Turner syndrome

    Last updated date: 08-Jun-2023

    Originally Written in English

    Turner syndrome

    Turner syndrome


    Turner syndrome (TS) is a neurogenetic condition that is distinguished by partial or complete monosomy-X. TS is related with various physical and biological characteristics such as estrogen deficit, low height, and a higher risk for a variety of ailments, the most serious of which are heart issues. To address low stature and estrogen deficit, girls with TS are routinely treated with growth hormone and estrogen replacement therapy.

    The cognitive-behavioral phenotype linked with TS includes linguistic domain strengths as well as visual-spatial, executive function, and emotion processing deficits. The short stature homeobox (SHOX) gene has been discovered as a potential gene for short stature and other skeletal abnormalities linked with TS, however the gene or genes related with cognitive deficits are presently unclear.

    However, tremendous progress in understanding the neurodevelopmental and neurobiologic mechanisms causing these abnormalities has been accomplished, and promising therapies are on the horizon. Less is known about psychosocial and mental functioning in TS, however this paper suggests important features of psychotherapy treatment strategies. Continued genetic studies, such as microarray analysis, and the identification of potential genes for both physical and cognitive traits, should be part of future TS research.


    Turner syndrome definition

    Turner syndrome definition

    Turner syndrome (TS) is a complicated condition characterized by whole or partial monosomy of the X chromosome, which is often caused by a rare chromosomal nondisjunction. TS is one of the most frequent sex chromosomal disorders, affecting around one in every 2,000 live born girls. Short height, ovarian failure, webbed neck, heart problems, reduced glucose tolerance, thyroid illness, and hearing loss are among physical phenotypes linked with TS.

    There is substantial phenotypic variation, with low stature and gonadal dysgenesis being the most constant. As a result, growth hormone and estrogen replacement therapy are used to treat the vast majority of females with TS.



    According to the research, Turner syndrome affects around 1 in 2000 to 1 in 2500 live female newborns. However, the real frequency is unknown since many people with a moderate phenotypic go untreated or are discovered later in life. Turner syndrome occurs relatively uniformly across ethnicities and regions. 

    The prevalence of Turner syndrome at birth is decreasing due to increasing knowledge of prenatal ultrasound scans; this is because some moms carrying fetuses with Turner syndrome opt to terminate the pregnancy.



    Turner Syndrome Etiology 

    In females, Turner syndrome is caused by a deletion or non-functioning of one X chromosome. Monosomy X affects almost half of the Turner syndrome population (45, XO). The remaining 50% of the population has a mosaic chromosomal component (45, X with mosaicism).

    Some types of anomalies in the X chromosome that can lead to a nonfunctioning X chromosome are as follows:

    • Isochromosome Xq, which has two copies of the chromosome's long arm that are joined head to head.
    • Ring chromosome, in which a portion of the ends of the X chromosome's short and long arms are absent Xp or Xq deletion, in which a portion of the X chromosome's short arm is deleted.


    Some Turner syndrome patients may have Y chromosomal mosaicism. Although not a cause of Turner syndrome, the SHOX (short stature homeobox-containing gene on the X-chromosome) gene is linked to Turner syndrome's low stature. Turner syndrome is not normally inherited, but rather occurs as a result of a chance incident during reproduction.



    The majority of cases of Turner syndrome are not hereditary. When monosomy X is the cause, the chromosomal aberration occurs at random during the development of reproductive cells in the person's parent. Nondisjunction is a type of cell division defect that can result in reproductive cells with an incorrect number of chromosomes.

    Nondisjunction, for example, can result in the loss of a sex chromosome from an egg or sperm cell. If an unusual reproductive cell contributes to a child's genetic composition, each cell will have only one X chromosome and the other sex chromosome will be absent.

    Mosaic Turner syndrome is not a hereditary disorder either. It develops as a result of a random occurrence during the cell division stage of the afflicted individual's early fetal development. As a result, some of a person's cells have two sex chromosomes, whereas others only have one copy of the X chromosome. Other sex chromosomal defects in females with X chromosome mosaicism are conceivable. Turner syndrome can be caused by a partial deletion of the X chromosome, which can be passed down from generation to generation.


    Clinical presentation 

    Turner Syndrome Clinical Presentation 

    Prenatal ultrasound evidence of increased nuchal translucency, nuchal cystic hygroma, coarctation of the aorta/left-sided cardiac abnormalities, brachycephaly, horseshoe kidney, polyhydramnios, oligohydramnios, or non-immune fetal hydrops can all be used to diagnose Turner syndrome.

