A genetic follow up study in Turner syndrome

Turner syndrome (TS) is characterized by the partial or complete absence of the
second X chromosome. Forty to sixty percent of TS patients have the karyotype
45,X. The other patients show either a mosaicism consisting of at least one
cell line containing 45,X, or a structural aberration of the second X
chromosome (i.e. Xp or Xq deletion, isochromosome Xq, or ring X). The majority
of patients with mosaicism shows considerable tissue-specific differences in
levels of X-aneuploidy. In approximately 5% of TS women, cytogenetic
examination shows cells containing Y chromosomal material. Detecting Y
chromosomal material is important since this is a risk factor for the
development of gonadoblastoma. Around 60 to 80 percent of patients with 45,X
karyotype have maternally derived X chromosomes. Specific cognitive skills,
visceral adiposity and statural growth have been linked to the parental origin
of the single normal X chromosome in TS. Research on the effect of having a
maternally or paternally derived X chromosome on growth and other clinical
features can improve quality of treatment of girls and women with Turner
syndrome.
The prevalence of heterozygosity of a deletion of exon 3 in the GH receptor
gene (a polymorphism; d3-GHR) in humans is approximately 25 to 32%, while
homozygosity is found in 9 to 14%. It has been reported that the presence of a
d3-GHR resulted in an increased responsiveness to GH therapy in short children
without GH deficiency. Genotyping d3-GHR might provide a tool for a more
precise understanding of the growth promoting effects of GH therapy in the
individual TS patient.

The main objective is to assess the frequency of hidden mosaicism, including Y
material, in TS patients and examine the effect on: response to different GH
doses and GH injection frequency regimens, aortic diameter and distensibility,
congenital cardiac malformations, lipid profile, dysmorphic features and the
frequency of gonadoblastoma in individuals with Y material. Other objectives
are to assess the effect of paternal or maternal origin of the X chromosome and
the effect of d3-GHR on the effect of GH dose and injection frequency, on final
height and final height gain.

Observational study.

This non-therapeutic, observational study does not entail any known risks. The
burden imposed by the study is mainly the time investment needed for coming to
the hospital, the questionnaires, the clinical examination, the making of the
photographs and the collecting of the different tissues. The study therefore
meets the requirement of negligible risk and minimal burden. A benefit from
taking part in the study is a free and detailed genetic analysis. This may be
very valuable for the patients and parents or legal guardians of patients with
TS.