Early Diagnosis Of Turner Syndrome Research Articles

Age at and indication for diagnosis of Turner syndrome in the pediatric population.

Early diagnosis of Turner syndrome (TS) enables timely intervention and may improve outcomes, but many are still diagnosed late. The objectives of our study were to describe the age and clinical features leading to diagnosis of TS in a large referral center. We hypothesize that newer testing modalities, such as noninvasive prenatal testing (NIPT), may lead to a decline in the age of diagnosis. Medical records of TS patients followed at The Cincinnati Center for Pediatric and Adult TS Care between 1997 and 2016 were reviewed for age at diagnosis, karyotype, and clinical indication(s). Patients (<18 years) were included (n=239). Thirty-seven percent of patients were diagnosed prenatally or neonatally (≤1month). The median age of diagnosis was 1.5 (IQR 0.0-10.0) years. If not made during those periods, the median age was 9.3 (IQR 3.2-12.5) years. The most common indications for diagnosis were before birth, unspecified prenatal testing (57%); in neonates/infants, lymphedema (21%); in childhood, short stature (72%); and in adolescence, short stature (45%) followed by pubertal delay with short stature (22%). The age of TS diagnosis in our cohort is young. However, when the diagnosis is not made before 1year, the median age of diagnosis has not changed in recent years. The age at diagnosis could decrease with prenatal testing, although our study may not have assessed a long enough period of increased use of NIPT. Together with an increase in provider clinical awareness, this may result in more age-appropriate screening of comorbidities and earlier therapeutic intervention.

Associated clinical abnormalities among patients with Turner syndrome.

OBJECTIVE:The early diagnosis of Turner syndrome (TS) is often difficult because of the various clinical features. This study aimed to investigate clinical features and identify associated abnormalities in a group of patients with TS.METHODS:Retrospective data of presenting clinical features collected from the medical records of the 37 patients with TS. All patients were examined for associated clinical abnormalities.RESULTS:Mean age at diagnosis was 9.3±4.1 years. The main reason for referral was short stature and/or delayed puberty. All of the patients had at least one dysmorphic sign. Skeletal system abnormalities (57%) were the most common associated abnormality, which was followed by gastrointestinal system problems (40%). Cardiac defects occurred in 32%. Urinary system abnormalities occurred in 27%. Dermatological problems were detected in 32% of the patients. The pathology of the hearing was found in 19%. Autoimmune thyroid disease was detected in 24% of the patients, and celiac disease was detected in 5.4% of the patients.CONCLUSION:Phenotypic variability often leads to a delay in the diagnosis of TS. Early diagnosis can initiate effective management in patients with TS.

Examination of sex chromosome abnormalities in childhood

Early diagnosis of sex chromosome abnormalities is important because of prevention, family planning and optimal therapy. Investigation of the relationship between phenotype, age at time of diagnosis and therapeutic options in sex chromosome aberrations. Processing data of 51 children with sex chromosome abnormalities who were diagnosed between 2009 and 2014 and examined at the 2nd. Department of Pediatrics, Semmelweis University, by the methods of anamnesis, family tree analysis, physical examination, karyotype analysis and fluorescent in situ hybridisation. 41% of the patients were diagnosed with Turner-, 18% with Klinefelter-, 10% with double-Y-, 6% with triple- and poly-X-syndrome, 19% with other gonadal dysgenesis and 6% with other abnormality. The average age at diagnosis: Turner- and Klinefelter-syndrome 10 years, other gonadal dysgenesis 9 years, 46,XX,t(X;10) 17 years, other abnormalities 1-2 years. Numerical aberrations of the sex chromosomes are more common than structural aberrations. Klinefelter-, triple- and poly-X-syndromes are underdiagnosed in childhood. Early diagnosis of Turner-syndrome and other gonadal dysgenesis is necessary to optimise therapy and prevent associated diseases. This can be achieved by modern prenatal diagnostic methods and targeted activity of family pediatricians. Orv Hetil. 2018; 159(27): 1121-1128.

