Genetics
diagnostics powering improved clinical outcomes
Turner Syndrome
Our method for detecting TS and other sex chromosome abnormalities employs highly informative single nucleotide polymorphism (SNP) markers from specially selected regions of the X- and Y-chromosomes, matched with an elegant, proprietary and quantitative method of genotyping.
We are engaged in clinical trials of girls referred from short stature clinics at Yale and other pediatric endocrinology centers. These trials are supported by an SBIR Phase II grant to the Company (R 42 HD 049230-02). This grant also funded our application and approval for Yale Human Investigation Committee protocol number 0705002658, “Screen for Turner Syndrome”, procedures, consents and age-appropriate assent forms, lease of laboratory space, purchase of dedicated equipment, development of a Yale HIC-approved secure database, development of a home/office TS kit for specimen collection, the hiring of knowledgeable lab personnel and the hiring of a dedicated pediatric nurse-practitioner for enrolling subjects.
Our data have shown less than 1% false negative results and specificity and accuracy comparable to the karyotype. This test is ready to be introduced to the market as a reliable screening test for suspected Turner syndrome cases.
Turner Syndrome (TS) is a chromosome abnormality affecting about 1 in every 2,000 female births and up to 10% of miscarriages. This abnormality, also called monosomy X, is the absence of all or part of one sex chromosome; it is denoted medically as 45X (older literature used XO), as opposed to the usual normal 46,XX female Karyotype.
The primary physical manifestation of this condition is short stature and under-developed sexual organs. The average TS patient is shorter at birth: 18.5” vs. 20” for healthy female infants and reaches only 4’6” at adulthood. The TS patient is treated with growth hormone therapy until they reach puberty. TS girls may also suffer from heart abnormalities, mild hearing loss and learning disabilities.
More than 90% of TS girls will fail to develop normal secondary sexual characteristics and menstruate due to some degree of ovarian failure. Most TS girls will require estrogen from puberty until the normal age of menopause. Estrogen replacement therapy is necessary for breast development, feminine body contours, menstruation and proper bone development. Fertility without assisted reproduction therapy is rare.
Treatment
Almost all patients with Turner Syndrome undergo Growth Hormone therapy prior to puberty. There is clear clinical evidence that final height could be almost normalized IF treatment with Growth Hormone (GH) is started early (age 4-6). Other studies have point to 2 key factors in achieving
normalized height:
1) Early start of Growth Hormone treatment
2) Escalating dose of GH
There is a finite window of opportunity for GH treatment that closes by the time the patient reaches puberty at around 12 years old. Therefore it is critical to diagnose this condition early to provide adequate time for GH therapy to address short stature in these girls.
Failure in most TS patients necessitates the need for estrogen replacement therapy at or around age 12 or when most girls enter puberty to prevent social problems due to delays in physical and psychological development. Almost all TS patients are infertile and will require estrogen therapy for the duration of their life.
Increases in morbidity and mortality seen in about 25% of TS patients is almost exclusively related to abnormal heart conditions such as coarctation of the aorta and abnormal bicuspid valves. Other cardiovascular conditions seen in TS patients include hypertension, dilated ascending aorta and hypo-plastic aortic arch. Cardiovascular risk of TS patients should be monitored at regular intervals using EKGs, MRIs, vascular scabs and blood pressure monitoring.