Key Points
Disease summary:
Caused by complete or partial loss of the second sex chromosome (45,X karyotype).
The great majority of 45,X gestations end in fetal demise by end of first trimester.
Approximately 1/2500 live born females have Turner syndrome (TS).
Extreme short stature may be prevented by growth hormone RX during childhood.
Secondary sexual development and normal sexual functioning are achieved with estrogen replacement treatment.
The other features if diagnosed and remedied in a timely manner need not impair longevity or quality of life.
Hereditary basis:
TS is a sporadic disorder occurring due to nondisjunction or fragmentation of sex chromosomes during gametogenesis or early embryonic development.
Differential diagnosis
Noonan syndrome—the physical phenotype may mimic TS, with short stature and residual evidence fetal lymphedema (eg, neck webbing) and congenital heart disease (CHD). The karyotype of this autosomal dominant syndrome is normal, however.
Idiopathic short stature with constitutional delay of puberty—the karyotype in these children is also normal.
Diagnostic Criteria and Clinical Characteristics
Criteria include short stature and at least one or other of the cardinal or major features listed below in a phenotypic female, confirmed with a 20-cell karyotype revealing loss of all or parts of one sex chromosome.
Cardinal features (>90% of cases) include phenotypic female, short stature most evident by age 12, ovarian failure, absent pubertal development, infertility by age 12 to 20.
Major features (∼50% of cases) include CHD, sensorineural hearing loss by age 30 to 40 and thyroid autoimmune disease begins in childhood, peaking approximately at age 50.
Minor features (≤30% of cases) include renal anomalies such as horseshoe kidney, hypertension—may begin in childhood, type 2 diabetes in adults aged 30 and up, lymphedema-neck webbing (a residual of fetal cystic hygroma; a few patients have persistent peripheral lymphedema).
Screening and Counseling
In the setting of an abnormal fetal ultrasound (cystic hygroma, hydrops, cardiovascular defects) the finding of 45,X from chorionic villous or amniocentesis carries a grave prognosis in terms of fetal survival. However, this scenario is compatible with delivery of a viable newborn. In a contrasting situation, a sex chromosome anomaly is detected during routine prenatal screening; the degree of mosaicism detected prenatally is not generally predictive of the severity of the TS phenotype. Particularly if the fetal ultrasound is normal, there may be little clinical consequence of the prenatal karyotype, and chromosomes need to be re-evaluated in the newborn. In general, prenatally diagnosed girls tend to be less affected than those diagnosed postnatally.
TS is a sporadic disorder but recurrence that has rarely been reported suggests that recurrence risk is probably increased after the first TS pregnancy and an estimate of 1.4% has been reported based on one small case series of 140 TS patients.
