🧬 Turner Syndrome

1. Definition

Turner syndrome is a chromosomal disorder affecting females, caused by complete or partial absence of one X chromosome (45,X or mosaicism).
It leads to short stature, gonadal dysgenesis, and various congenital anomalies affecting multiple systems.

2. Causes

Complete monosomy X (45,X) – most common
Mosaicism (e.g., 45,X/46,XX or 45,X/46,XY)
Structural abnormalities of X chromosome (e.g., deletions, isochromosome)

3. Risk Factors

Usually sporadic (not inherited)
No known modifiable maternal risk factors
Advanced paternal age (theoretical risk, not proven)

4. Types

Type	Description
Monosomy X (45,X)	Classic Turner, most severe phenotype
Mosaic Turner (45,X/46,XX)	Milder phenotype; may undergo puberty
Structural X defects	Ring X, isochromosome Xq

5. Pathogenesis

Loss of part or all of the second X chromosome disrupts:
- Growth regulation (short stature due to SHOX gene haploinsufficiency)
- Ovarian development (streak gonads, infertility)
- Lymphatic system development (leads to lymphedema, webbed neck)
Incomplete sexual maturation and multisystem involvement

6. Clinical Presentation

Symptoms

Short stature
Delayed or absent puberty
Infertility
Learning difficulties (especially spatial reasoning)

Signs

Lymphedema in neonates (hands, feet)
Webbed neck, low posterior hairline
Broad chest with widely spaced nipples
Cubitus valgus
High-arched palate
Cardiac murmur (due to congenital heart defects)

Physical Examination Findings

Height below 3rd percentile
Tanner stage delay
Signs of coarctation (weak femoral pulses)
Scoliosis (adolescents)

7. Organ & System Complications

System	Complications
Growth	Short stature
Gonadal	Streak ovaries, delayed puberty, infertility
Cardiac	Bicuspid aortic valve, coarctation of aorta, aortic dissection
Renal	Horseshoe kidney, duplicated collecting system
Endocrine	Hypothyroidism (autoimmune), glucose intolerance
Hearing	Recurrent otitis media, conductive hearing loss
Skeletal	Scoliosis, osteoporosis
Neurocognitive	Normal IQ but difficulty with math/spatial tasks
Psychosocial	Low self-esteem, social challenges

8. Diagnostic Investigations

Test	Purpose
Karyotype analysis	Confirm diagnosis (45,X or mosaic patterns)
FISH/array CGH	Detect low-level mosaicism or structural changes
Hormonal profile	Low estrogen, high FSH/LH (hypergonadotropic hypogonadism)
Echocardiogram	Evaluate for congenital heart disease
Renal ultrasound	Identify structural anomalies

9. Other Relevant Investigations

Test	Purpose
Thyroid function tests	Detect autoimmune hypothyroidism
Audiology evaluation	Screen for hearing loss
Bone age X-ray	Assess growth delay
Liver enzymes, lipids	Monitor metabolic risk factors
DEXA scan	Bone health, especially if estrogen deficient

10. Treatment

Curative/Definitive

None (genetic condition)

Empirical

Growth hormone (GH) therapy to optimize height (start in early childhood)

Supportive

Estrogen replacement at puberty (low dose, gradually increased)
Progesterone added to induce menses
Fertility counseling (egg donation, assisted reproduction if desired)
Regular monitoring of heart, kidneys, thyroid, hearing

Palliative

Psychosocial support, mental health counseling
Bone health maintenance (calcium, vitamin D)

11. Long-Term Medications Side Effects

Medication	Side Effects	Monitoring Tests	Expected Findings
Growth hormone therapy	Pseudotumor cerebri, scoliosis, glucose intolerance	IGF-1 levels, growth velocity, glucose	Normal IGF-1, improved height
Estrogen	Breast tenderness, mood changes, clot risk	LFTs, lipid profile	Stable liver/lipid function
Thyroxine	Tachycardia, tremor (if over-replaced)	TSH, Free T4	Normal TSH & T4

12. Surveillance for the Disease

Domain	Frequency	What to Monitor
Growth	Every 3–6 months	Height, weight, growth velocity
Puberty	Annually from age 10	Tanner staging, signs of spontaneous puberty
Cardiac	At diagnosis, then every 3–5 years	Echo, MRI for aorta, ECG
Renal	Once at diagnosis	Renal ultrasound
Thyroid	Annually	TSH, Free T4
Hearing	Annually	Audiology assessment
Bone health	From adolescence, then every 2–5 years	DEXA scan
Psychosocial	As needed	School progress, self-esteem, mental health

13. Malaysia Support Group for Parents

Support Group	Description	Contact/Link
Turner Syndrome Support Group Malaysia	Parent-led group for sharing resources and support	Facebook: Search “Turner Syndrome Malaysia”
Malaysia Rare Disorders Society (MRDS)	Advocacy, awareness, and patient support	facebook.com/MRDSMalaysia
Hospital-Based Clinics	Genetic counseling, endocrine & cardiac follow-up	Available at HKL, HUSM, UMMC, etc.