FSH may be a useful tool to allow early diagnosis of Turner syndrome

BackgroundUltrasensitive assays to measure pre-pubertal gonadotropins levels could help identify patients with Turner syndrome (TS) in mid-childhood, but studies in this field are scarce. The aim of this study was to analyze gonadotropins levels in girls with TS throughout childhood.MethodsRetrospective longitudinal study conducted with 15 girls with TS diagnosed with < 5 years whose FSH and LH measures were available since then. Hormones were evaluated in newborn/mini-puberty (< 0.5 years), early childhood (0.5–5 years), mid-childhood (5–10 years) and late childhood/adolescence (> 10 years). In newborn/mini-puberty and late childhood/adolescence pre-pubertal or pubertal gonadotropins were considered normal; in early childhood and mid-childhood concentrations above the pre-pubertal range were considered abnormal.ResultsAbnormally high FSH alone was found in four of five patients in newborn/mini-puberty, 13 of 15 during early childhood and nine of 15 during mid-childhood. In the group of 12 patients in late childhood/adolescence, the three girls with spontaneous puberty had only normal levels; the remaining showed only post-menopausal concentrations. In mid-childhood one patient exhibited only pre-pubertal FSH. Conversely, most LH measurements in early and mid-childhood were normal.ConclusionKaryotyping of girls with short stature and high FSH levels would allow early diagnosis of Turner syndrome in a significant number of patients, particularly when resources for chromosome study of all girls with growth deficiency are limited.

Measured parental height in Turner syndrome\u2014a valuable but underused diagnostic tool

Early diagnosis of Turner syndrome (TS) is necessary to facilitate appropriate management, including growth promotion. Not all girls with TS have overt short stature, and comparison with parental height (Ht) is needed for appropriate evaluation. We examined both the prevalence and diagnostic sensitivity of measured parental Ht in a dedicated TS clinic between 1989 and 2013. Lower end of parental target range (LTR) was calculated as mid-parental Ht (correction factor 12.5 cm minus 8.5 cm) and converted to standard deviation scores (SDS) using UK 1990 data, then compared with patient Ht SDS at first accurate measurement aged > 1 year. Information was available in 172 girls of whom 142 (82.6%) were short at first measurement. However, both parents had been measured in only 94 girls (54.6%). In 92 of these girls age at measurement was 6.93 ± 3.9 years, Ht SDS vs LTR SDS − 2.63 ± 0.94 vs − 1.77 ± 0.81 (p < 0.001), Ht SDS < LTR in 78/92 (85%). Eleven of the remaining 14 girls were < 5 years, while karyotype was 45,X/46,XX in 2 and 45,X/47,XXX in 3.Conclusion: This study confirms the sensitivity of evaluating height status against parental height but shows that the latter is not being consistently measured.What is Known:• Girls with Turner syndrome are short in relation to parental heights, with untreated final height approximately 20 cm below female population mean.• Measured parental height is more accurate than reported height.What is New:• In a dedicated Turner clinic, there was 85% sensitivity when comparing patient height standard deviation score at first accurate measurement beyond 1 year of age with the lower end of the parental target range standard deviation.• However, measured height in both parents had been recorded in only 54.6% of the Turner girls attending the clinic. This indicates the need to improve the quality of growth assessment in tertiary care.

