Genetic disorders

Dr. Ishrag Abdelwahab

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