Chromosomal microdeletion disorders Di George Syndrome: Congenital Heart Disease Palatal abnormalities Thymic/Parathyroid Hypoplasia Characteristic Facies Learning Difficulties Commonest microdeletion disorder Approx 1/4000 live births Trisomy - gain of one chromosome can be tolerated Trisomy 21 Down Syndrome. Approx 1 in 700 incidence. Strong correlation between incidence and – maternal age. Clinical features: Newborn period - severe hypotonia (lack of muscle tone), sleepy, excess nuchal skin Craniofacial macroglossia (enlarged tongue), small ears, epicanthic folds, upward sloping – palpebral fissures, Brushfield spots (spots on iris) Limbs single palmar crease, wide gap between first and second toes – Cardiac - A and V septal defects Other - short stature, duodenal atresia (duodenum not properly developed). 95% are trisomy: 90% of which is extra chromosome from mother and 5% from meiotic nondisjunction. 4% caused by translocation, and 1% from mosaicism from mitotic nondisjunction. Tetrasomy - gain of two chromosomes can be tolerated Loss of a chromosome gives a 50% reduction in fully expressed gene products, gain of a chromosome gives a 33% increase. Partial Aneuploidy translocations, can be balanced or unbalanced. – Structural translocations, deletions, insertions, inversions, rings. – Mosaicism different cell lines –
Chromosomal microdeletion disorders Di George Syndrome: Congenital Heart Disease Palatal abnormalities Thymic/Parathyroid Hypoplasia Characteristic Facies Learning Difficulties Commonest microdeletion disorder Approx 1/4000 live births Trisomy - gain of one chromosome can be tolerated Trisomy 21 – Down Syndrome. Approx 1 in 700 incidence. Strong correlation between incidence and maternal age. Clinical features: Newborn period - severe hypotonia (lack of muscle tone), sleepy, excess nuchal skin Craniofacial – macroglossia (enlarged tongue), small ears, epicanthic folds, upward sloping palpebral fissures, Brushfield spots (spots on iris) Limbs – single palmar crease, wide gap between first and second toes Cardiac - A and V septal defects Other - short stature, duodenal atresia (duodenum not properly developed). 95% are trisomy: 90% of which is extra chromosome from mother and 5% from meiotic nondisjunction. 4% caused by translocation, and 1% from mosaicism from mitotic nondisjunction. Tetrasomy - gain of two chromosomes can be tolerated Loss of a chromosome gives a 50% reduction in fully expressed gene products, gain of a chromosome gives a 33% increase. Partial Aneuploidy – translocations, can be balanced or unbalanced. Structural – translocations, deletions, insertions, inversions, rings. Mosaicism – different cell lines