Clinical manifestation and cytogenetic analysis of 607 patients with Turner syndrome

To explore the correlation between cytogenetic findings and clinical manifestations of Turner syndrome. 607 cases of cytogenetically diagnosed Turner syndrome, including those with a major manifestation of Turner syndrome, were analyzed with conventional G-banding. Correlation between the karyotypes and clinical features were analyzed. Among the 607 cases, there were 154 cases with monosomy X (25.37%). Mosaicism monosomy X was found in 240 patients (39.54%), which included 194 (80.83%) with a low proportion of 45,X (3 ≤ the number of 45, X ≤5, while the normal cells ≥ 30). Structural X chromosome abnormalities were found in 173 patients (28.50%). A supernumerary marker chromosome was found in 40 cases (6.59%). Most patients with typical manifestations of Turner syndrome were under 11 years of age and whose karyotypes were mainly 45,X. The karyotype of patients between 11 and 18 years old was mainly 45,X, 46,X,i(X)(q10) and mos45,X/46,X,i(X)(q10), which all had primary amenorrhea in addition to the typical clinical manifestations. The karyotype of patients over 18 years of age were mainly mosaicism with a low proportion of 45,X, whom all had primary infertility. 53 patients had a history of pregnancy, which included 48 with non-structural abnormalities of X chromosome and 5 with abnormal structure of X chromosome. Generally, the higher proportion of cells with an abnormal karyotype, the more severe were the clinical symptoms and the earlier clinical recognition. Karyotyping analysis can provide guidance for the early diagnosis of Turner syndrome, especially those with a low proportion of 45,X.

Neonatal detection of Turner syndrome by real-time PCR gene quantification of the ARSE and MAGEH1 genes.

Turner syndrome (TS) is characterized by the presence of one full X chromosome and total or partial deletion of the second sex chromosome. Diagnosis of TS is often delayed, resulting in inappropriate treatment. Early diagnosis of TS using a neonatal screening test may improve preventive measures and treatment, thus improving patient quality of life. The goal of this study was to standardize a neonatal TS screening algorithm. Two study genes (ARSE and MAGEH1) and 1 normalizing gene (HBB) were used to detect the second X chromosome. We screened 996 newborns whose peripheral blood was collected and stored in filter paper. In addition, samples from 20 patients with confirmed diagnosis of TS were included in the study. Relative amounts of ARSE/HBB were determined using real-time polymerase chain reaction. The cutoff at the 5th percentile was arbitrarily set to indicate repetition of the test. The test was repeated in 51/1016 patients with ARSE/HBB < 0.81. For 10 samples with values persistently <0.81, we quantified the MAGEH1/HBB ratio. Values below the 95th percentile in TS patients (MAGEH1/HBB < 1.24) were considered to be inadequate. Only 6/996 NB showed inadequate values for the 2 studied genes, which were recalled for clinical evaluation and karyotype testing. Analysis of 20 patients diagnosed with TS allowed for identification of false-negatives and true-positives, establishing 95% sensitivity when the indicated cutoff values were used. In conclusion, our algorithm reached 95% detection sensitivity with an acceptable recall rate (0.6%), allowing for the detection of suspected TS cases in the neonatal period.

Spontaneous puberty in girls with early diagnosis of Turner syndrome

To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism.

Otolaryngologic markers for the early diagnosis of Turner syndrome

Objective To identify and characterize otolaryngologic markers for the early diagnosis of Turner syndrome (TS). Study design Prospective cohort survey. Methods Setting: Clinical Center of the National Institutes of Health (NIH). Patients: Ninety-one females, 7–61 years old (average = 28.7 y), enrolled in a multidisciplinary study of karyotype–phenotype correlations in TS. Main outcome measures: Age at diagnosis, X chromosome karyotype, history of chronic or recurrent otitis media (OM), sensorineural hearing loss (SNHL), palate dysmorphism, pinna deformity, pterygium colli, low posterior hairline, low-set ears, and micrognathia. Results Sixty-nine (76%) patients had a history of chronic or recurrent OM, 62 (68%) had a dysmorphic palate, 57 (63%) had SNHL, and 90 (99%) had one or more of these findings. 83 (91%; average age at diagnosis = 9.4 y) had one or more external craniofacial signs: pinna abnormalities, pterygium colli, low-set ears, micrognathia or a low posterior hairline. Eight patients (average age at diagnosis = 13.2 y) had no external craniofacial signs, although seven (88%) of these eight patients had a history of chronic or recurrent OM, dysmorphic palate or SNHL. The age at diagnosis was not significantly different between groups with or without external craniofacial signs ( P = 0.126). Conclusions Patients with mild or incompletely penetrant TS phenotypes often present with otitis media, hearing loss, or both before the diagnosis of TS is established. Palatal dysmorphism, including ogival morphology, is another otolaryngologic marker for TS. Prompt recognition of these manifestations of TS could hasten its diagnosis and appropriate medical care.

