WEEK 7 (Klinefelter and Turner syndromes)

Question 1

What is Klinefelter syndrome and what are the symptoms?

Answer 1

Kilinefelter syndrome is when boys are born with an extra X chromosome (XXY). To compensate for the extra x chromosome, on X chromosome will be inactivated (Barr body).

SYMPTOMS:
- Taller than average stature.
- Longer legs due to delayed epiphyseal closure which leads to increased long bone length
- Absent, delayed or incomplete puberty.
- After puberty, less muscle and less facial and body hair compared with other teens.
- Small, firm testicles (Testicular atrophy)
- Small penis.
- Enlarged breast tissue (gynecomastia)
- Abnormal Leydig cell function - decrease testosterone and increase LH and oestrogen

Question 2

What is Turner syndrome and what are the symptoms?

Answer 2

Turner syndrome, a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing (XO).

Sex chromosome (X, or rarely Y) is loss often due to nondisjunction during meiosis or mitosis. Meiosis errors usually occur in paternal gametes (sperm missing the sex chromosome) and Mitosis errors occur after zygote formation (loss of sex chromosome in some but not all cells).

SYMPTOMS:
- Short stature (SHOX gene, preventable with growth hormone therapy)
- lymphatic defects resulting in webbed neck
- 1st degree amenorrhea (late period)
- menopause before even starting period (pregnancy is possible using IVF & progesterone)
- decrease in oestrogen leads to increase in LH & FSH)

Question 3

What is Double Y syndrome and what are the symptoms?

Answer 3

Double Y syndrome is a chromosomal mutation in which boys have an extra Y chromosome (XYY)

Frequency: 1 in 250 males

SIGNS AND SYMPTOMS:
- Phenotypically normal (usually undiagnosed)
- Very tall
- Normal fertility
- May be associated with severe acne
- Often less than average IQ
- Learning disabilities & autism spectrum disorders
- High levels of male hormones
- Delayed speech and language skills

Question 4

Define ‘Aneuploidy’

Answer 4

Aneuploidy is an abnormal number of chromosomes such as having a single extra chromosome (47) or a missing (45)

Question 5

What are the 5As of Down syndrome?

Answer 5

• Advanced maternal age
• Atresia (duodenal)
• Atrioventricular septal defect
• Alzheimer disease (early onset)
• AML/ALL

Question 6

______________ is the most common viable chromosomal disorder and most common cause of genetic intellectual disability

Answer 6

Down Syndrome

Question 7

How is Down syndrome diagnosed?

Answer 7

The first trimester ultrasound commonly shows increased nuchal translucency and hypo plastic nasal bone.

markers for Down syndrome are increased hCG and increased inhibin

Question 8

What are the causes of Down syndrome?

Answer 8

• 95% of cases due to meiotic nondisjunction (most commonly during meiosis)
• 4% of cases due to unbalanced Robertsonian translocation (most typically between chromosomes 14 and 21)
• 1% of cases are due to post fertilisation mitotic error

Question 9

What are the symptoms/causes of Down syndrome?

Answer 9

• Intellectual disability
• A single line across the palm of the hand (palmar crease)
• Flat faces
• Almond-shaped eyes that slant up.
• Hirschsprung disease
• Congenital heart disease
• Associated with early-onset of Alzheimer disease (chromosome 21 codes for amyloid precursor protein)

Question 10

What is Edwards syndrome and what are the symptoms?

Answer 10

Babies with Edwards’ syndrome have more of chromosome 18 in some or all of the cells in their body. It is also known as Trisomy 18.

SYMPTOMS:
- Prominent occiput
- Rocker-bottom feet
- Intellectual disability
- Nondisjunction
- Clenched fists with overlapping fingers
- Low-set ears
- Micrognathia (small jaw)
- Congenital heart disease
- Death usually occurs by age 1

Question 11

What is Patau syndrome (trisomy 13) and what are the symptoms?

Answer 11

Patau’s syndrome is a serious rare genetic disorder caused by having an additional copy of chromosome 13 in some or all of the body’s cells. It’s also called trisomy 13.

SIGNS AND SYMPTOMS:
- severe intellectual disability
- rocker-bottom feet
- micropthalmia (one or both of a baby’s eyes are small)
- cleft lip/palate
- holoprosencephaly (results in abnormal development of the brain)
- polydactyly
- cutis aplasia
- congenital heart disease
- polycystic kidney disease
- Death usually occurs by age 1
- Defect in fusion of prechordal mesoderm -> midline defects

Question 12

What is the main cause of Aneuploidy (an abnormal number of chromosomes)?

Answer 12

Nondisjunction