Turner Syndrome Pathogenesis and Clinical Findings

Turner Syndrome: Pathogenesis and clinical findings
Author: Simran Pherwani Ashar Memon, Christy Chong Reviewers: Tara Shannon Simran Sandhu, Mao Ding Danielle Nelson* * MD at time of publication
Non-disjunction in phenotypically female gametes (i.e. homologous X-chromosomes or sister chromatids fail to separate)
Partial or complete absence of second sex chromosome, leaving only one normal X-chromosome
Possible Chromosomal Profiles
Other meiotic error → deletion or misdivision of X-chromosomal material
Complete loss of one X- chromosome in all cells (45,X) (45%)
Skeletal Abnormalities
↓ Expression of SHOX gene (present on X- and Y-chromosomes)
↓ Cellular proliferation in growth plates of bones in extremities during embryonic development
Short stature
High-arched palate
Genu valgum (knock knees)
Micrognathia (smaller lower jaw)
Broad chest
Cubitus valgus (forearm angled outward)
Mosaicism (complete loss of one X-chromosome in some cells (e.g., 45,X/46,XXX, etc)) (50%)
Congenital Heart Defects (most serious)
Single copy of TIMP1 gene and presence of risk TIMP3 allele, and differential expression of KDM6A gene
Bicuspid aortic valve
Aortic coarctation
Aortic dilation (worsened by hypertension)
One X-chromosome and presence of Y-chromosomal material in some or all cells (e.g., 45,X/46,XY)
Presence of an
X- isochromosome (most commonly i(Xq))
Other structural abnormalities of X-chromsome (e.g., Ring Chromosome X, partial deletion of X, X or Y marker chromosome)
Endocrine Disorders
Turner Syndrome
The most common sex chromosomal abnormality in females (affects 1/2000-3000)
Results in deletion or non- functioning of one X chromosome
Clinical presentations vary depending on chromosome profile
Aortic dissection
Renal disease
Neurocognitive Deficits
Mechanism unknown
Deficit in social skills
Specific (non-verbal) learning disorder (otherwise normal intelligence)
↓ Executive function skills
↓ Visuospatial skills ↓ Attention
Accelerated follicular apoptosis (i.e., loss of oocytes from ovaries) → streak gonads
Ovaries are unable to respond to high gonadotropins (FSH, LH)
Hypergonadotropic hypogonadism
Premature ovarian insufficiency
↓ Expression of immune- associated genes on X- chromosome
↑ Autoimmunity
Autoimmune diseases (celiac, thyroiditis, IBD, metabolic abnormalities)
↓ Estrogen levels
Lack of breast development
↑ Liver enzymes (Additional mechanisms likely)
↓ Bone mineral density
Other Dysmorphic Features
Lymphedema Webbed (buildup of lymph neck
Primary amenorrhea
Sign/Symptom/Lab Finding
Published November 25, 2023 on www.thecalgaryguide.com