Turner syndrome is a chromosomal disorder affecting females. It occurs when there is a complete/partial absence of the second X chromosome resulting in the 45,X karyotype.
Pathophysiology
Turner syndrome occurs sporadically with no known risk factors. There are rare cases where an X chromosome deletion may be passed from mother to daughter.
An X chromosome is necessary for embryogenesis. An absent X chromosome (monosomy Y) is not compatible with life. Monosomy X is the most common form of Turner syndrome. Males who lose their Y chromosome usually lose the Y chromosome late in development, such that they have completed most of their development at this stage but they may have some features of Turner syndrome (such as short stature, infertility, cardiovascular diseases and delayed puberty).
Turner syndrome occurs due to nondisjunction during meiosis or mitosis. Depending on when this nondisjucn
There are no known risk or causative factors for Turner syndrome. It is sporadic in occurrence except for rare cases in which a small X chromosome deletion may be passed from mother to daughter.
What happens in Turner syndrome a chromosomal nondisjunction during meiosis or mitosis. Nondisjunction is the phenomenon where chromosomes fail to separate properly, leading to an unequal distribution of chromosomes in daughter cells.
Let’s discuss the difference between meiotic vs mitotic nondisjunction:
- Meiotic nondisjunction - this leads to complete sex chromosomal monosomy (45,X)
- Mitotic nondisjunction - leads to variation in which some cells have the 45,X karyotype while other have the normal female karyotype (45,XX). It leads to a mild phenotypic expression.
😷 Presentation
- Musculoskeletal abnormalities:
- ⭐️ Shield chest - broad chest with widely spaced nipple
- ⭐️ Webbed neck - also seen in Noonan syndrome.
- ⭐️ Short stature - due to the presence of only one copy of the SHOX (short stature homeobox) gene.
- Cubitus valgus - forearm is angled away from the body to a greater degree than normal when fully extended.
- Short fourth metacarpals & metatarsals and nail dysplasia
- Osteoporosis
- Sexual development:
- ⭐️ Primary ovarian insufficiency - patients with Turner syndrome have streak ovaries (a form of ovarian dysgenesis) and so their ovaries are non-functional.
- Delayed puberty
- Primary amenorrhoea
- Infertility - spontaneous pregnancy is possible but extremely rare.
- Cardiovascular abnormalities:
- ⭐️ Coarctation of the aorta - with brachial-femoral delay
- ⭐️ Aortic dissection and rupture
- Bicuspid aortic valve - which increases the risk of aortic stenosis.
- Hypertension
- Lymphatic abnormalities:
- ⭐️ Cystic hygromas
- Lymphoedema of the hands and feet in the neonatal period
Other features of Turner syndrome include:
- High arched palate
- Low-set posterior hairline
- Gonadoblastoma - especially in patients with 45,XO/46,XY mosaicism.
- Malformations of the kidney and ureters - especially horseshoe kidney.
🔍 Investigations
This diagnosis requires high clinical suspicion.
- Blood tests:
- Blood tests may indicate hypergonadotrophic hypogonadism - this is when the gonadotrophic hormones are elevated (FSH and LH) while the hormones from the gonads themselves are suppressed (oestrogen and androgens).
- 🏆 Karyotype - this is the gold standard and must show at least 10% of the cells with a complete or partial loss (in the cases of mosaic Turner syndrome) of a sex chromosome.
💡 As patients with Turner lack a second X chromosome, they should also be evaluated for X-linked recessive conditions once a diagnosis is established.
🧰 Management
There is no way to treat the underlying genetic cause of Turner syndrome. Treatment aims to help with the complications of the condition:
- Growth hormone therapy - to prevent short stature.
- Oestrogen and progesterone - to help establish female secondary sex characteristics, regulate the menstrual cycle and prevent osteoporosis.
- Fertility treatment - to increase the chances of becoming pregnant.
- Surgical removal of streak ovaries
- Complication monitoring
🚨 Complications
- Type 2 diabetes mellitus
- Crohn's disease
- Hashimoto thyroiditis
- Grave’s disease
- Infertility
- Hearing loss
- Osteoporosis
- Hypertension
- Gonadoblastoma