Clinical Features Of Turner Syndrome Research Articles

Similar Pattern of Increase in FIX Levels in Female Carriers and Males with Hemophilia B Leyden

Hemophilia B is a congenital X-linked recessive bleeding disorder that occurs as a result of mutations at the long (q) arm of the X chromosome at position 27. Hemophilia B affects 1 in 30,000 males; however the incidence in Ireland is more than double the international incidence and affects 1 in 12,500 male births. Hemophilia B Leyden is a sub-type of hemophilia B first recognized in 1970 in Leyden in the Netherlands. There are more than 20 genetic mutations that result in hemophilia B Leyden. These mutations cluster at three regions within the proximal promoter region of the F9 gene including mutations in nucleotides c.-34 and c.-35 (-5 and -6 legacy numbering) in almost half the cases, mutations around nucleotide c.-49 (-20) and mutations around nucleotide c.-19 (+10). Point mutations associated with hemophilia B Leyden interfere with F9 gene transcription via binding of F9 promoter to ONECUT1 in patients with c.-35 mutation, HNF4a (hepatocyte nuclear factor 4 alpha) in patients with c.-19 mutation and C/EBPa (enhancer-binding protein alpha) in patients with c.-49 mutation. A characteristic feature of hemophilia B Leyden is progressive rise in FIX:C level from the time of puberty to reach lower normal level in young adults. This led to the widely accepted believe that the increase in FIX:C level in hemophilia B Leyden is due to the effect of the androgens surge at puberty. Androgens and anabolic steroids were used for prophylactic treatment in patients with hemophilia B Leyden in a limited number of patients. Recent evidence from animal studies using hypophysectomized hemophilia B Leyden mouse model convincingly demonstrated the pre-eminent role of growth hormone (GH) in regulating the age-dependent increase in FIX:C levels. FIX:C levels were only restored to 10% of pre-hypophysectomy levels by exogenous administration of dihydrotestosterone or oestrodiol but were restored to 80% of pre-hypophysectomy levels by exogenous administration of GH. We investigated the pattern of the increase in FIX:C in 14 male children and four female children from seven different Irish families attending the National Haemophilia Centre at Children's Health Ireland, Crumlin. The hemizygous presence of hemophilia B Leyden associated variant c.35G>A was confirmed by standard dideoxysequence analysis in all children. To evaluate the timing of increase in plasma FIX:C levels, we measured FIX:C levels using automated one stage assay. Serial measurement of FIX:C in male children with hemophilia B leyden demonstrated an increase of FIX:C from severe/moderate levels at the first year of life to mild FIX:C levels within the first 3 years of life. In all 14 male children with hemophilia B Leyden, FIX:C levels increased gradually throughout childhood with more pronounced increase in FIX:C at the time of puberty (Figure 1-A). The increase in FIX:C levels coincided with the known physiological increase in GH levels. Growth hormone level is low during infancy and increases but remains stable at low levels during early childhood, until just before puberty when GH secretion surges to the highest lifetime peak. All four female carriers of hemophilia B Leyden showed low levels of FIX:C at diagnosis associated with variable bleeding symptoms (Figure 1-B). One female child had very low FIX:C level at diagnosis in the moderate hemophilia range (0.04 iu/ml), while all other three female children had low FIX:C levels at the mild hemophilia range at diagnosis (0.13 iu/ml, 0.27 iu/ml and 0.46 iu/ml respectively). Low FIX:C level in those female carriers is likely due to skewed inactivation of the unaffected X chromosome during embryogenesis (lyonization) as no child had compound heterozygosity for the F9 gene mutation and none of the children showed clinical features of Turner syndrome or testicular feminization syndrome. Serial measurement of FIX:C levels in those symptomatic female carriers of hemophilia B Leyden showed similar gradual increase in FIX:C levels during childhood with more steep increase at puberty. Our findings further assert that gender and sex hormones has no influence in the increase of FIX:C level in hemophilia B patients. Figure 1 Disclosures Nolan: Sobi: Other: personal fees; Bayer, CSL Behring, and Sanofi.: Other: sponsorship; Sanofi: Other: PI for sponsor-(Sanofi-) led clinical trial.

Can Brain Natriuretic Peptides and Osteoprotegerin Serve As Biochemical Markers for the Detection of Aortic Pathology in Children and Adolescents with Turner Syndrome?