    Turner syndrome can manifest as congenital lymphedema of the hands and feet, a webbed neck, nail abnormalities, a narrow and high-arched mouth, and short fourth metacarpals or metatarsals in female newborns. The females grow into small height, a "shield" chest with widely separated nipples, a webbed neck, a low hairline at the base of the neck, cubitus valgus, and Madelung deformity of the forearm and wrist.

    Turner syndrome patients often have normal intellect but may have particular neurocognitive abnormalities, such as difficulty with visuospatial organization. This condition can raise the chance of learning problems, particularly those affecting math, memory, and attention. Females in adolescents frequently appear with delayed puberty or primary amenorrhea as a result of early ovarian failure. Turner syndrome is distinguished by "streak gonads." These are the ovaries, which are mostly connective tissue with no or only a few atretic follicles.

    Patients with Turner syndrome are also at a higher risk of developing cardiovascular abnormalities, which increases their chance of death. Aortic valve abnormalities (mainly bicuspid aortic valve), protracted transverse aortic arch, and pulmonary venous anomalies are among the cardiac malformations.

    Aortic dissection raises the chance of mortality in these individuals much more. Hearing loss is prevalent as a result of either recurrent otitis media, which causes conductive hearing loss, or a deficiency in the outer hair cells of the cochlea, which causes sensorineural hearing loss. Renal anomalies such as collecting system malformations, positional abnormalities, and horseshoe kidneys are frequent in Turner syndrome.

    Turner syndrome can cause nearsightedness or farsightedness, strabismus, amblyopia, epicanthic folds, ptosis, hypertelorism, and red-green color blindness. Turner syndrome increases the likelihood of developing autoimmune illnesses such as hypothyroidism, celiac disease, and inflammatory bowel disease. Females with Turner syndrome are more likely to develop gonadoblastoma due to the existence of dysgenic gonads.


    Females who are affected may also be prone to middle ear infections (otitis media), particularly during infancy and early childhood. Chronic otitis media may be associated with hearing loss owing to sound wave obstruction (conductive hearing loss). This hearing loss normally improves as a kid grows older and ear infections become less common. Hearing problems in early children might interfere with or delay speech development. Hearing loss in adults can arise and increase with age owing to a reduced capacity of the auditory nerves to transfer sensory data to the brain (sensorineural hearing loss).

    Certain Turner syndrome patients appear to be at higher risk than the general population for getting certain conditions such as diabetes, Celiac disease, and osteoporosis. Osteoporosis is defined by a general decrease of bone density, which might increase the risk of fractures. Gastrointestinal issues, including as eating difficulty and gastroesophageal reflux disease (GERD), may also arise.



    Turner Syndrome Diagnosis

    Turner syndrome can be detected prenatally by chorionic-villus sample or amniocentesis. When a prenatal ultrasound reveals fetal hydrops, cystic hygroma, or heart abnormalities, Turner syndrome should be suspected. After delivery, karyotype testing is required to confirm the diagnosis.

    If there is mosaicism, the karyotype can occasionally be normal, and if there is a strong suspicion, a FISH investigation is a possibility in addition to the karyotype. In patients with the above-mentioned clinical symptoms, genetic testing with karyotype analysis is required to confirm the diagnosis. The first step is to analyze the karyotype of peripheral blood mononuclear cells.

    Patients in adolescents might appear with either delayed puberty or amenorrhea. Elevated follicle-stimulating hormone (FSH) levels are associated with Turner syndrome, and anti-Mullerian hormone (AMH) may be a more sensitive diagnostic for predicting ovarian failure. If the initial karyotype in a patient with clinically suspected Turner syndrome is normal, a second karyotype utilizing a different tissue, such as skin, buccal mucosa cells, or bladder epithelial cells, should be conducted.

    Following a Turner syndrome diagnosis, patients are evaluated for any related abnormalities such as heart anomalies, renal anomalies, and learning difficulties. Screening should be part of the initial examination, and patients should be screened on a regular basis after that. Patients should have renal ultrasonography and cardiovascular examination, including echocardiogram in babies and children and MRI in older girls and women, at the time of first diagnosis.

