein-Taybi
- friendly disposition
- self-stimulatory activities
- intolerant of loud noises
