(See also Overview of Chromosomal Anomalies Overview of Chromosomal Anomalies Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more and see Overview of Sex Chromosome Anomalies Overview of Sex Chromosome Anomalies Sex chromosome anomalies may involve aneuploidy, partial deletions or duplications of sex chromosomes, or mosaicism. (See also Overview of Chromosomal Anomalies.) Sex chromosome anomalies are... read more .)
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.
Pathophysiology of Turner Syndrome
Common cardiac anomalies include coarctation of the aorta Coarctation of the Aorta Coarctation of the aorta is a localized narrowing of the aortic lumen that results in upper-extremity hypertension, left ventricular hypertrophy, and malperfusion of the abdominal organs and... read more 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 may occur; strabismus Strabismus Strabismus is misalignment of the eyes, which causes deviation from the parallelism of normal gaze. Diagnosis is clinical, including observation of the corneal light reflex and use of a cover... read more and hyperopia (farsightedness) are common and increase the risk of amblyopia Amblyopia Amblyopia is functional reduction in visual acuity of an eye caused by disuse during visual development. Severe loss of vision can occur in the affected eye if amblyopia is not detected and... read more . 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 Developmental Dysplasia of the Hip (DDH) Developmental dysplasia of the hip (formerly congenital dislocation of the hip) is abnormal development of the hip joint. (See also Introduction to Congenital Craniofacial and Musculoskeletal... read more . 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 Attention-Deficit/Hyperactivity Disorder (ADD, ADHD) Attention-deficit/hyperactivity disorder (ADHD) is a syndrome of inattention, hyperactivity, and impulsivity. The 3 types of ADHD are predominantly inattentive, predominantly hyperactive/impulsive... read more , 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.
Symptoms and Signs of Turner Syndrome
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.
Diagnosis of Turner Syndrome
Cytogenetic testing by karyotyping, fluorescent in situ hybridization (FISH) analysis, and/or chromosomal microarray analysis
Testing for associated conditions
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 Diagnosis Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes... read more .)
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.
Concomitant medical conditions
Certain routine evaluations help identify problems that may be associated with Turner syndrome (1 Diagnosis reference In Turner syndrome, girls are born with one of their two X chromosomes partly or completely missing. Diagnosis is based on clinical findings and is confirmed by cytogenetic analysis. Treatment... read more ):
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
Evaluation for scoliosis Diagnosis Idiopathic scoliosis is lateral curvature of the spine. Diagnosis is clinical and includes spinal x-rays. Treatment depends on the severity of the curvature. Idiopathic scoliosis is the most... read more /kyphosis Diagnosis Scheuermann disease is an osteochondrosis that causes localized changes in vertebral bodies, leading to backache and kyphosis. Diagnosis is with spinal x-rays. Treatment usually involves only... read more annually during childhood and adolescence
Ophthalmology evaluation at age 12 to 18 months or at time of diagnosis; annual evaluation thereafter
Thyroid function tests at diagnosis and annually thereafter
Annual screening for glucose intolerance starting at age 10 years
Treatment of Turner Syndrome
Management of comorbid conditions
Possible surgical repair of cardiac abnormalities
Sometimes growth hormone and estrogen
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.
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