Turner syndrome is a pattern of malformation characterized by short stature, ovarian hypofunction, loose nuchal skin, and cubitus valgus, as described by Turner in 1938. An associated 45,X chromosome constitution was recognized by Ford et al in 1959. Karyotypes discovered in subjects with phenotypic characteristics of Turner syndrome are described in Table E1.

One case in every 2500 to 5000 live female births

• Turner phenotype is recognizable at any point on the developmental spectrum.
• In spontaneous abortions, it is the most common sex chromosome abnormality detected (45,X chromosome constitution) and accounts for 20% of such cases.
• In fetuses, it is suspected when ultrasonographic manifestations such as thickening of the nuchal folds, frank nuchal cystic hygromas, or mild shortness of the femur at midtrimester are identified.
• In infants (Fig. E1):
  1. At birth may display loose nuchal skin (pterygium colli) and edema on the dorsa of hands and feet
  2. Canthal folds reflecting midface hypoplasia and redundant skin in the periorbital region
  3. Nipples appearing widely spaced (interthelial distance greater than one fourth the chest circumference)
  4. Heart and cardiovascular system: Murmur of aortic stenosis or bicuspid aortic valve or diminished femoral pulses suggestive of aortic coarctation
  5. Renal ultrasonography: Renal ectopia such as pelvic kidney or horseshoe kidneys
• In older children:
  1. Slow linear growth.
  2. Short stature: May be improved with growth hormone therapy. Combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement.
  3. Delayed or absent menses: Secondary sex characteristics possibly normalized with estrogen replacement therapy.
  4. Intelligence is often normal, but delays in spatial perception or visual-motor integration are commonly observed; frank developmental impairment is rare.

• Abnormal phenotype caused by absence of the second sex chromosome, whether X or Y
• 45,X chromosome constitution in approximately 50% of affected individuals
• Other chromosome aberrations (40% of cases): Isochromosome Xq (46,X,i[Xq]) or mosaicism (XX/X)
• With deletions involving the short (or “p”) arm of the X chromosome: Short stature but little ovarian hypofunction
• Deletions involving Xq13-q27: Ovarian failure
• Usually a deficiency of paternal contribution of sex chromosome, reflecting paternal nondisjunction

• Noonan syndrome (PTPN11 mutation), an autosomally dominant inherited disorder also characterized by loose nuchal skin, midface hypoplasia, canthal folds, and stenotic cardiac valvular defects and affecting males and females equally; also have normal chromosome constitutions
• Other conditions in the differential diagnosis of loose skin, whether or not associated with edema:
  1. Fetal hydantoin syndrome (loose nuchal skin, midface hypoplasia, distal digital hypoplasia)
  2. Disorders of chromosome constitution (trisomy 21, tetrasomy 12p mosaicism)
  3. Congenital lymphedema (Milroy edema)

• Giemsa banded karyotype to confirm clinical diagnosis
• Cardiologic consultation for evaluation for cardiac valvular abnormalities or aortic coarctation
• Renal ultrasonography after diagnosis is established
• Endocrine evaluations in older patients with short stature or amenorrhea
• Psychometrics to document known or suspected learning disabilities

• As noted, routine Giemsa banded karyotype on peripheral lymphocytes is the gold standard to confirm the clinical impression in all suspected cases of Turner syndrome
• Important to exclude the presence of Y chromosome in mosaics
• Recognition of associated medical problems, such as hypergonadotropic hypogonadism or autoimmune thyroiditis, prompting periodic evaluation of these potential areas

• Echocardiography
• Renal ultrasonography
• Abdominal ultrasonography for evaluation of ovarian and uterine size and morphology
• MRI of brain (especially in cases with known or suspected neurologic impairment)
• Radiography (for evaluation of carpal/metacarpal abnormalities, radioulnar synostosis)
• Bone age (for evaluation of short stature)

General medical care guided by normal medical standards with special attention paid to identifying such age-related problems as developmental delays, learning disabilities, slow growth, or amenorrhea

Specific treatment geared to the specific medical problem (e.g., cardiac or renal dysfunction)

• Estrogen-replacement therapy in early adolescents
• Some benefit from recombinant human growth hormone therapy

• To geneticist: Clinical diagnosis, differential diagnosis, recurrence risk counseling, cytogenetic tests
• To endocrinologist (pediatric): Evaluation of short stature, estrogen or growth hormone replacement therapy
• To cardiologist: For cardiac valvular abnormalities or aortic coarctation

• Although newer studies are optimistic regarding outcomes, previous reports suffered from retrospective observations, case reports, and ascertainment bias, contributing to a generally poor interaction between the physician and patient.
• Affected individuals and families often benefit from the contemporary experiences and expertise of members of genetic support groups. The Turner Syndrome Society of the United States (800-365-9944; www.turnersyndrome.org" www.turnersyndrome.org) and the Alliance of Genetic Support Groups (800-336-4363 or 202-966-5557; http://geneticalliance.org) are valuable resources.
• A diagnosis of Turner syndrome should be considered in all girls with short stature or primary amenorrhea.
• Almost all women with Turner syndrome are infertile, although some conceive with assisted reproduction.

Turner Syndrome (Patient Information)