Turner Syndrome: A Comprehensive Overview

• Turner syndrome is a chromosomal disorder affecting females, characterized by short stature and underdeveloped ovaries.
• Incidence is 1 in 2000 baby girls.
• It involves having only one X chromosome (45XO).

Aetiology

• Caused by non-disjunction mutation during meiosis.
• It is a sporadic mutation with no known risk factors.
• Up to 50% of cases involve mosaic Turner syndrome (some cells 45XO, some 46XX).

Clinical features

• Short stature is apparent during puberty due to hormone insufficiency.
• Delayed puberty, amenorrhoea, and infertility are caused by primary hypogonadism due to ovarian dysgenesis.
• Systemic manifestations include renal tract abnormalities (horseshoe kidney) and cardiac abnormalities (bicuspid aortic valve, aortic coarctation).
• Other systemic manifestations involve recurrent otitis media, autoimmune diseases (hypothyroidism, type 1 diabetes, coeliac disease).
• Females have good language and reading skills, but potential behavioral and social difficulties.
• Peripheral stigmata include webbed neck, cubitus valgus, broad chest with widely spaced nipples, short 4th digit, scoliosis, low set ears, low posterior hairline, high arch palate, and increased melanocytic naevi.

Differential diagnoses

• Noonan syndrome (autosomal dominant, PTPN11 gene mutation, affects both sexes).
• Other causes of short stature and delayed puberty (e.g., primary ovarian failure, gonadotropin deficiency, functional gonadotropin deficiency).

Investigations

• Bedside: blood pressure, growth assessment, urine dip.
• Laboratory: karyotyping (45XO), blood tests for autoimmune complications, hormone tests (FSH, LH, oestrogen), and metabolic profile.
• Imaging: echocardiogram, renal tract ultrasound, pelvic ultrasound, and DEXA scan.
• Other: pure tone audiometry.

Diagnosis

• Confirmed via karyotyping (45XO).
• May be suspected prenatally via ultrasound findings or in-utero karyotyping through amniocentesis or chorionic villus sampling.

Management

• Hormone replacement therapy:
  • Oestrogen: started at age 11 to trigger puberty, maintain uterus health, and bone density.
  • Progesterone: started after oestrogen to trigger menarche and maintain menstrual cycle.
  • Growth hormone: daily injections from age 5-16 to trigger growth.
• Multidisciplinary management: involving geneticists, endocrinologists, nephrologists, cardiologists, ENT specialists, obstetricians, psychologists, and general practitioners.

Complications

• Autoimmune diseases, recurrent otitis media and glue ear, increased risk of UTIs, osteoporosis, hypertension, higher rates of type 2 diabetes and hyperlipidaemia.
• Females with Turner syndrome are born with only one X chromosome.

Aetiology Explained.

• In Turner syndrome, the genotype is 45XO or monosomy X.
• This is most commonly caused by a non-disjunction mutation during meiosis.
• Up to 50% of patients have mosaic Turner syndrome, where some cells have 45XO and some have 46XX genotypes.
• Affects many more pregnancies, but only 1% survive to term.

Short Stature

• Females reach approximately 20cm less than average female height without treatment during childhood.
• Growth rate may slow and short stature becomes very apparent during puberty when they fail to undergo normal pubertal growth spurts because of hormone insufficiency secondary to ovarian dysgenesis.

Delayed Puberty

• Girls are commonly identified when they present concerned they haven’t undergone menarche like their peers.
• Amenorrhoea and infertility are caused by primary hypogonadism due to ovarian dysgenesis.

Systemic Manifestations of Turner Syndrome

• Renal tract abnormalities: horseshoe kidney.
• Cardiac abnormalities: bicuspid aortic valve or aortic coarctation.
• Recurrent otitis media and conductive hearing loss.
• Autoimmune disease: hypothyroidism, type one diabetes mellitus, coeliac disease.

Learning Difficulties

• Most girls have good language and reading skills but may experience behavioural and social difficulties.

Clinical Examination

• On general examination, peripheral stigmata of Turner syndrome include webbed neck, cubitus valgus, broad chest with widely spaced nipples, short 4th digit, scoliosis, low set ears, low posterior hairline, high arch palate, and increased number of melanocytic naevi.
• On cardiovascular examination, findings may indicate aortic coarctation.
• Clinical features in the neonatal period include neonatal peripheral lymphedema, cystic hygroma, and stigmata of Turner syndrome.

Differential Diagnosis: Noonan Syndrome

• It is caused by an autosomal dominant mutation of the PTPN11 gene and can affect males or females.
• Other differential diagnosis considerations include other causes of primary ovarian failure, gonadotropin deficiency, and functional gonadotropin deficiency.

Bedside Investigations

• Blood pressure and growth assessment.
• Urine dip: assesses for complications of renal tract abnormalities.

Laboratory Investigations

• Karyotyping identifies the 45XO mutation.
• Blood tests screen for autoimmune complications.
• Hormone tests identify primary hypogonadism secondary to ovarian dysgenesis.
• Metabolic profile screens for type two diabetes and hypercholesterolemia.

Imaging Investigations

• Echocardiogram screens for bicuspid aortic valve and aortic coarctation.
• Renal tract ultrasound identifies structural abnormalities of the renal tract.
• Pelvic ultrasound checks for the presence of the uterus.
• DEXA scan identifies osteoporosis.

Other Investigations

• Pure tone audiometry screens for a conductive hearing loss.

Diagnosis

• Turner Syndrome is diagnosed via karyotyping.

Management: Hormone Replacement Therapy

• Oestrogen replacement therapy is started at age 11 to trigger breast development, maintain uterus health, and maintain bone mineral density.
• Progesterone replacement therapy is started after oestrogen replacement therapy to trigger menarche and maintain a normal menstrual cycle.
• Growth hormone is given as a daily injection from age 5-16 to help trigger growth.

Multidisciplinary Management

• A multidisciplinary management approach is required.

Complications

• Complications include autoimmune diseases, recurrent otitis media and glue ear, increased risk of urinary tract infection, osteoporosis secondary to low oestrogen, hypertension secondary to renal and cardiac abnormalities, and higher rates of type two diabetes mellitus and hyperlipidaemia.