Turner syndrome (TS) is a chromosomal disorder that affects 1:2,000 females. It results from either the complete or partial loss of the X chromosome as well as other aberrations. Clinical features of TS include short stature, delayed puberty, and congenital cardiac malformations. TS children also have an increased prevalence of cardiometabolic risk factors, which predisposes them to complications like coronary artery disease, cerebrovascular-related deaths, and aortic dissection. Early cardiac imaging, such as echocardiography and cardiac magnetic resonance imaging, are recommended to detect underlying aortic pathology. However, these modalities are limited by cost, accessibility, and are operator dependent. In view of these shortcomings, alternative methods, like vascular biomarkers, are currently being explored. There are only a few studies that have examined the relationship between B-type natriuretic peptide (BNP), N-terminal pro BNP (NT pro-BNP), and osteoprotegerin (OPG) and aortic disease in TS, and thus the data are only in proof-of-concept stages. Further meticulous longitudinal studies are required before BNP, NT pro-BNP, and OPG are used as vascular biomarkers for the detection of aortic disease in childhood and adolescent TS.

A New Case of Turner Syndrome with Early Pubertal Development

Turner syndrome (TS) is a relatively common chromosomal disorder caused by complete or partial X monosomy. The most frequently observed karyotype, 45, X, arises more often by loss of the paternal X or Y chromosome in meiosis or in early embryogenesis than by loss of the maternal X chromosome. The main clinical features of TS are short stature, gonadal dysgenesis, and not to undergo pubertal development (e.g. primary amenorrhea). However, a few rare cases of TS have shown precocious puberty. Our case of a 9-year-old girl did not have any TS-specific clinical hallmarks, with the exception of short stature. She visited our clinic because of her pubertal development and short stature. In this report, we highlight the variability that can occur in patients with TS and emphasizes the need to carefully assess unusual growth patterns in any child, regardless of other underlying conditions.

X‐linked Dystonia‐Parkinsonism manifesting in a female patient due to atypical turner syndrome

Recessive X-linked dystonia-parkinsonism almost exclusively affects men. We investigated the genetic mechanisms causing this disorder in a female patient. We confirmed the presence of an X-linked dystonia-parkinsonism-specific change in our patient by sequencing. In addition, we employed quantitative real-time PCR and array comparative genomic hybridization to determine the patient's X-chromosome copy number. The patient's sequence electropherogram suggested a higher amount of the mutated allele compared with the wild-type allele. Subsequently, extensive gene dosage analyses revealed a copy number of the X chromosomes between 1 and 2, indicating loss of 1 X chromosome in a subset of cells. Phenotypic reevaluation of the patient showed several clinical features of Turner syndrome. Our female X-linked dystonia-parkinsonism patient suffered from an undiagnosed X-chromosome monosomy in a subset of cells (45,X/46,XX), suggesting an atypical Turner syndrome and contributing the first molecular explanation for the manifestation of an X-linked dystonia-parkinsonism phenotype in women. © 2013 Movement Disorder Society.

Otologic and Audiologic Characteristics in Children with Turner Syndrome

Background and ObjectivesZZTurner syndrome (TS) is known to be caused by a total or partial deletion of one X-chromosome. Besides short stature and failure to enter puberty due to ovarian dysgenesis, auricular malformations, middle ear diseases and hearing impairment are also other clinical features of Turner syndrome. The goal of this study is to report otologic and audiologic characteristics in a group of children with Turner syndrome and correlate with these find

Gender Role Development in Two Clinical Syndromes: Turner Syndrome Versus Constitutional Short Stature

Turner syndrome (TUS) in girls causes sex chromosome abnormalities, ovarian dysgenesis with estrogen deficiency, and short stature. The goal of this study was to assess the long-term effects of sex chromosome and hormonal anomalies on female gender role development. The authors report data from an interview assessing gender role development in 23 TUS women, compared with 23 closely matched women with constitutional short stature and with 10 normal sisters of the TUS women. The results show more stereotypic feminine behavior in childhood, adolescence, and adulthood in the TUS subjects. The authors conclude that the clinical features of TUS do not impede normal female gender development. Furthermore, the data suggest that the tendency to greater femininity in TUS women cannot be explained solely by short stature and may be related to other psychosocial, endocrine, or brain effects of the syndrome.