Phys final - turner syndrome.pdf

Turner Syndrome Definition: Turner syndrome (TS) refers to the wide spectrum of phenotypic and functional abnormalities that result from the presence of complete or partial monosomy of the X chromosome in a phenotypic female....

Turner Syndrome Definition: Turner syndrome (TS) refers to the wide spectrum of phenotypic and functional abnormalities that result from the presence of complete or partial monosomy of the X chromosome in a phenotypic female. o The defining clinical triad is: § short stature § impaired sexual development § infertility. o Dr. Henry Turner, an internist at the University of Oklahoma, first described a set of common physical features in seven of his patients in a report published in1938. § However, the chromosomal abnormality that defines TS was not discovered until 1959, when technology to perform karyotyping became available. ○ · Prevalence: o Monosomy of the X chromosome is one of the most common chromosomal abnormalities observed in human embryos and fetuses, but 99% of these conceptuses miscarry during the first trimester of pregnancy. o Up to 15% of all spontaneous abortions manifest this aberration. o While the frequency of TS varies in the medical literature, several reputable sources indicate that TS occurs in 1 in 2,000–3,000 live female births. o No racial or ethnic predilections have been established, and TS occurs exclusively in females. ○ · Approximately 60,000 girls and women are currently affected in the United States, with 800 new cases being diagnosed annually. o Approximately half of women with TS lack an entire X chromosome. o Approximately 30% display structural aberrations of the X chromosome (e.g., deletion of a significant segment of the X chromosome) and another 20% are mosaics (i.e., some cells contain a normal XX complement). ○ · Patients have a higher risk than the general population for serious diseases such as: o diabetes mellitus o Neuroblastoma o Hypertension o Dyslipidemia—all of which can have a significant impact on life expectancy. ○ · Because the chronic nature of the disease requires lifelong medical attention, expensive supportive and symptomatic therapy, and specialized care, TS imposes a significant burden on the healthcare delivery system of the United States. ○ · At fertilization, when such gametes fuse with normal haploid gametes (23 chromosomes), the resulting zygotes are monosomic (45 chromosomes) like TS or trisomic (47 chromosomes).  o Since approximately two of three recognized 45,X conceptions inherit a maternal X chromosome, most cases of TS are caused by paternal meiotic errors. o Furthermore, many of the clinical features of TS are due to the lack of a second SHOX gene, which is located on the X chromosome. o Pathophysiologic alterations in the ovaries of women with TS represent an acceleration of the normal aging process within these organs. ○ · Diagnosis: Clinical Manifestations and Laboratory Tests: o A cytogenetic analysis of blood cells that reveals the classic 45,X karyotype or one of the variants of TS establishes the diagnosis. § Variants include 46,X (abnormal X), 45,X/46,XX mosaicism, and 45,X/46,XY mosaicism. o Clinical manifestations are many. However, some of the more common features are: § short stature with normal body proportions (the mean predicted height is 4’9” virtually all TS women remain less than 5 feet in height without treatment) § primary amenorrhea with delayed puberty (80%) or secondary amenorrhea (20%) § renal abnormalities (60%), such as horseshoe kidney § short fourth metacarpal bones (50%) § webbing of the neck (40%) § hypertension (40% of adults and 20% of girls) § bicuspid aortic valve (33%) § coarctation (i.e., localized narrowing) of the aorta (15%) § high-arched palate § widely space nipples § pigmented nevi (i.e., moles) § characteristic facial abnormalities, such as small mandible, prominent ears, and epicanthal folds § hyperconvex nails § More than 95% of adult women exhibit short stature and infertility. ○ · Often the absence of menarche first causes the individual to seek medical attention. o As a result, it has been suggested that girls with: o unexplained short stature (i.e., height below the fifth percentile) o webbed neck o peripheral lymphedema o coarctation of the aorta o delayed puberty have chromosome tests done. o Chromosome analysis should also be considered for girls whose height is above the fifth percentile but who have two or more features of TS ○ · Serious Complications and Prognosis:  o Limited epidemiologic studies suggest that life expectancy is decreased by approximately 10 years, in part the result of an increased risk for major complications. o The most serious complications of TS are chronic illnesses that often develop in monosomic X patients. o These include: § diabetes mellitus § Dyslipidemia § Hypertension § rheumatoid arthritis § inflammatory bowel disease § Hashimoto thyroiditis (a common cause of hypothyroid disease) § Cataracts § Type of brain cancer known as Neuroblastoma. o However, with good medical care, the prognosis for a near-normal life with a productive career is excellent. o Although infertility is a common complication, reproductive technologies have enabled women with TS to bear children. § A donor egg is used to create the embryo and the TS woman carries the embryo to term.