2011 Group Project 1

Note - This page is an undergraduate science embryology student group project 2011.

Turner Syndrome

Introduction

Turner syndrome (or Ullrich-Turner syndrome) is one of the most common chromosomal disorders, caused by complete or partial X monosomy in some or all cells. Approximately 1 in 2000 female live births, however the morbidity rate of spontaneous abortions is 10% and only about 1% of fetuses survive to term.

During normal fetal development, ovaries contain as many as 7 million oocytes. The oocytes gradually reduced to 400,000 during menarche and during menopause fewer than 10,000 remains. However, in Turner syndrome, the ovaries develop normally during embryogenesis but the absence of the second X chromosome leads to an accelerated loss of oocytes, which is complete by age 2 years. In this case genetically menopause occurs before menarche and the ovaries are reduced to atrophic fibrous strands, devoid of ova and follicles (streak ovaries). What is also affected is the development of somatic (nongonadal) tissues that reside on the missing/abnormal X chromosome. For example short stature is caused by a deletion of the Xp chromosome and the deletion of Xq causes gonadal dysfunction.

The most frequent clinical feature is short stature and gonadal dysgenesis. Other features may include coarctation of the aorta, renal anomalies, neck webbing, and lymphoedema. The affected organ systems and tissues may are effected to a lesser or greater extent amongst that are affected by turner syndrome. Each person who has turner syndrome all vary in their clinical phenotype. There has been increasing interest in this field because of the introduction in the treatment of turner syndrome with growth hormone. There has been improvement in the understanding of this condition because of the use of molecular genetic techniques. However, there still requires more work in this field. A multidisciplinary approach to treatment is important to improve the quality of life of girls with Turner Syndrome.

The arrow indicates the presence of only one X chromosome in Karyotype

History

Epidemiology

Turner Syndrome affects about 1 in 2000 live-born females. There are three types of karyotypic abnormalities but the most frequently seen is where the entire X chromosome is missing resulting in 45 X karyotype. The remaining third have structural abnormalities of the X chromosomes, and two thirds are mosaics. Whereby, the maternal X is retained in two-thirds of women and the paternal X in the remainder. The phenotype of Turner Syndrome is varies but it involves anomalies of the sex chromosome. It could be caused by the limited amount of genetic material in these abnormal chromosomes. Turner Syndrome can be transmitted from mother to daughter, and thus can it could be described as a heredity linked syndrome.

The loss of one of the sex chromosomes of turner syndrome occurs after the zygote has formed or just after the fusion of the gametes. In 70-80% of cases the retained X is from the mother. In such circumstances has lead to the different phenotypic expression of the genes present on the X chromosome depending upon if it came from the mother or father. The morphological differences from those retaining the maternal compared to retaining the paternal X is have shown to have a greater incidence of cardiovascular anomalies and neck webbing. The missing sex chromosome could be either an X or a Y. This has clinical implications because if the Y material is present there is a risk of up to 30% of gonadoblastoma developing in the dysgenetic gonads. This is because the 'gonadoblastoma locus' is on the Y chromosome which is believed to be situated on the long arm of the Y just below the centromere. Another factor affecting the phenotype in Turner syndrome is the inactivation of the abnormal X chromosomes. In a normal fetus there should be only one X chromosome that is active in each cell.

Abnormalities associated with Turner Syndrome

Etiology

Clinical manifestations

Turner syndrome is associated with a cognitive phenotype. This includes a low IQ score, nonverbal learning disability, visuoperception deficit and attention deficity disorder. Problems with nonverbal learning involve the difficulty in mathematics. When calculating they are slow. Difficulty in both visuoperception and visuo-constructional tasks is observed when identifying and locating becomes difficult due to poor visual working memory. One other contributing factor to this is the delay in selecting visuospatial tasks. The incidence rate of attention skills and impulsivity in girls with turner syndrome is higher then children in the general population with ADHD.

Diagnostic Procedures

Treatment

The most common abnormality is short stature as bone age is delaged due to the lack of estrogen. This could be treated with the completion of growth hormone therapy.

For young girls use a low dose of natural estrogen to promote and maintain secondary sex characteristics. However recommended to be used when she is approaching puberty in terms of social circumstances as physical sex appearance becomes apparent among her peers.

Evaluation and Management for Turner Syndrome

MANAGEMENT	METHOD	FEATURE
Orthopedic evaluation	Physical examination	Congential hip dislocation
Cardiac evaluation and management	Echocardiogram	BAV or COA
renal anatomy evaluation	Renal ultrasound	Rotational abnormalities
Blood pressure	Physical examination	Hypertension
Speech	Speech therapist	Hypertension
Speech	Speech therapist	Speech loss
Inner ear	Therapist	Hearing loss
Outer ear	Observation	Malformation of the outer ear
Middle ear	Ventilation tubes	Otitis media
Thyroid function	Levels of TSH	Primary hypothyroidism
Hearing	Karyotyping	Hearing problems
Plastic surgery	Elective surgery	Keloid
Vision	Physical examination	Ptosis
Orthodontic exam	Orthodontist	Dental abnormalities
Weight	Counselling	Obesity
Lyphedema	Therapy	Occur and recur at any age
Glucose intolerance	Growth promotion	Diabetes

Current/future research possibilities

Glossary

References