Turner syndrome

Published on 02/04/2015 by admin

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Last modified 22/04/2025

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233 Turner syndrome

Instruction

Look at this patient.

Salient features

Examination

Fig. 233.1 A 15-year-old girl exhibiting failure of sexual maturation, short stature, cubitus valgus and a goitre. There is no webbing of the neck.

(With permission from Kliegman et al. 2007.)

Proceed as follows:

• Tell the examiner that you would like to:

• examine genitalia for infantilism

• measure serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (these will be high, confirming primary hypogonadism)

• check thyroid-stimulating hormone (hypothyroidism occurs in 15 to 30%)

• order a renal ultrasound (kidney malformations, including horseshoe kidney and duplication of the collecting system, are found in up to 40%)

• echocardiogram: as physical examination may be inadequate to detect a bicuspid aortic valve

• request for a formal assessment of learning disability (~70% have learning disabilities affecting non-verbal perceptual motor and visuospatial skills).

Diagnosis

This patient has Turner syndrome (lesion), which is caused by the absence of one of the X chromosomes (aetiology). She has amenorrhoea and skeletal abnormalities (functional status).

Questions

What constitutes a web?

Either a fan-like fold of skin extending from the shoulder to the neck or an abnormal splaying out of the trapezius.

Advanced-level questions

Which other cardiovascular lesions are associated with webbing of the neck?

Noonan syndrome or Ullrich syndrome with pulmonary stenosis.

What are the facial features of Turner syndrome?

Ptosis, micrognathia, low-set ears, epicanthal folds.

What are the renal abnormalities associated with Turner syndrome?

Horseshoe kidney, hydronephrosis.

Is pregnancy possible in these patients?

Only in mosaic individuals with a normal 46XX cell line; in this group sufficient follicles may persist postnatally to initiate pubertal changes and, therefore, cause ovulation and consequently pregnancy.

How would you manage such patients?

The treatment is supportive and includes replacement hormone therapy on attaining puberty, primarily to prevent osteoporosis and induce sexual maturation and menses.

What is the chromosomal defect in Turner syndrome?

It is caused by the absence of one of the X chromosomes (blood karyotype showing 46,XO). Other variants of the syndrome include 46,X (with abnormal X), 45,XO/46,XX mosaics and 45,XO/46,XY mosaics. Although this is the single most common chromosomal disorder, >95% of the foetuses are aborted, which results in an incidence of ~1 in 4000 newborns. Women with a 45,X/46,XX karyotype and a preponderance of 46,XX cells may have all the findings of the disorder.

Loss of SRY on the short arm of the Y chromosome (e.g. 46,X,del(Yp)) encoding a testis-determining factor, also leads to the phenotype of Turner syndrome, even without a 45,X cell population.

Is there a correlation between karyotype and phenotype?

There are some correlations between karyotype and phenotype, but note that phenotypic predictions for a given patient that are based on karyotype may not be reliable (e.g. women with a 45,X karyotype have conceived).

Growth failure

• Loss of interstitial or terminal long-arm material of the X chromosome (Xq) can result in short stature and primary or secondary ovarian failure.

• Deletions distal to Xq21 appear to have no effect on stature.

• Loss of the short arm (Xp) results in the full phenotype.

• Very distal Xp deletions are compatible with, but do not ensure, normal ovarian function. Loss of this region usually confers short stature and the typical skeletal changes, in part as a result of haploinsufficiency of the short stature–homeobox (SHOX) gene, located in the pseudoautosomal region of Y and Xp. (SHOX is probably not the only gene that determines skeletal features.)

• Aneuploidy itself may contribute to growth failure.

• Women with mosaicism for 45,X/46,XX are marginally taller than other women with Turner syndrome.

Neurocognitive defects

• Loss of a region at Xp22.3 appears to be associated with the neurocognitive problems.

• The presence of a ring or marker chromosome confers an increased risk of mental retardation and atypical phenotypic features.

Lymphoedema

• A region on Xp11.4 has been postulated to be important for the development of lymphoedema.

• Infants with a 45,X karyotype are the most likely to have congenital lymphoedema.

Reproductive organs

• A karyotype of 45,X/46,XX or 45,X/47,XXX is most likely to be associated with spontaneous menarche and fertility.

• Girls with mosaicism for a cell population with a Y chromosome are at increased risk for gonadoblastoma (risk, 7–30%) in their streak gonads.

Hypothyroidism and inflammatory bowel disease

• The presence of an isochromosome Xq suggests an increased risk for hypothyroidism and inflammatory bowel disease.

What do you know about Lyon’s hypothesis?

In 1961, geneticist Mary Lyon outlined that only one of the X chromosomes is genetically active, the other being inactive. The inactivation of either the maternal or paternal X chromosome occurs at random among all the cells of the blastocyst around the 16th day of embryonic life, and inactivation of the same X chromosome persists in all cells derived from each precursor cell.

More recent studies, however, have shown that many genes escape X chromosome inactivation and that both X chromosomes are important for normal growth, as evidenced by severe abnormalities in Turner syndrome with a monosomy of X chromosome. It is now believed that a gene that maps to Xq13 serves as a master switch which is critical for ‘switching-off’ most of the genes on the active chromosome 13. This gene is known as X-inactive-specific transcript gene (XIST).

Henry H Turner (1892–1970), an American endocrinologist, described this condition in 1938.

Mary Lyon (b. 1925), geneticist who worked for the Medical Research Council in Oxford.

There are several support groups for patients with Turner syndrome and their families.

Turner Syndrome Society of UK is such a support group; 12 Irving Quadrant, Hardgate, Clydebank G81 6AZ, UK; telephone +44(0)1389–380385; fax +44(0)1389–380384; e-mail Turner.Syndrome@tss.org.uk; or see www.tss.org.uk/contact.html. It provides:

• free growth charts for patients with Turner syndrome

• publications at cost (e.g. Reiser PA, Underwood LE. Turner syndrome: a guide for families, 1992, Rosenfeld RG. Turner syndrome: A guide for physicians, 1992).

• videotapes of their annual conferences, available for a fee.

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