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Flashcards in Genetics Deck (54)
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Define Lyonization

Inactivation of one X chromosome


Horizontal transmission is characteristic of what type of inheritance?

Autosomal recessive. Multiple affected family members in same generation but none in other generations. Males and females equally affected.


What is the carrier frequency of PKHD1 gene that leads to autosomal recessive kidney disease?



What is incidence of autosomal recessive kidney disease?

1:20 000


What type of inheritance does this pedigree demonstrate?

What are the characteristics of this type of inheritance?

Autosomal Dominant


  1. Vertical pattern of transmission
  2. Can appear in multiple generations
  3. 50% recurrence risk
  4. Males and females equally affected
  5. Male-to-male transmission (can occur with y linked also, but rare)


What is incomplete penetrance

Carrying mutation without phenotypic manifestations. Can appear as a skipped generation.


What is variable expression?

Manifesting a disorder to varying degrees.


What is a somatic mutation?

Spontaneous genetic mutation in a cell in the developing embryo.


A karyotype with too many, or too few chromosomes where the total is not a multiple of 23.



What syndrome does this girl have and what are the features?

  1. 1:2500
  2. Normal intelligence
  3. Streak ovaries - failure of menstruation, low oestrogen, high gonadotrophins and infertility.
  4. Normal secondary sexual characteristics may develop normally or be induced with oestrogens.
  5. Uterus is usually normal and pregnancy possible with donated ova.
  6. Short stature throughout childhood with failure of pubertal growth spurt.
  7. Webbed or short neck
  8. Low hairline
  9. Shield chest with wide spaced nipples
  10. Cubitus valgus
  11. Cardiovascular abnormalities (esp aortic coarc in 10-15%)
  12. Renal anomalies (horseshoe, duplicated ureters, aplasia) in 1/3
  13. Non pitting lymphoedema on 1/3


Features of triple x syndrome

  1. 1:1000 live-born girls 
  2. Little phenotypic abnormality but tend to be tall
  3. Intelligence in normal or low-normal range but reduced cf siblings
  4. Mild developmental and behavioural difficulties are more common.
  5. Fertility normal
  6. Increased incidence of early menopause


Features of Klinefelter syndrome (47,XXY)

  1. 1:600 live-born boys
  2. Phenotypic abnormalities rare prepubertally
  3. Tend to be tall
  4. Spontaneous expression of secondary sexual characteristics is variable
  5. Poor growth of facial and body hair  
  6. Testes are small & assoc w/ azoospermia
  7. Testosterone production is around 50% of normal and gonadotrophins are raised.
  8. Gynaecomastia in 30%
  9. Increased risk of male breast cancer
  10. Female distribution of fat and hair and high pitched voice common but not typical.
  11. Intelligence in normal or low-normal range but reduced cf siblings
  12. Mild developmental and behavioural problems are more common.


Phenotypic features of Trisomy 21

  1. Brachycephaly
  2. Eyes - upslanting palpebral fissures, epicanthic folds, Brushfield spots on the iris
  3. Protruding tongue
  4. Hands - single palmar crease, fifth finger clinodactly
  5. Feet - wide sandal gap b/w first and second toes
  6. Hypotonia
  7. Moderate learning difficulty


Genetics of trisomy 21

  1. 1 in 700 live births
  2. Secondary to meotic non dysjunction during oogenesis, more common with increasing maternal age
  3. 3% have detectable mosaicism usually resulting in milder phenotype


Common systems problems in trisomy 21

  1. Cardiovascular malformations 40%, esp AV septal defects
  2. GI abnormalities 6%, esp duodenal atresia and Hirschprungs Disease
  3. Haem abnormalities esp ALL, AML and transient leukaemias.
  4. Hypothyroidism
  5. Cataracts in 3%
  6. Alzheimer's disease in majority by 40 years.


What are features of the microdeletion syndrome 22q11?

AKA DiGeorge syndrome

  1. Parathyroid gland hypoplasia with with hypocalcaemia
  2. thymus hypoplasia with t-lymphocyte deficiency
  3. congenital cardiac malformations esp interrupted aortic arch and truncus arteriosis
  4. cleft palate
  5. learning disability
  6. Increased incidence of psychiatric disorders esp schizophrenia

Remember CATCH-22

Cardiac Abnormality (esp TOF)
Abnormal facies
Thymic aplasia
Cleft palate


Williams syndrome is due to microdeletions involving the elastin gene on chromosome 11. What are the features of this syndrome?

