Klinefelter’s Syndrome

This is a condition which leads to an additional sex chromosome, giving the karyotype 47 XXY

– The offspring will be male due to the presence of the Y chromosome but will have deformities

Management:

– Testosterone replacement hormone therapy

– Infertility treatment (e.g., ICSI or IVF) used to help them produce offspring

– Breast removal surgery due to risk of breast cancer

Turner’s Syndrome

This is a condition which leads to a missing chromosome, giving the karyotype 45XO

– As there is no Y chromosome, these individuals are female and with have female sexual organs

Inheritance:

Either due to presence of only one sex chromosome (X) or deletion of the short arm of one of the X chromosomes

Symptoms:

– Antenatal –> Early miscarriage, foetal hydrops and cystic hygroma

– Body –> Short stature and many pigmented naevi

– Head and Neck –> Webbed neck, high-arched palate

– Chest –> Widely spaced nipples, shielded chest

– Limbs –> spoon-shaped nails, lymphoedema

– Heart –> bicuspid aortic valve, aortic coarctation

– Ovaries anomalies –> ovarian dysgenesis giving amenorrhea in puberty

Complications:

– Endocrine –> primary amenorrhoea, hypothyroidism

– Autoimmune –> increases risk of Crohn’s disease

– Infertility (due to ovarian dysgenesis)

Diagnosis:

– Can be diagnosed karyotyping antenatally (by amniocentesis or CVS) or postnatally

Management:

No cure available, management focussed on treating the symptoms

– Growth hormone replacement

– Oestrogen replacement (for the development of secondary sexual characteristics) 

Swyer Syndrome

This is a rarer condition in which there is a mutation in the SRY gene on the Y chromosome.

– This gene is needed for the masculinisation of the embryo. Without it, the indifferent gonads fail to differentiate into testicles in an XY fetus

– As such, this means that these XY individuals develop as females with a uterus, fallopian tubes, vagina etc.

– Therefore, people with Swyer syndrome are born with the normal appearance of female, but they have non-functional gonads.

– This leads to problems in puberty as the gonads will not make oestrogen, so they do not have breast growth and menstrual periods

Management:

Oestrogen and Progestogen hormone replacement therapy

Noonan syndrome

This is a condition which is referred to as the male version of Turner’s syndrome. However, unlike Turner’s syndrome the mutation is not on one of the sex chromosomes – instead it is an autosomal dominant condition

Inheritance:

An autosomal dominant condition due to mutation in gene (usually PTPN11) on Chr 12

Symptoms:

– Head and neck –> Low-set ears, triangle shaped face, large head with excess skin on back of neck

– Eyes –> Hypertelorism (widely spaced eyes)

– Skin –> lymphedema

– Body –> webbed neck, short, wide space between the nipples (resembling Turner syndrome)

– Heart abnormalities –> Pulmonary valve stenosis

Management:

MDT approach to manage symptoms according to system affected