Turner syndrome Prevalence, Types of chromosomal anomalies, Typical Features, Diagnosis, Monitoring, Management, Adult Management

1. Turner Syndrome
Tural Abdullayev
William Ulf Sollin

2. Prevalence
• One of the most common sex chromosome
abnormalities in females
– 1 in 2000 to 1 in 2500 live female births
– However
• Many terminate the pregnancy early after prenatal
testing
• Most gestations affected by X chromosome monosomy
(45,X) do not survive to birth
• 45,X genotype is found in at least 10 percent of
spontaneous abortions

3. Types of chromosomal anomalies
• 45,X (monosomy X)(~45%)
– 2/3 from the mother
• 45,X/46,XX or 45,X/47,XXX
– Presence and degree of mosaicism may differ among different tissues
• 45,X mosaics
– Presence and degree of mosaicism may differ among different tissues
– Isochromosome Xq (46,X,i(X)q)
• Structurally abnormal X chromosome
• Two copies of the long arm of the X chromosome connected head-to-head
– Ring chromosome X (rX)
• May form if part of the end of both the short and long arms of the X
chromosome are missing
– Xp or Xq deletion
• Deletion of a portion of the short arm of the X chromosome

4. Typical features
• short stature
• “Shield” chest with widely spaced nipples
• Short and webbed neck
• Cubitus valgus
• Madelung deformity of the forearm and wrist

5. Clinical Manifestations

6. Indication for testing
As the only clinical feature:
•Fetal cystic hygroma, or hydrops, especially when severe
•Idiopathic short stature
•Obstructive left-sided congenital heart defect*
•Unexplained delayed puberty/menarche
•Couple with infertility
•Characteristic facial features in a female
¶
At least two of the following:
•Renal anomaly (horseshoe, absence, or hypoplasia)
•Madelung deformity
•Neuropsychologic problems, and/or psychiatric issues
•Multiple typical or melanocytic nevi
•Dysplastic or hyperconvex nails
•Other congenital heart defects
Δ
•Hearing impairment <40 years of age together with short stature

7. Diagnosis
• Turner syndrome is occasionally diagnosed incidentally during
prenatal testing
• Suspected based upon characteristic clinical features.
• Diagnosis is confirmed by karyotype analysis
– If neg. first test, repeat with other tissue
– Important to permit management of comorbidities (eg. short stature)
– PCR can also be used (95% sensitivity)
– Y chromosome mosaicism — Y chromosome material (associated with
an increased risk of gonadoblastoma) is found in approximately 6 to 11
percent of patients with Turner syndrome using standard cytogenetic
techniques. Patients with virilization or marker chromosome elements
(sex chromosome material of uncertain origin) detected on the
karyotype undergoes additional testing to look for occult Y
chromosome mosaicism using techniques such as fluorescence in situ
hybridization (FISH) with different probes specific for the X and Y
chromosome.

8. Monitoring & Management
• Cardiovascular anomalies
• Hypertension
• Cognitive function and learning disabilities
– Attention deficit disorder and difficulties with visual-spatial organization,
social cognition, and nonverbal problem-solving tasks such as mathematics
• Tympanometry and audiology
• Scoliosis and kyphosis
• Cancer risk
• Other
– Renal anomalies
– Autoimmune thyroiditis
– Celiac disease
– Eyes
– Edema

9. Short Stature Management
• Growth hormone therapy
– If height of a girl with Turner syndrome falls below the 5th percentile
for age
– Two - five years of age
• Growth hormone therapy plus oxandrolone (anabolic steroid)
– If unlikely to reach the 5th percentile for the adult general female
population
• Management of ovarian failure (hypogonadism)
– Estrogen therapy
• Reflect normal puberty (11-12y)
• Low dose estradiol
– Adjunctive progestins (Cyclic)
• To avoid endometrial hyperplasia

10. Adult Monitoring
• Cardiovascular
• Estrogen thereapy monitoring
• Audiology testing
• Bone densitometry
• Routine testing
– Glucose
– Liver
– Renal
– Thyroid
– Celiac
• Aortic dissection
• Why important?
– 3x mortality risk occurring at all ages and for most major causes of
death