Metacarpophalangeal pattern profile analysis as a tool for early diagnosis of turner syndrome

To analyze the metacarpophalangeal pattern profile (MCPP) in a cohort of individuals with Turner syndrome (TS), and to assess its value as a tool for early diagnosis of TS. Medical records and radiological material were collected of 71 patients with TS aged between 3 and 21 years. Forty-six patients received growth hormone therapy (33-66 microg kg(-1) day(-1)) and 14 of these were also treated with the anabolic steroid oxandrolone (1.25-3.75 mg day(-1)). A total of 233 frontal hand radiographs were studied and pattern profiles were calculated. Profiles of the TS patients were compared with those of 70 normal females. Mean pattern profiles were calculated for different age groups and extrapolated profiles for newborns and infants were developed. Our results confirm that patients with TS have a distinct MCPP which differs significantly from that of normal individuals. A bone-shortening gradient with increasing shortening from distal phalanges to metacarpals was demonstrated. We also showed that the MCPP in TS is a remarkably constant feature from 3 to 18 years. Pattern profiles did not differ significantly between the patients with 45,X and non-45,X karyotype. MCPP was not affected by treatment with growth hormone of growth hormone plus oxandrolone. Discriminant analysis yielded correct classification in 88%, of analyzed cases. TS individuals have a distinct hand pattern profile that is not age-related. MCPP analysis can be applied at any age and may facilitate early diagnosis of TS. Our study showed that MCPP analysis is a specific and sensitive method that should be considered as a routinely used tool for early diagnosis of TS in girls with unexplained short stature.

Otolaryngologic markers for early diagnosis of turner syndrome

Problem: Turner syndrome (TS) affects up to one in 2,000 live female births and is characterized by the total or partial loss of one X chromosome in females with short stature and gonadal dysgenesis. Less penetrant features include sensorineural hearing loss (SNHL), otitis media (OM), pterygium colli, and craniofacial dysmorphism. We report the otolaryngologic features observed in a TS cohort. Methods: A cohort with a wide spectrum of phenotypic severity has been prospectively ascertained through a multidisciplinary study of genotype-phenotype correlation in TS at the National Institutes of Health. Subjects were evaluated by otolaryngologic examination, pure tone and speech audiometry, tympanometry, and stapedial reflex testing. Results: Ninety-nine TS patients (age range, 7 to 61 years; average, 30 ) with an average age at diagnosis of 10 years old (range, prenatal to 38 years) were studied. Sixty-three percent of the subjects had a high-arched or a peaked, ogival hard palate. Seventy-one percent had a history of recurrent OM and 64% had SNHL. Cross-sectional analysis revealed 2 predominant patterns of SNHL: adult-onset SNHL affecting high frequencies, and childhood-onset SNHL, initially affecting high or middle frequencies, with eventual progression to severe impairment across all frequencies. Conclusion: Diagnosis of TS is often delayed until the second decade or later. Almost all TS patients, even the least affected individuals with no external craniofacial stigmata of TS, had at least 1 of 3 otolaryngologic findings: recurrent OM, SNHL, and high-arched or ogival palate. Significance: The diagnosis of TS is often missed in female children presenting with OM and short stature. In association with a high-arched or ogival palate, or SNHL, these features are useful clinical markers for the initial detection and timely treatment of TS patients. Support: NIH intramural research funds Z01-DC-000064-03 and NICHD DIR Protocol 00-CH-0219.