Genetics Flashcards
Clinical features in Trisomy 21
- Hypotonic
- Flat occiput
- Single palmar creases
- Incurved fifth finger
- Wide ‘sandal’ gap between the big and second toes
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
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
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
What genetical abnormality is Edwards syndrome?
Trisomy 18
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
What genetical abnormality is Patau syndrome?
Trisomy 13
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
Genetics in Turner syndrome
45, X
- 50% have one X
- The others have deletion of the short arm of one X chromosome - isochromosome
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
Treatment of Turner syndrome
- Growth hormones
- Oestrogen therapy
Genetics in Klinefelter syndrome
47, XXY
Clinical features of Klinefelter syndrome
- Tall stature!
- Infertility
- Hypogonadism with small testes
- Gynecomastia in adolescence
- Usually normal intelligence
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
What is mendelian inheritance?
Transmission of inherited traits or diseases caused by variation in a single gene
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
