Partial Chromosomal Deletions And Duplications ✅ Flashcards
What does the phenotypic effect of a deletion or duplication depend on?
The genes it encompasses
In general, is a deletion or a duplication more likely to have a phenotypic effect?
Deletion
Why can partial chromosomal deletions and duplications be hard to diagnose?
With conventional karyotype, many of the common pathogenic deletions and duplications are too small to be visible on conventional karyotyping
What was historically required to diagnose many chromosomal deletions and duplications?
The clinician to recognise the disorder and request the correct FISH test
What has made the diagnosis of partial chromosomal deletions and duplications much easier?
Array CGH
Why has array CGH made the diagnosis of partial chromosome deletions and duplications much easier?
- Much higher resolution than karyotyping
- Tests across the whole genome for microdeletions and duplications in a single test
What is the result of array CGH being better at detecting partial chromosomal deletions and duplications?
It has replaced karyotyping as the first line test for suspected chromosomal abnormalities in paediatrics
Give 2 microdeletion syndromes
- 22q11 deletion syndrome
- Williams syndrome
What is 22q11 deletion syndrome also known as?
- DiGeorge syndrome
- Velocardiofacial syndrome
What causes DiGeorge syndrome?
Deletion of 22q11 region of one copy of chromosome 22
What is the inheritence pattern of DiGeorge syndrome?
Autosomal dominant
Who else may be tested when a child is diagnosed with DiGeorge syndrome?
The parents
Why may it be helpful to test the parents when a child is diagnosed with DiGeorge syndrome?
The parents may have a milder phenotype and not be aware of it
Are more cases of DiGeorge syndrome inherited or de novo?
The majority are de novo
What are the characteristic facial features of patients with DiGeorge syndrome?
- Long face
- Narrow palpebral fissures
- Over-folded ear helices
What is the limitation of the identification of DiGeorge syndrome based on facial features?
The facial phenotype is often subtle
What medical complications might patients with DiGeorge syndrome experience?
- Cardiac defects
- Palatal abnormalities
- Immune deficiency
- Hypocalcaemia
- Renal tract abnormalities
- Mild to moderate learning difficulties/developmental delay
What cardiac defects might be present in DiGeorge syndrome?
- Tetralogy of Fallot
- Interrupted aortic arch
- Ventricular septal defect
- Truncus arteriosus
Give an example of a palatal abnormality that may be present in DiGeorge syndrome
Cleft palate
What immune deficiencies may be present in DiGeorge syndrome?
- Impaired T-cell production and function
- Thymic hypoplasia
Who is at particularly high risk of hypocalcaemia in DiGeorge syndrome?
Neonates
What causes hypocalcaemia in DiGeorge syndrome?
Parathyroid dysfunction
What is the chromosomal abnormality in Williams syndrome?
Deletion of a region of chromosome 7q11.23
What gene is contained within chromosome 7q11.23?
Elastin gene
Is Williams disease inherited or de novo?
Usually de novo
How does Williams disease often present?
Poor feeding and hypocalcaemia as a neonate
What is the result of elastin deletion in Williams syndrome?
Arteriopathy
What arteries are affected in Williams syndrome?
Can affect any artery
What is the characteristic arteriopathic lesion in Williams syndrome?
Supra-valvular aortic stenosis
What are the characteristic facial features of Williams syndrome?
- Puffy etes
- Long philtrum
- Stellate iris
How does Williams syndrome present cognitively?
- Moderate learning difficulties
- Chatty demeanour and overfriendliness