    Some of the screening laboratory tests include:

    At the age of four and up, serum TSH is used to test for autoimmune thyroiditis, while tissue transglutaminase with total IgA is used to screen for celiac disease.

    Fasting blood glucose, glycated hemoglobin, ALT, AST, serum creatinine, and urinalysis at ten years of age and older to screen for diabetes mellitus, fatty liver disease, and kidney disease.



    Short Stature

    Girls with Turner syndrome are often short-statured, and their growth must be closely monitored. Turner syndrome does not result in a lack of growth hormone. However, the patients react well to growth hormone therapy and should begin treatment with growth hormone as soon as their height falls below 5% for their age. If not treated properly, the adult height is estimated to be 20 cm lower than the typical adult female height.

    Growth hormone therapy should be continued until the patients attain adult height and no longer have any potential for growth. When a patient is on growth hormone therapy, it might occasionally reveal underlying scoliosis. As a result, patients' spines should be continuously checked during therapy. Patients who develop scoliosis should be sent to orthopedic surgery for bracing or corrective surgery.

    Other potential side effects of growth hormone therapy include intracranial hypertension, slipping capital femoral epiphyses, and pancreatitis. Pubertal induction can be administered if the patient requires further growth support in addition to growth hormone, oxandrolone, or delayed development. 



    Turner syndrome is usually accompanied with cardiac problems. A cardiologist should perform an EKG on the patient at the time of diagnosis to check for a prolonged QT interval. Blood pressure should be taken in both the upper and lower limbs, and patients should have an echocardiography or cardiac MRI to rule out any cardiac abnormalities.

    Antiarrhythmics, macrolide and fluoroquinolones, metronidazole, certain antifungals and antiretrovirals, and psychiatric medicines should be avoided if the QT interval is extended. Coarctation of the aorta need surgery to rectify. Patients must be monitored for aortic dilatation using echocardiograms or cardiac MRI throughout their lives. Blood pressure should be kept within normal limits to reduce the risk of aortic dilatation and dissection. Beta-blockers should be used initially to manage blood pressure, followed by an ACE inhibitor. 


    Cognitive function/learning disabilities

    Girls with Turner syndrome frequently have learning impairments while having normal IQ, which may necessitate special education and school evaluations.


    Hearing loss

    Regular hearing monitoring, including serial audiology assessments, is advised throughout life, with an audiology evaluation suggested every three years in children and every five years in adults.




    At the time of diagnosis, a renal ultrasound is required. Renal anomalies, such as collecting system malformations, positional/horseshoe kidneys, and mal-rotated kidneys, are common in Turner syndrome. Obstruction caused by ureteropelvic junction anomalies can result in hydronephrosis and raise the risk of pyelonephritis. If any abnormalities are discovered, the patient should be referred to nephrology.


    Ovarian Failure

    Turner syndrome often manifests as primary amenorrhea or delayed puberty due to early ovarian failure in girls. Serum FSH and AMH levels should be tested between the ages of 10 and 11 years. Serum AMH levels can be used to predict ovarian function, and individuals with measurable levels are more likely to have spontaneous puberty. If no breast growth occurs between the ages of 11 and 12, estrogen replacement treatment should be initiated.

    Estrogen treatment is required for almost all Turner syndrome females, even if they undergo spontaneous puberty, which may last for a while but is generally followed by primary ovarian insufficiency. Later in the treatment, cyclic progestins are added to the regimen to promote cyclic uterine bleeding and avoid endometrial hyperplasia. If gonadotropins are elevated or AMH levels are low, estrogen treatment should be started around the age of 11 to 12 years old. The therapy can begin with dosages ranging from 1/10 to 1/8 of an adult replacement dose and be gradually raised every six months to mimic normal pubertal progression until achieving adult dosing.

    Patients with Turner syndrome may be able to cryopreserve ovarian tissue or oocytes. This option is only available to people who have signs of ovarian function and should not be used before the age of 12 years. Most women with Turner syndrome are infertile due to ovarian follicular loss. To conceive, in vitro fertilization using donor oocytes is one possibility.


    Osteoporosis / Bone Health

    Turner syndrome patients are more likely to have reduced bone mineral density and fractures. Estrogen treatment, as well as extra vitamin D and calcium, reduces their risk. Turner syndrome increases the chance of scoliosis, and patients should be screened annually and every six months if they are on growth hormone therapy.


