Turner Syndrome

Author: Stefania Corvisieri
Date: 30/03/2009



written by Palmese Eleonora and Corvisieri Stefania

The Turner Syndrome is a chromosomal disorder affecting females in which all or part of one of the X chromosome is absent

Diseases Database: The Turner Syndrome


Occurring in 1 out of every 2500 girls.


- Wide rib cage/shield chest
- Late puberty/hypogonadism
- Abnormal ovaries (the ovaries are usually replaced by streaks of connective tissue with no germinal elements)
- Coarctation of the aorta
- Short stature.
- Webbed neck

For additional signs: Wikipedia


Turner syndrome may be diagnosed by amniocentesis during pregnancy. Sometimes, fetuses with Turner syndrome are identified by abnormal ultrasound findings (i.e. heart defect, kidney abnormality, cystic hygroma). A test, called a karyotype, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.


The only monosomy compatible with live birth is the 45,X condition, which causes Turner syndrome. The 45,X phenotype is mild, presumably because the second copy of many X chromosomal genes is normally inactivated. Several other structural abnormalities of the X chromosome such as deletions, isochromosome X, or ring chromosomes can cause Turner syndrome. Mosaicism, including 45,X/45,XX, 45X/45,XXX, 45,X/45,XY, and others, also occurs and contributes to the phenotypic spectrum in Turner syndrome.

Genes implicated in phenotype are:

- Gene SHOX (short stature homeobox) belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients. Gene SHOX OMIM gene SHOX

- Genes POF-1(Xq26) and POF-2(Xq13-21), implicated in function of ovaries. OMIM Premature ovarian failure

- Gene SRY (on the Y chromosome). A systematic search for hidden Y-chromosome mosaicism, especially SRY (testis determining factor), in Turner syndrome patients is justified by the possibility of preventing gonadal lesions, in fact the presence of Y-chromosome increases the risk of developing gonadoblastoma. OMIM SRY

- X-linked FOXP3 gene is associated with the autoimmune susceptibility in Turner Syndrome. OMIM FOXP3


In particular:

  • an increased risk of celiac disease
  • Hashimoto's thyroiditis (one-third of all women with Turner syndrome have a thyroid disorder)
  • a moderately increased risk of developing type 1 diabetes in childhood.

The role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients
FOX (Forkhead box) are a family of proteins that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development. The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix due to the butterfly-like appearance of the loops in the protein structure of the domain. Forkhead genes are a subgroup of the helix-turn-helix class of proteins.
FOXP3 has been mapped to chromosome Xp11.23 and encodes a DNA-binding protein. This protein has a DNA binding domain (forkhead/winged-helix) in the carboxyl-terminal , a C2H2 zink finger and a leucine zipper domain in the central portion and a N-terminal region rich of Prolina (this region is involved in inhibition of transcription).
FOXP3 is important in the development of regulatory T cells, and complete loss of FOXP3 expression has been shown to result in severe autoimmunity.
Naturally arising FOXP3-expressing CD25+ CD4+ regulatory T-cells in immunological tolerance to self and non self
Naturally occurring CD25+CD4+ regulatory T cells are engaged in the maintenance of immunological self-tolerance and down-regulation of various immune responses. Recent studies with mice showed that Foxp3, which encodes the transcription factor Scurfin, is a master regulatory gene for the development and function of CD25+CD4+ regulatory T cells. TCR stimulation of CD25––CD4+ naive T cells (non regolatori) failed to elicit FOXP3 expression at the gene or protein level. Ex vivo retroviral gene transfer of FOXP3, on the other hand, converted peripheral CD25–CD4+ naive T cells into a regulatory T cell phenotype similar to CD25+CD4+ regulatory T cells. For example, FOXP3-transduced T cells exhibited impaired proliferation and production of cytokines including IL-2 and IL-10 upon TCR stimulation, up-regulated the expression of regulatory T cell-associated molecules such as CD25 and CTL-associated antigen-4 and suppressed in vitro proliferation of other T cells in a cell–cell contact-dependent manner. Thus, human FOXP3 is a crucial regulatory gene for the development and function of CD25+CD4+ regulatory T cells, and can be used as their reliable marker. Furthermore, regulatory T cells de novo produced from normal naive T cells by FOXP3 transduction can be instrumental for treatment of autoimmune/inflammatory diseases and negative control of various immune responses.


Management should include growth hormone therapy and estroprogestinici replacement therapy at doses sufficient to promote growth without inducing the early welding of cartilage epifisarie, to keep the secondary sexual characteristics, to have regular menstruation and prevent osteoporosis.

