(Monosomy X; Gonadal Dysgenesis)
Turner syndrome occurs in about 1/2500 live female births worldwide. However, 99% of 45,X conceptions abort spontaneously.
About 50% of affected girls have a 45,X karyotype; about 80% have lost the paternal X. Most of the other 50% have mosaicism (eg, 45,X/46,XX or 45,X/47,XXX). Among mosaic girls, phenotype may vary from that of typical Turner syndrome to normal. Occasionally, affected girls have one normal X and one X that has formed a ring chromosome. Some affected girls have one normal X and one long-arm isochromosome formed by the loss of short arms and development of a chromosome consisting of two long arms of the X chromosome. These girls tend to have many of the phenotypic features of Turner syndrome; thus, deletion of the X chromosome’s short arm seems to play an important role in producing the typical phenotype.
Common cardiac anomalies include coarctation of the aorta and bicuspid aortic valve. Hypertension frequently occurs with aging, even without coarctation. Renal anomalies and hemangiomas are frequent. Occasionally, telangiectasia occurs in the gastrointestinal (GI) tract, with resultant GI bleeding or protein loss. Hearing loss occurs; strabismus and hyperopia (farsightedness) are common and increase the risk of amblyopia. Thyroiditis, diabetes mellitus, and celiac disease are more common than among the general population.
Infants are at a higher risk of developmental dysplasia of the hip. Of adolescents, 10% have scoliosis. Osteoporosis and fractures are fairly common among women with Turner syndrome. Gonadal dysgenesis (ovaries replaced by bilateral streaks of fibrous stroma and devoid of developing ova) occurs in 90% of females. Between 15% and 40% of adolescents with Turner syndrome undergo spontaneous puberty, but only 2 to 10% undergo spontaneous menarche.
Intellectual disability is rare, but many girls have nonverbal learning disability, attention-deficit/hyperactivity disorder, or both and thus score poorly on performance tests and in mathematics, even though they score average or above in the verbal components of intelligence tests.
Many neonates are very mildly affected; however, some present with marked dorsal lymphedema of the hands and feet and with lymphedema or loose folds of skin over the back of the neck. Other frequent anomalies include a webbed neck and a broad chest with widely spaced and inverted nipples. Affected girls often are short in stature compared with family members.
Less common findings include a low hairline on the back of the neck, ptosis, multiple pigmented nevi, short 4th metacarpals and metatarsals, prominent finger pads with whorls in the dermatoglyphics on the ends of the fingers, and hypoplasia of the nails. Increased cubitus valgus (carrying angle) at the elbow occurs.
Symptoms of cardiac anomalies depend on severity. Coarctation of the aorta can cause high blood pressure in the upper extremities, diminished femoral pulses, and low or absent blood pressure in the lower extremities.
Gonadal dysgenesis results in the inability to undergo puberty, develop breast tissue, or begin menses. Other medical problems that are associated with Turner syndrome develop with aging and may not be evident without screening.
In neonates, the diagnosis of Turner syndrome may be suspected based on the presence of lymphedema or a webbed neck. In the absence of these findings, some children are diagnosed later, based on short stature, lack of pubertal development, and amenorrhea.
Diagnosis is confirmed by cytogenetic analysis (karyotyping, FISH analysis, and/or chromosomal microarray analysis). (See also diagnosis of chromosomal anomalies and also Next-generation sequencing technologies.)
Echocardiography or MRI is indicated to detect cardiac anomalies and for ongoing surveillance.
Cytogenetic analysis and Y-specific probe studies are done for all people with gonadal dysgenesis to rule out mosaicism with a Y-bearing cell line (eg, 45,X/46,XY). These people are usually phenotypic females who may have variable features of Turner syndrome. They are at an increased risk of gonadal tumors, especially gonadoblastomas, some of which may become malignant. Because of this potential for cancer, prophylactic gonad removal, although controversial, is often recommended.
Certain routine evaluations help identify problems that may be associated with Turner syndrome (1):
Cardiology evaluation with echocardiography and ECG at time of diagnosis, and ongoing evaluation to monitor for conduction abnormalities and aortic dilation
Renal ultrasonography at time of diagnosis, annual urinalysis, blood urea nitrogen, and creatinine for patients with renal system anomalies
Hearing evaluation by an audiologist and audiogram every 3 to 5 years
Ophthalmology evaluation at age 12 to 18 months or at time of diagnosis; annual evaluation thereafter
Thyroid function tests at diagnosis and annually thereafter
Celiac screen (eg, endomysial antibody levels)
Annual screening for glucose intolerance starting at age 10 years
There is no specific treatment for the underlying genetic condition, and management is based on an individual's findings.
Coarctation of the aorta is usually repaired surgically. Other cardiac anomalies are monitored and repaired as needed.
Lymphedema can usually be controlled with support hosiery and other techniques such as massage.
Treatment with growth hormone can stimulate growth. Estrogen replacement is usually needed to initiate puberty and is typically given at age 12 to 13 years. Thereafter, birth control pills with a progestin are given to maintain secondary sexual characteristics. Growth hormone can be given with estrogen replacement until epiphyses are fused, at which time growth hormone is stopped. Continuation of estrogen replacement helps establish optimal bone density and skeletal development.
Girls are missing all or part of one of their two X chromosomes in some or all cells tested.
Manifestations vary, but short stature, webbed neck, broad chest, gonadal dysgenesis, and cardiac anomalies (commonly coarctation of the aorta and bicuspid aortic valve) are common; intellectual disability is rare.
Risk of gonadal cancer is increased; it is often recommended to remove the gonads prophylactically, although this is controversial.
Do routine age-specific screening to detect associated medical conditions (eg, cardiac and renal anomalies).
Treat with hormones to initiate puberty and maintain secondary sexual characteristics.
Treat specific manifestations, and provide social and educational support and genetic counseling.