    Screening for other comorbidities

    • Celiac disease – Immunoglobulin for tissue transglutaminase A antibodies should be measured around the age of two, and then every two years for the rest of the child's life.
    • Autoimmune thyroiditis – TSH and free or total T4 should be measured annually, beginning around four years.
    • Liver disease – After the age of ten, ALT, AST, GGT, and alkaline phosphatase levels should be checked yearly. These labs are normally raised in Turner syndrome, but if they persist and are greater than twice normal, a hepatologist should be consulted.
    • Metabolic syndrome – To screen for hyperglycemia, hemoglobin A1c should be checked yearly beginning at the age of 10. If a patient has at least one cardiovascular disease risk factor, a lipid panel should be measured yearly to test for dyslipidemia.
    • Vit D deficiency – Serum 25-hydroxyvitamin D should be measured between 9 to11 years of age and every 2 to 3 years thereafter.
    • Gonadoblastoma – Patients with Turner syndrome who have virilization or have marker chromosomal elements on their karyotype should be tested for the Y chromosome. If the Y chromosome is present, the gonads should be removed; otherwise, the chance of gonadoblastoma rises.


    Differential Diagnosis

    Noonan syndrome is a disorder that is quite similar to Turner syndrome and can be difficult to differentiate. Noonan syndrome is distinguished by clinical features such as a webbed neck, small height, cardiac and renal problems.

    There is no chromosomal defect in Noonan syndrome, as opposed to Turner syndrome, which has a missing or non-functioning X chromosome. As a result, Noonan syndrome affects both males and females, whereas Turner syndrome affects exclusively females. To distinguish between these two disorders, genetic testing is essential.


    Noonan syndrome

    Noonan syndrome is a common genetic condition that usually manifests itself at birth (congenital). The condition is distinguished by a wide variety of symptoms and physical manifestations that vary widely in range and severity. Many afflicted people have a characteristic facial look, a wide or webbed neck, a low posterior hairline, a classic chest deformity, and small height.

    Widely set eyes (ocular hypertelorism); skin folds that may cover the inner corners of the eyes (epicanthal folds); drooping upper eyelids (ptosis); a small jaw (micrognathia); a depressed nasal root; a short nose with broad base; and low-set, posteriorly rotated ears are all characteristics of the head and facial (craniofacial) area (pinnae). Distinctive skeletal deformities, such as anomalies of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows, are also common (cubitus valgus).

    Many Noonan syndrome newborns also have heart (cardiac) problems, such as a restriction of appropriate blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, learning difficulties or mild intellectual disability, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings are possible.

    Noonan syndrome is an autosomal dominant genetic condition produced by changes (mutations) in the rasopathy pathway's many single genes. Some Noonan syndrome symptoms may appear to be similar to those of Turner syndrome (due to certain findings that may be associated with both disorders, such as short stature, webbed neck, etc.).

    As a result, Noonan syndrome has been called "male Turner syndrome," "female pseudo-Turner syndrome," or "Turner phenotypic with normal chromosomal karyotype" in the past. However, there are several distinctions between the two illnesses. Noonan syndrome affects both men and women, and the chromosomal composition is normal (karyotype). Turner syndrome, which is characterized by X chromosomal abnormalities, affects only females.



    Turner syndrome patients have a threefold increase in mortality compared to the general population. Cardiovascular disease caused by coronary heart disease and stroke is a substantial risk factor in elderly people. The most common cause of congenital cardiovascular disease is an aortic aneurysm. Patients also have a higher death rate owing to pneumonia, diabetes, epilepsy, liver illness, and renal disease.



    There has been significant progress in characterizing the cognitive-behavioral, neurobiologic, endocrinologic, physical, and genetic aspects linked with Turner syndrome. However, there are numerous unanswered questions. Existing research have often used small sample numbers, wide age spans, and mixed genotypes. Smaller sample numbers obviously pose challenges in terms of power and generalizability.

    The ability to evaluate how hormone replacement therapy, particularly estrogen treatments, effect outcome in TS is hampered by large age variations. There have also been no investigations on the gene expression patterns of girls with X monosomy and TS. To explore gene expression profiles in girls with TS and identify possible candidate genes underlying the cognitive-behavioral deficits associated with TS, studies utilizing genetic analysis such as microarray technologies will be required.

    Continued research into X-linked genes that resist inactivation and have Y chromosomal homologues will also be critical in finding potential genes implicated in the cognitive-behavioral and physical characteristics of TS.