GH treatment and Turner syndrome

The d3-Growth Hormone Receptor Polymorphism is Associated with Increased Responsiveness to GH in Turner Syndrome

GH is capable of stimulating short-term growth and augmenting adult height in girls with TS. With early diagnosis and initiation of treatment (at 6-7 years hold), an adult height of more than 150 cm is a reasonable goal for most girls with TS.
A protein polymorphism of the GH receptor (OMIM GHR) based on the genomic deletion of exon 3 (d3-GHR) has recently been linked to the magnitude of growth response to high-dose recombinant human GH (rhGH) therapy. So we can hypothesize a insensitivity to growth hormone (as in Laron Syndrome )

2009-04-14T13:11:17 - Gianpiero Pescarmona

Expression of FOXP3, a potent gene-specific transcriptional repressor , in regulatory T cells is required to suppress autoreactive and alloreactive effector T cell function. Recent studies have shown that FOXP3 is an acetylated protein in a large nuclear complex and FOXP3 actively represses transcription by recruiting enzymatic corepressors, including histone modification enzymes. The mechanism by which extracellular stimuli regulate the FOXP3 complex ensemble is currently unknown. Although TGF-beta is known to induce murine FOXP3 Treg cells, TGF-beta in combination with IL-6 attenuates the induction of FOXP3 functional activities. Here we show that TCR stimuli and TGF-beta signals modulate the disposition of FOXP3 into different subnuclear compartments, leading to enhanced chromatin binding in human CD4CD25 regulatory T cells. TGF-beta treatment increases the level of acetylated FOXP3 on chromatin and site-specific recruitment of FOXP3 on the human IL-2 promoter. However, the proinflammatory cytokine IL-6 down-regulates FOXP3 binding to chromatin in the presence of TGF-beta. Moreover, histone deacetylation inhibitor (HDACi) treatment abrogates the down-regulating effects of IL-6 and TGF-beta. These studies indicate that HDACi can enhance regulatory T cell function via promoting FOXP3 binding to chromatin even in a proinflammatory cellular microenvironment. Collectively, our data provide a framework of how different signals affect intranuclear redistribution, posttranslational modifications, and chromatin binding patterns of FOXP3.

TGF-beta and IL-6 signals modulate chromatin binding and promoter occupancy by acetylated FOXP3. 2008

FOXP3 has

  • low tirosina, glutamato (Glu/Gln ca 1)
  • high proline, fenilanina, metionina

Low oxygen?

Expected effects

  • Low proliferation rate
  • High collagen synthesis

If I have less HDAC activity, less proliferation, more NADPH more FOXP3

Using histone deacetylase inhibitors to enhance Foxp3 regulatory T-cell function and induce allograft tolerance. 2009

GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. 2007

Sindrome di Turner, oxandrolone solo a basse dosi
È da sconsigliare l'impiego convenzionale di oxandrolone in ragazze affette dalla sindrome di Turner e sottoposte al trattamento con l'ormone della crescita. Queste le conclusioni di uno studio pubblicato su Journal of Clinical Endocrinology & Metabolism che ha evidenziato un rapporto rischi-benefici svantaggioso quando lo steroide anabolizzante viene utilizzato al dosaggio standard, corrispondente a 0,06 mg/kg al giorno. L'indagine randomizzata e in doppio cieco è stata condotta presso 10 centri olandesi. 133 ragazze con sindrome di Turner, suddivise in tre gruppi in base all'età: gruppo 1 (2-8 anni); gruppo 2 (8-12 anni) e gruppo 3 (12-16 anni), sono state randomizzate a ricevere, in aggiunta all'ormone della crescita (1,33 mg/m2/giorno), placebo; oxandrolone a basse dosi (0,03 mg/kg/giorno) oppure al dosaggio standard (0,06 mg/kg/giorno) a partire dagli otto anni d'età ed estrogeni dai 12 anni in poi. In breve, oxalondrone è risultato in grado di determinare un aumento dell'altezza in età adulta, rispetto al placebo, a basse dosi (valore medio = 9,5 ± 4,7 vs 7,2 ± 4,0 cm; p = 0,02) e non a quelle convenzionali (8,3 ± 4,7 vs 7,2 ± 4,0 cm; p = 0,3). Un numero più elevato di ragazze, nel gruppo trattato con dosi elevate dello steroide, hanno mostrato segni di virilismo rispetto a quelle sottoposte a placebo.

J Clin Endocrinol Metab. 2010 Mar;95(3):1151-60. Epub 2010 Jan 8.

AddThis Social Bookmark Button