1. Meiotic nondisjunction (94%) - Error at meiosis - Related to maternal age 2. Translocation (5%) - Robertsonian translocation - a part of 21 is attached to another chromosome, usually 14 - One parent may be a carrier 3. Mosaicism (1%) - Some cells are normal, some have trisomy 21

Genetics Flashcards by Hedda Moen

Clinical features in Trisomy 21

Hypotonic
Flat occiput
Single palmar creases
Incurved fifth finger
Wide ‘sandal’ gap between the big and second toes

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Complications in Trisomy 21

Learning difficulties
Congenital heard disease (present in 40%) - ECD (endocardial cushion defect (AV-canals)
Duodenal atresia
Impairment of vision (cataract) and hearing (secretory otitis media)
Hypothyroidism
Coeliac disease
Atlantoaxial instability
Epilepsy
Early onset Alzheimer disease

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Causes of Trisomy 21

Meiotic nondisjunction (94%)
- Error at meiosis
- Related to maternal age
Translocation (5%)
- Robertsonian translocation - a part of 21 is attached to another chromosome, usually 14
- One parent may be a carrier
Mosaicism (1%)
- Some cells are normal, some have trisomy 21

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What are the typical craniofacial appearance in Down’s?

Round face and flat nasal bridge
Upslanted palpebral fissures
Epicanthic folds
Brushfield spots in iris
Small mouth and protruding tongue
Small ears
Flat occiput and third fontanelle

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What genetical abnormality is Edwards syndrome?

Trisomy 18

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Clinical features of Edwards syndrome

Low birthweight
Prominent occiput
Small mouth and chin
Short sternum
Flexed, overlapping fingers
‘Rocker-bottom’ feet
Cardiac and renal malformations

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What genetical abnormality is Patau syndrome?

Trisomy 13

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Clinical features of Patau syndrome?

Structural defect of brain
Scalp defect
Small eyes (microphthalmia) and other eye defects
Cleft lip and palate
Polydactyly
Cardiac and renal malformations

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Genetics in Turner syndrome

45, X

50% have one X
The others have deletion of the short arm of one X chromosome - isochromosome

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Clinical features of Turner syndrome

Short stature!
Lymphedema of hands and feet
Neck webbing or thick neck
Cubitus valgus
Widely spaced nippels
CHD - coarctation of the aorta
Delayed puberty
Infertility
Hypothyroidism
Normal intellect

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Treatment of Turner syndrome

Growth hormones

- Oestrogen therapy

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Genetics in Klinefelter syndrome

47, XXY

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Clinical features of Klinefelter syndrome

Tall stature!
Infertility
Hypogonadism with small testes
Gynecomastia in adolescence
Usually normal intelligence

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Examples of syndromes caused by deletion

Cri-du-chat syndrome - deletion on chromosome 5
DiGeorge syndrome - deletion on chromosome 22
Williams syndrome - deletion on chromosome 7

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What is mendelian inheritance?

Transmission of inherited traits or diseases caused by variation in a single gene

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Examples of X-linked recessive disorders

Colour blindness
Duchenne and Becker muscular dystrophies
Fragile X syndrome
G6PD deficiency
Haemophilia A and B
Hunter syndrome

How can the Fragile X syndrome affect females?

40-50 % of female carriers have learning difficulties - usually mild to moderate

How many repeats is normalen, ‘premutation’ and ‘full mutation’ in fragile X syndrome?

Normal = about 45 repeats
‘Premutation’ = 55-200 repeats (males can be unaffected but transmit condition further to grandsons)
‘Full mutation’ = >200 repeats

What is the most common genetic cause of learning difficulties?

Down syndrome - most common

2. Fragile X syndrome - second most common

Clinical features in Fragile X syndrome

Moderate - severe learning difficulties
Macrocephaly
Macroorchidism - postpubertal
Facies: long face, large everted ears, prominent mandible, broad forehead
Mitral valve prolapse
Joint laxity
Scoliosis
Autism, hyperactivity

What does imprinting mean?

Expression of some genes is influences by the sex of the parent who transmitted it.

The genetics of Prader-Willi syndrome

Absence of the functional paternal copy at the region 11 - 13 on chromosome 15
- Paternal chromosome responsible

The genetics of Angelman syndrome

Absence of the functional maternal copy at the region 11 - 13 on chromosome 15
- Maternal chromosqme responsible

Clinical features of Prader-Willi syndrome

Obesity - increased feeding and weight - binge eating
Short stature, small hands and feet
Hypotonia
Developmental delay, mild to severe mental retardation
Hyperphagia

Clinical features of Angelman syndrome

- Severe cognitive impairment - Characteristic facial appearance - Inappropriate laughter - Ataxia and jerky arm movements - 'Happy Puppet syndrome' - Epilepsy

VACTERL association

``` V - Vertebral anomalies A - Anal atresia C - cardiac defects TE - trecheoesophageal fistula R - renal anomalies L - limb defects (radial) ```

Noonan syndrome

- Autosomal dominant - Turner phenotype: * Characteristic facies * Mild learning difficulties * Short webbed neck with trident hair line * Pectus excavatum * Short stature - CHD - PULMONARY STENOSIS, atrial septal defect

Pulmonic stenosis is common in which syndromes?

- Noonan syndrome | - Alagille syndrome

Williams syndrome

- Deletion on chromosome 7 - Clinical features: * Short stature * Face: Elfin facies * Transient neonatal hypercalcemia * CHD - Supravalvular aortic stenosis * Mild to moderate learning difficulties

Endocardial cushion defect is common in which syndrome?

Trisomy 21 - Down's syndrome

Aortic stenosis is common in which syndrome?

Williams syndrome - supravalvular aortic stenosis

Coarctation of aorta is common in which syndrome?

Turner syndrome

Truncus arteriosis is associated with which syndrome?

CATCH-22 --> DiGeorge syndrome Also seen: * Transposition of the great arteries * Aortic arch abnormalities

Mitral valve prolapse is common in which syndromes?

- Marfan syndorme | - Ehlers-Danlos syndrome

CATCH-22 mnemonic

``` C - Cardiac A - Abnormal facies T - Thymic hypoplasia C - Cleft palate H - Hypocalcemia (hypoplasia of parathyroid) 22 - micro deletion on chromosome 22 * DiGeorge syndrome * Velocardial-facial syndrome * Conotruncal anomaly face syndrome ```