Down Syndrome (trisomy 21 )

Introduction:•Down syndrome is the most common chromosome abnormality in humans.• It is typically associated with a delay in cognitive ability (mental retardation) and physical growth, and a particular set of facial characteristics.•The average IQ of young adults with Down syndrome is around 50, compared to children without the condition with an IQ of 100.•A large proportion of individuals with Down syndrome have a severe degree of intellectual disability.

Def: is a numerical chromosomal abnormality caused by the presence of a third copy of chromosome 21 (extra chromosme 21).

The extra chromosome causes problems with the way the body and brain develop.

Incidence: 1:700Genetic types:

(95%):Non disjunction

Mosaicism(1%):

Translocation (4%):

•During maternal meiosis[Resluting in ovum with 24 chromosomes (2 chromosomes21 instead of 1)]•IQ is low & it’s mother age dependent.

•The extra chromosome is translocated to another acrocentric chromosome.•IQ is low & it’s not mother age dependent.•One of parents should be translocation carrier.

•Post fertilization event.•IQ is better.

Recurrence risk:

Non disjunction

• Depend on mother age.

• Risk increase with advanced maternal age.

Translocation

• Depend on the chromosome to which the “extra 21” is translocated

• To D- group (1/3 down _1/3 normal_1/3 carrier)

• To chromosome 21 (100% down)

mosaicism

• minimal

Clinical picture:Down syndrome symptoms vary from person to person and can range from mild to severe.

However, children with Down syndrome have a widely recognized appearance.

1-Delayed mental and social development:

Social smile ,Mother recognition, speech delay. Most individuals with Down syndrome have intellectual disability in the mild (IQ 50–70) to

moderate (IQ 35–50) range. Impulsive behavior Poor judgment Short attention span Slow learningN.B Children and adults with DS are at increased risk for developing epilepsy and also Alzheimer's

disease.

2-Delayed motor development: Head support, sitting, crawling, walking, Fine motor skills are delayed. Some children will begin walking at around 2 years of age, while others will not walk until age

four. the development of gross motor skills affection is quite variable.

3-characterstic dysmorphic features:-Head & neck Skull: Brachycephaly, delayed closure of AF, microcephaly Separated joints between the bones of the skull (sutures) Hair: silky Eye: Upward slanting palpebral fissure Medial epicathal fold speckled iris(brushfield iris) Nose: Depressed nasal bridge Flattened nose Ears: Small ears Malformed, over folded helix Underdeveloped ear lobule

Mouth Small mouth Small oral cavity Protruded & fissured Tongue Neck short& broad Excess skin at the nape of the neck

Hands , feet &abdomen Hands short & broad hands clinodactyly (incurved little finger) simian crease (single transverse palmer crease) Feet short & broad feet wide gap between 1st & 2nd toes (sandal gap) Abdomen distention & hernia

4- Associated congenital anomalies:-

a) Cardiac: An atrioventricular septal defect also known as endocardial cushion defect is the most common form with up to 40% of patients affected, This is closely followed by ventricular septal defect that affects approximately 35% of patients.

b) GIT: duodenal atresia , annular pancreas, and imperforate anus. Gastroesophageal reflux disease and celiac disease are also more common among people with DS.

c) Renal anomalies

Complications:a)cardiac: HFb) Increaed risk of leukemia : In particular, acute lymphoblastic

leukemia at least 10 times more common in DS and the megakaryoblastic form of acute myelogenous leukemia is at least 50 times more common in DS.

c)ChestRecurrent chest infection

Leukemia( decreased immunity)

CHD

Hypotonia

d) Thyroid disorders: Low thyroid (hypothyroidism) is most common, occurring in

almost a third of those with DS. This can be due to absence of the thyroid at birth (congenital

hypothyroidism) or due to attack on the thyroid by the immune system.

e) Eye disorders: Almost half have strabismus. Refractive errors, Cataracts, keratoconus ,and glaucoma.

f)Hip problems: risk of dislocationg) Sleep apnea: because the mouth, throat, and airway are narrowedh)Hearing problems: probably caused by regular ear infections.

Diagnosis:-• Down syndrome can be identified in a baby at birth, or even before

birth by prenatal screening.• A doctor can often make an initial diagnosis of Down syndrome at

birth based on how the baby looks. The doctor may hear a heart murmur when listening to the baby's chest with a stethoscope.

Lab:• CBC• Karyotyping : should be done in every patient to determine the

type & recurrence risk Imaging• Echocardiogram to check for heart defects (usually done soon after

birth)• ECG• X-rays of the chest and gastrointestinal tract• Abdominal US ( GIT & Renal anomalies)

Antenatal Diagnosis:Indications:• Old maternal age>35• Previous baby with DS• Family history of translocation

Methods:1- Triple test: done in maternal serum at 15-16 weeks of gestation.• ↓↓α-Fetoprotein• ↓↓ Unconjugated estirol• ↑↑β-hCG (Human chorionic gonadotropin)

Other Serum markers for Down's syndrome:-• Pregnancy-associated plasma protein A (PAPP-A): levels reduced.• Inhibin -A : raised levels.

2-Fetal karyotyping:• Amniocentesis: 14-16 weeks of gestation• Chorionic villus sample: 9-12 weeks of gestation3-Fetal US:• Nuchal translucency ultrasound: thickening of the nuchal fold at

the back of the neck due to delayed drainage of fluid from the upper part of the body

• Short femur ,Cystic hygroma of the neck& dudenal stenosis

Treatment:There is no specific treatment for Down syndrome.TTT of complications:• A child born with a gastrointestinal blockage may need

major surgery immediately after birth. Certain heart defects may also require surgery.

Supportive TTT:• When breast-feeding, the baby should be well supported

and fully awake. The baby may have some leakage because of poor tongue control. However, many infants with Down syndrome can successfully breast-feed.

• Obesity can become a problem for older children and adults. Getting plenty of activity and avoiding high-calorie foods are important.

• Behavioral training can help people with Down syndrome and their families deal with the anger, and compulsive behavior that often occur. At the same time, it is important to encourage independence.

• Special education and training is offered in most communities for children with delays in mental development.

• Speech therapy may help improve language skills.• Physical therapy may teach movement skills. • Special educators are also often needed.

Persons with Down syndrome need to be closely screened for certain medical conditions.

They should have:• Eye exam every year during infancy• Hearing tests every 6 - 12 months, depending on age• Dental exams every 6 months• X-rays of the upper or cervical spine between ages 3 - 5 years [risk

of subluxation of atlantoaxial joint (C1-C2)]• Thyroid testing every 12 months

Prevention:• Genetic counseling for persons with a family history of Down

syndrome .• The risk is significantly higher among women age 35 and older.N.B American College of Obstetricians and Gynecologists recommends offering

Down syndrome screening tests to all pregnant women, regardless of age.

Thank you