What are the characteristic clinical features of Turner syndrome?

Turner Syndrome: Characteristic Clinical Features

Turner syndrome is defined by complete or partial absence of one X chromosome (most commonly 45,X karyotype) in phenotypic females, with short stature and ovarian failure being the most prevalent findings, accompanied by significant cardiovascular abnormalities and increased mortality risk. 1

Genetic Definition and Epidemiology

• Turner syndrome results from complete or partial loss of the second X chromosome in phenotypic females, affecting approximately 1 in 2,500 liveborn girls 2, 3
• The most common karyotype is 45,X (39.2% of cases), followed by mosaicism patterns including 45,X/46,XX (19.5%), mosaicism with X chromosome structural variants (25.8%), and X chromosome structural variants alone (11.0%) 4
• Approximately 4.4% of cases have Y chromosome material present 4

Cardinal Clinical Features

Growth and Stature

• Short stature is nearly universal in Turner syndrome, present in almost all patients aged ≥2 years regardless of karyotype 5
• Mean height standard deviation score (HtSDS) at diagnosis is -3.1±1.2 4
• Short stature often goes unrecognized until late childhood, with median age at diagnosis being 9.7 years (range 6.4-12.2 years) 4

Gonadal and Reproductive Features

• Ovarian failure is one of the two most prevalent findings alongside short stature 1
• Among patients aged ≥8 years, only 28.0% show spontaneous sexual development, with mean bone age of 11.0±1.7 years 4
• Spontaneous menarche occurs in only 2.1% of cases (10 out of 471 patients aged ≥8 years), with just 2 cases achieving regular menstrual cycles 4

Cardiovascular Abnormalities

• Approximately 50% of patients have cardiovascular defects, which are critical for morbidity and mortality 2
• Bicuspid aortic valve occurs in 10-25% of patients (reported as 15-30% in some series) 1, 2
• Aortic coarctation is present in approximately 7-18% of patients 1, 2
• Ascending aortic dilation occurs in 33% of patients when defined as ascending-to-descending aortic diameter ratio >1.5 1, 2
• Congenital cardiovascular anomalies were documented in 19.4% of cases in a large Chinese cohort 4

Aortic Dissection Risk

• Women with Turner syndrome have significantly increased cardiovascular mortality, particularly from aortic dissection 1
• The population-based aortic dissection incidence is 36:100,000 Turner syndrome years (1.4% among individuals with Turner syndrome) compared with 6:100,000 in the general population 1
• Average age of aortic dissection is 31 years, with less than half of patients surviving the event 1
• 85% of dissections occur in the ascending aorta and 15% in the descending aorta 2
• Risk factors for dissection include aortic dilation, bicuspid aortic valve, aortic coarctation, and systemic hypertension 1, 2

Physical Dysmorphic Features

The following physical stigmata occur with varying frequency 4, 5:

• Cubitus valgus deformity: 85.3-94.1% of patients 5
• Nail dysplasia: 85.3-94.1% of patients 5
• Short 4th/5th metacarpals or metatarsals: 85.3-94.1% of patients 5
• Neck webbing: 17.2% 4
• Low posterior hairline: 17.0% 4
• Shield chest: 14.0% 4
• High arched palate: 11.6% 4
• Short fourth metacarpal: 3.9% 4
• Spinal abnormalities: 3.5% 4
• Lymphedema (particularly in infancy with 45,X karyotype) 6, 5

Renal and Urogenital Abnormalities

• Congenital urogenital anomalies occur in 12.0% of patients 4

Metabolic and Endocrine Features

• Dysfunction of the hypothalamic-pituitary-IGF1 axis is common: 75.9% have low IGF1 levels, with 38.2% having IGF1 SDS ≤-2 4
• Among patients undergoing growth hormone stimulation testing, 63.7% had GH peak values <10 μg/L 4
• Impaired glucose tolerance and diabetes mellitus can develop: among 23 cases undergoing OGTT, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance 4
• Fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly were found in 7.2% of cases on abdominal ultrasound 4

Hypertension

• Arterial hypertension is recorded in 13.2% of adult patients, with median age at diagnosis of 27 years 7
• The majority (75%) is classified as primary hypertension 7
• Higher body mass index is significantly associated with occurrence of hypertension 7
• Among patients with aortic disease, 50% had systolic BP ≥130 mmHg and 66.6% had diastolic BP ≥80 mmHg 7

Neurocognitive and Psychosocial Features

• Increased likelihood of difficulties with visual-spatial reasoning, executive functioning, attention, and mathematics skills 8
• Deficits in social skills and increased prevalence of anxiety are emerging areas of concern 8

Genotype-Phenotype Correlations

Classic 45,X Karyotype

• Patients with 45,X typically present earlier (median age 1 month) with predominantly lymphedema and webbed neck 5
• More severe phenotypic expression compared to mosaic forms 5

Mosaic and Structural Variants

• Patients with chromosome mosaicism or structural X abnormalities present later (median age 11 years) with a broader clinical spectrum 5
• Short stature is the most common presenting feature in this group 5
• Phenotype severity in structural variants correlates with the complexity of the X chromosome structural abnormality 9

Critical Clinical Pitfalls

• Aortic dissection can occur at relatively small absolute aortic diameters due to patients' short stature, making body size indexing (ASI calculation) essential for risk assessment 2, 3
• Non-classic Turner syndrome has subtle clinical features that may be difficult to discern, leading to delayed diagnosis 5
• Short stature, despite being universal, is frequently unrecognized until late childhood 5
• Hypertension is common and occurs at a young age, with suboptimal blood pressure control noted even in high-risk patients 7