Flashcards in 18.07.43 Chromosome 20 Deck (15):
What are some of the phenotypic features of chromosome 20?
1) Mild mental retardation
2) Short stature
3) Facial dysmorphism
- high forehead
- broad nasal bridge
- thin upper lip
- small chin
- malformed ears and hands
What are some of the features of 20p12.3 microdeletion syndrome?
Implicated in Wolf-Parkinson-White, a pre-excitation disorder associated with specific EKG findings, tachycardia
Studies have shown association between 20p12.3 and WPW and cognitive delay
Clinical phenotype may be the result of BMP2 gene
What is the phenotype and typical presentation of Alagille syndrome?
Typically presents with neonatal jaundice
dysmorphic features - deep-set eyes, broad forehead
What is the incidence and the genetic spectrum of Alagille syndrome?
1 in 70,000 AD variants in JAG1 (20p12.2) aka Alagille-Watson syndrome orateriohepatic dysplasia
90% of cases due to AD sequence variants in JAG1
5-7% are deletions in JAG1
1% are variants in NOTCH2 (1p13, Alagille syndrome 2)
>400 reported mutations
60% de novo
Germline mosaicism may occur in up to 8%
What are some of the differential diagnosis for Alagille syndrome?
Conditions that also involve paucity of the bile ducts
Primary pulmonary artery stenosis is also seen in Williams syndrome
Where is the GNAS imprinted locus? What clinical features are associated with deletions of this region?
Severe pre and post-natal growth retardation
Intractable feeding difficulties
Abnormal adipose tissue
Mild psychomotor retardation
What are the features of 20q13.33 microdeletion syndrome
1) Severe limb malformations
2) Skeletal abnormalities
3) Growth retardation
4) Development and speech delay
5) Mental retardation
6) Behavioural problems (autistic, hyperactive)
What are some of the characteristic features of patients with r(20) syndrome?
Childhood onset seizures - frequent daytime complex partial seizures, noctural tonic seizures
Other co-morbidities include:
Ring 20 is considered to be two significantly different syndromes in genotype and phenotype. Describe each.
1) Formed post-zygotically (therefore mosaic) from telomere-telomere fusion. FISH and array have shown no deterctable deletions. Age of onset of seizures related to the degree of mosaicism. May have seizure only phenotype.
2) Deletion of subtelomeric regions of p and/or q arms. Non-mosaic. More likely to have additional features, e.g. dev delay.
Three familial cases have been reported. 46,XN,r(20). Mosaic mother with mosaic children
Which genes are candidates for the observed phenotype in r(20) syndromes? Why has no strong genotype-phenotype correlation been established?
CHRNA4 and KCNQ with epilepsy
SOX12, MYT1, DNAJC5, EEF12A2, NTSR1 involvedi n brain development
Patients with subtelomeric deletions on chromsome 20 but no ring formation do not always present with seizures.
Supernumery ring chromsome 20 is a very rare cytogeneitc finding (~15 cases). No common phenotype has emerged, however there are a few frequently reported features, what are they?
1) Growth and psychomotor retardation
2) Low set ears
3) Hands and feet anomalies
Growth retardation is a common feature of ring syndromes.
Mosaic trisomy 20 is one of the most commonly observed aneuploidies in prenatal diagnosis and may exist in 3 forms. Describe each.
Placental mosaicism with an apparently normal phenotype in a child when born
Foetal mosaicism with phenotypic consequence.
What features have been reported with mosaic trisomy 20?
Phenotype correlates with the level of mosaicism. Trisomic cells rarely appear in the blood.
significant learning disabilities, despite normal intelligence.
What are the features of maternal UPD(20)?
Intrauterine growth restriction
Prominent feeding difficulties with failure to thrive
Majority of cases are due to trisomy resuce after meiosis II nondisjunction. Suggestive of a novel imprinting disorder of growth failure.