Cytogenetic imbalance (loss) Flashcards
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- del 5p (variable size)
- Contiguous gene deletion syndrome
Phenotype:
- High pitched cry
- Microcephaly
- Micrognathia
- Low set ears
- Epicanthal folds
- Severe psychomotor and ID (evident 1st year)
- Most frequently do novo with low recurrence risk (gonadal mosaicism a possibility)
- Recurrence risk higher for carriers of balanced translocations
Wolf-Hirschhorn syndrome
- del 4p
- WHSC1, LETM1, and MSX1 deletion found in those with classical features
-Congenital malformation syndrome
-Pre and postnatal growth deficiency
-Severe ID
-Seizures
-Characteristic craniofacial features (Greek warrior helmet features):
Prominent forehead
Hypertelorism (wideset eyes)
Broad beaked nose
-Closure defects (cleft lip or palate, coloboma of the eye, and cardiac septal defects)
- 90% de novo
- ring chr4 (breakage and fusion with loss of distal material)
- Parent with balanced translocation
Miller-Dieker syndrome cytogenetic abnormality
- Terminal deletion 17p
- PAFAH1B1 (LIS1) deletion responsible for lissencephaly
- usually de novo
Miller-Dieker syndrome phenotype
-Lissencephaly (smooth brain with lack of gyri due to incomplete neuronal migration)
-Severe ID and dev delay
-Seizures (prior to 6 months)
-Spasticity and hypotonia
-Facial features:
prominent forehead
midface hypoplasia
low set abnormally shaped ears
upturned nose
Smith-Magenis syndrome cytogenetic abnormality
Interstitial deletion of proximal 17p
4Mb common deletion region
Deletion of RAI1 thought responsible for most characteristic features
Smith-Magenis syndrome phenotype
Mild/moderate ID Delayed speech and language Sleep disturbance Behavioural problems Characteristic facial features: -Broad square face -Deep set eyes Full cheeks -Prominent lower jaw -Down turned mouth with upward curving lip
Mechanism of recurrent microdeletion/duplication syndromes
usually de novo due to NAHR between regions of homology interspersed through the genome
polymorphic regions of low copy repeats
2 LCRs in close proximity pre-disposes to NAHR and del/dup of intervening sequence
DiGeorge syndrome cytogenetic abnormality
del(22)(q11.2)
1.5-3Mb
Contiguous gene deletion syndrome
Reciprocal duplications exist
Gene TBX1 thought to be responsible for characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels)
Autosomal dominant inheritance usually de novo
May be inherited from phenotypically normal parent
DiGeorge syndrome phenotype
Variable phenotype affecting numerous parts of the body
Heart abnormalities Cleft palate Distinctive facial features Breathing problems Kidney abnormalities Hypocalcaemia (may result in seizures) Thrombocytopenia Feeding difficulties Delayed speech LD
Williams-Beuren Syndrome cytogenetic abnormality
Contiguous gene deletion syndrome
1.5-1.8Mb deletion on chr 7q11.23 encompassing ~28 genes
del(7)(q11.23)
Williams-Beuren Syndrome phenotype
Heart defects ( supravalvular aortic stenosis) Elfin-like features Mild/moderate ID Hypercalcaemia Difficulty with visual-spacial tasks Short stature Cocktail party manner
broad forehead
short nose
full cheeks and lips
dental problems
Microdeletion syndromes
Angelman/PWS 15q11q13 Williams 7q11.23 Velo-cardio-facial 22q11 Rubinstein-Taybi 16p13.3 Miller-Dieker 17p13.3 Smith-Magenis 17p11.2 Langer-Giedion 8q24.1 Wilms-aniridia 11p13 1p36 del
Velo-cardio-Facial syndrome
22q11 deletion
Heart defects
LD and psychosis
Facial features: Cleft palate Nasal voice Bulbous nose Almond shaped eyes Round ears
1p36 deletion
Slow growth and development Deep set eyes Horizontal eyebrows Cleft lip and palate Microcephaly Delayed fontanelle closure Severe LD Epilepsy Cerebral atrophy Congenital heart disease