  1. Supravalvular aortic stenosis
  2. Hypercalcaemia
  3. Stellate irides
  4. Learning disability
  5. Characteristic facial appearance



What is this syndrome and what are the characteristic facial features?

Williams Syndrome

  • Sunken nasal bridge
  • Periorbital puffiness
  • Epicanthic folds visible
  • Stellate irides
  • Long philtrum
  • Small and widely spaced teeth
  • Wide mouth
  • Prominent lower lip
  • Small chin


What is the risk of having another child with trisomy 21?

  • 1% above maternal age related risks
  • Age 36, background risk is 0.5%
  • Parents with a Robertsonian translocation involving chromosome 21 have a much higher recurrence risk.


Mutations in the tumor suppressor gene APC (adenomatous polyposis coli) may result in what?

Familial adenomatous polyposis and potentially Colorectal CA


A mutation to the gene NF1 on the long arm of chromosome 17 is likely to result in which disorder?

Neurofibromatosis type 1. NF1 causes non cancerous lumps. Often assoc w/ scoliosis, learning difficulties, eye problems and epilepsy.


p53 is located on the short arm of chromosome 17. What is the significance of this gene?

Known as the "guardian of the genome" p53 is a tumour suppressor protein which regulates the cell cycle. More than 50% of human tumours have a mutation or suppression of p53.


How does the RB1 protein on 13q14.1-14.2 prevent excessive cell growth?

RB1 is a tumour suppressor gene that inhibits cell cycle progression until the cell s ready to divide. Mutation in this gene results in retinoblastoma.

Other cancers associated with mutations in this gene include bladder cancer, lung cancer, breast cancer, osteosarcoma, melanoma.


A loss of function mutation of the RET proto-oncogene results in what disease?

Hirschprungs disease


A gain of function mutation of the RET proto-oncogene results in what disease

  • MEN 2a& 2b carcinomas
  • Medullary thyroid carcinoma
  • Phaeochromocytoma
  • Parathyroid hyperplasia


What is this syndrome and what are the typical facial features?

Fragile X

1. Relative macrocephaly (head circumference >50th percentile for age and sex)

2. Strabismus

3. Pale blue irises

4. Midface hypoplasia with sunken eyes

5. Prominent forehead and jaw


Noonan syndrome is an autosomal dominant disorder that has a birth incidence of 1 in 1000-2500 live births. It may present in utero with fetal nuchal oedema.

What are the main features of Noonan Syndrome?

  • Short stature
  • Short neck with webbing or redundancy of skin
  • Facial dysmorphism
  • Characteristic chest deformities - pectus carinatum superiorly and pectus excavatum inferiorly, broad chest with wide spaced nipples
  • Self-limited feeding problem (25%)
  • Cryptorchidism
  • Learning difficulties
  • Cardiac
  • Bleeding diathesis
  • Leukemia
  • Neuroblastoma
  • Non-Hodgkins Lymphoma


This child has an autosomal dominant syndrome and on presentation has short stature, a webbed neck, a cardiac murmur and pectus carinatum. 

What is the syndrome and what are the classic facial features?

Noonans Syndrome

  • Hypertelorism
  • Broad forehead
  • Ptosis
  • Down-slanting eyes in infancy
  • epicanthic folds
  • posteriorly rotated ears
  • Characteristic cupids bow upper lip


This boy has atresia choanae and genital hypoplasia. He has been found to have a new mutation of the CHD7 gene on chromosome 8. What sydrome does he have and what are all the features of this syndrome?

CHARGE Syndrome

C - Colobomas

H - Heart malformations

A - Atresia of the choanae

R - Retardation of growth and development

G - Genital hypoplasia

E - Ear abnormalities (of pinna, deafness)

Cleft lip/palate abnormalities are also common.


This girl was found to have icteric sclera and posterior embryotoxon. You diagnose her with an autosomal dominant syndrome which results from deletions or mutations in the JAG1 gene on chromosome 20.

What is her diagnosis and what are the features of this syndrome?

Alagille Syndrome.

  • Hepatic - cholestatic jaundice, paucity of intrahepatic bile ducts
  • Cardiac - peripheral pulmonary stenosis +/- complex malformations
  • Eye - posterior embryotoxon (image shown), abnormalities of the anterior chamber
  • Vertebral - butterfly vertebrae, hemivertebrae, rib anomalies