Learning objectives Basic knowledge • Modes of inheritance • Common genetic disorders • Management • Basic knowledge in genetics Gene is a specific sequence of nucleotide in DNA or RNA that is located usually on a chromosome and that is functional unit of inheritance. Each somatic cell has 46 Chromosomes (22 pairs of autosomes and one pair of sex chromosome) germ cells contain 22 autosomes and 1 sex chromosome, for a total of 23. Most of the genetic material is contained in the cell's nucleus. The mitochondria contain their own unique genome All mitochondria are maternally derived b/c sperm do not carry mitochondria into fertilized eggs. Mode of inheritance Single gene disease: Autosomal recessive Autosomal dominant X-linked recessive X-linked dominant Mitochondrial chromosomal abnomality in down syndrome ,turner syndrome ,klinefelter syndrome ,digorge syndrome Multifactorial diseases such as cleft palte that run in families,asthma Autosomal recessive (AR) The affected individual has two carrier parents • If both parents are carrier then their children have • 50% chance to be carrier 25% chance to be diseased 25% chance to be normal Male : female is 1:1 Examples: SCA, thalassemia ,CF, most of metabolic • diseases. Autosomal dominant (AD) The condition is inherited from one affected parent • If one of the parent affected then his or her • children have : 50% chance to be affected 50% chance to be normal Male : female is 1:1 Examples: achondroplasia, NF ,T.S ,hereditary • spherocytosis X-linked recessive Males are affected • This because the abnormal gene is on an X chromosome • Females are carrier. Remember lyonisation. • If the mother is carrier then her children : • If males have 50% chance to be affected and 50% chance to be normal. If females have 50% chance to be carrier and 50% chance to be normal. Examples: Duchenne muscular dystrophy ,G6PD • deficiency,haemophilia A X-linked dominant Extremely rare • Males and females are affected • Affected female pass the condition to half of her • the offsprings regardless to their sex Affected male pass the condition on to all his • daughters and none of his son These condition usually lethal to male • Examples: rett's syndrome , vit D resistant rickets, • incontinentia pigmenti . Mitochondrial disorders Mitochondrial disorders exhibt maternal inheritance • Affect brain ,muscles , heart and liver. • Common presentations : • Developmental delay Myopathy Encephalopathy Seizures Cardiomyopathy Down syndrome
Incidence 1:800 live birth •
Risk increase with maternal age • Clinical features: • Facial feature: brachycephaly, delayed closure of A.F., upward slanting eyes, epicanthic folds, cataract, brushfield spots ,low set ears ,hearing defect mainly conductive hearing loss,protruded tongue Hand: short broad fingers ,single palmar crease , clinodactyly Feet: sandal sign Developmental delay ,hypotonia &intellectual retardation Down syndrome There is increase risk of: Congenital heart disease :esp. AVSD===>esimenger syndrome GIT anomlies:doudenal atresia (double bubble sign in x ray), annular pancreas, hirschsprung disease. Atlantoaxial subluxation Acute leukaemia Alzheimer disease There is risk of recurrent chest infection?? Diagnosis of genetic disorders Hx • Ex • Investigation: • Neonatal Screening for genetic disorders Karyotyping for chromosomal abnormalities Specific enzyme assay ,Hb electrophoresis...depends on the disease. Management of genetic disorders Depends on the condition. • Genetic counselling. • Thanks