Chromosomal abnormalities.

Valmiki Seecheran.Year V | MBBS.

Introduction.

• A chromosome anomaly/ mutation is a missing, extra or irregular portion of chromosomal DNA.

• Error usually occurs in cell division following meiosis/ mitosis.

Common types.

• Down’s syndrome.• Turner’s syndrome.• Patau’s syndrome.• Edward’s syndrome.

Down’s syndrome – Trisomy 21.

• Mental abilities similar to a 8-9 year old. – IQ (50-70).

• Poor immune function.• Developmental delays.• Increased risk of: – CHD. – ASD & VSD (80%).– Leukaemia. –Up to 15x more common. (ALL & AML).– Thyroid disorders. – Hypothyroidism (50%)– Mental illnesses.

Epidemiology.

• 1 per 1000 births.

Down’s syndrome – Trisomy 21.

Down’s syndrome – Trisomy 21.

Screening.

• All pregnant women should be screen regardless of age.

• Can be used in combination to increase detection rate.

• Amniocentesis/ chorionic villous sampling is required to confirm diagnosis.

• Screening in 1st and 2nd trimester is better than just screening in 1st trimester.

Screening.

Diagnosis.

• Based on physical appearance at birth.• Chromosomal analysis to determine if

translocation is present and also help predict the risk of the child’s parent with future offspring.

Management

• Physicians & parents should be aware of the range of psychomotor potential.

• Usual immunizations should be performed.• Surgical management of associated conditions

should be provided.• Regular screening is necessary to diagnose

epilepsy, hypothyroidism, auditory and visual loss.

Turner’s syndrome.

• 45,X - absence of an entire sex chromosome, Barr body.

• 1 in 2000, 1-500 phenotypic females.• Short stature, low-set ears, webbed necks.• Girls experience gonadal dysfunction –

amenorrhea & sterility.• CHD, hypothyroidism, diabetes, auditory-

visual problems and auto-immune diseases.

Turner’s syndrome.

Kleinfelter vs. Turner’s syndrome.

Diagnosis.

• Postnatal.– Diagnosed at birth due to heart problems,

unusually wide neck or swelling of hands and feets.– Undeveloped puberty.

• Prenatal.– Amniocentesis or chorionic villus sampling.– Abnormal ultrasound findings – heart defect,

kidney abnormality, hygroma, ascites.– Triple/quadruple maternal serum screen.

Treatment.

• Most people live long and healthy lives.• Growth hormone/estrogen replacement

therapy are usually required.• High risk of keloid formations – cosmetic

surgery.• Multi-disciplinary team for screening –

cardiologist, endocrinologist, nephrologist, psychologist.

Patau’s syndrome. (Trisomy 13)

• Some/ all of the cells contain extra genetic material from chromosome 13.

• Nondisjunction of chromosomes during meiosis.

• 1 in 10,000.

Patau’s syndrome. (Trisomy 13)

Patau’s syndrome. (Trisomy 13)

• Other.– VSD/PDA.– Dextrocardia– Single umbilical artery.

• Urogenital.– Abnormal genitalia.– Kidney defects.

• MBJ.– Polydactyly.– Low set ears.– Cyclopia.– Cleft palate.

• CNS.– Microcephaly.– Meningomyelocele.– MR/motor disorder.– Holoprosencephaly (failure of the forebrain to divide)

Diagnosis.

• Based on clinical findings.• Fetal chromosome testing will show trisomy

13.• Quad screen does not provide reliable means

of screening.

Treatment & Prognosis.

• Case-by-case basis and depends on individual circumstances.

• More than 80% of children die within first year of life.

• Surgery may be necessary to repair heart defects or cleft lip/palate.

• Physical/occupational and speech therapy will help individuals maximise their potenial.

Edward’s syndrome. Trisomy 18.

• Presence of all or part of an extra 18th chromosome in cells.

• Nondisjunction during meiosis.• 1 in 6000 – most are females (80%).• Low rate of survival – heart abnormalities,

kidney malformations.

Signs & Symptoms.

• VSD, ASD, PDA.• Omphalocele – intenstines protruding outside

the body.• Esophegeal atresia.• MR – developmental delyas.• Feeding difficulties.• Arthrogryposis (multiple joint contractures at

birth).

Signs & Symptoms.

• Similar to Patau’s.

• Microcephahly• Micrognathia (small jaw).• Cleft lip/palate.• Narrow eyelid folds – palpebral fissures.• Ocular hypertelorism – wide space eyes.• Undeveloped fingers/ nails.• Clubfoot/ Rocker-bottom foot.• Undescended testicles.• Choroid plexus cysts – pockets of fluid on the brain.

Treatment.

• Supportive.• Treat infections as appropriate. Sepsis is a

continuous concern.• Nasogastric/gastrostomy supplmentation for

feeding problems.• Multifaceted team – cardiologist, neonataologist,

ophthalmologist, orthopaedist, psychologist, speech language pathologist,

• Genetic counselling.

Thank you.