Tumors of dysgenetic gonads in Swyer syndrome Zieliñska, Dorota; Zajączek, Stanislaw; Rzepka-Górska, Izabella
Journal of pediatric surgery,
10/2007, Letnik:
42, Številka:
10
Journal Article
Recenzirano
Abstract Background/Purpose The female with Swyer syndrome requires close follow-up because of the high risk of neoplastic transformation in the dysgenetic gonads. The aim of this work was to present ...our experience with tumors in patients with Swyer syndrome. Methods We studied 8 females with Swyer syndrome. At the time of diagnosis, they were 13 to 18 years old. We performed an ultrasound examination of dysgenetic gonads, hormonal (follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone) and genetic ( SRY , karyotype) tests, and histologic analysis of gonads (bilateral gonadectomy was performed in all patients). Results Gonadal tumors were found in 6 patients (3 cases of gonadoblastoma, 1 dysgerminoma, and 2 gonadoblastoma with dysgerminoma). Hormonal activity of gonadoblastoma was noted in 3 patients, with 1 tumor producing androgens. Conclusion Our data suggest that patents with gonadal dysgenesis and 46,XY karyotype should be referred for bilateral gonadectomy because of the high risk of neoplastic transformation. Estrogen-producing gonadoblastoma may mask gonadal dysgenesis and delay the diagnosis of this pathology.
Summary
Objectives Multisystem pseudohypoaldosteronism (PHA) is a rare autosomal recessive aldosterone unresponsiveness syndrome that results from mutations in the genes encoding epithelial sodium ...channel (ENaC) subunits α, β and γ. In this study we examined three PHA patients to identify mutations responsible for PHA with different clinical presentations.
Patients All three patients presented uniformly with symptoms of severe salt‐loss during the first week of life and were hospitalized for up to a year. Beyond infancy, one of the patients showed mild renal salt loss and had no lower respiratory tract infections until 8 years of age, while the other patients continue with a severe course.
Results We sequenced the complete coding regions and intron–exon junctions of the genes encoding α, β and γ subunits of ENaC for all patients. The results revealed that the mild case represents a novel compound heterozygote including a missense (Gly327Cys) mutation in the αENaC gene. Sequences of relatives over three generations confirmed that the missense mutation co‐segregates with PHA. This mutation was not found in 60 control subjects. The other patients with severe PHA had two homozygous mutations, a novel deletion mutation in exon 8 of the αENaC gene and a splice site mutation in intron 12 of the βENaC gene. Most of the PHA‐causing mutations appear in the αENaC gene located on chromosome 12 rather than in the β and γENaC genes located tandemly on chromosome 16. However, the frequency of sequence variants in patients and control subjects showed no difference between genes.
Conclusions Severe PHA cases are associated with mutations leading to absence of normal‐length α, β or γENaC, while a mild case has been found to be associated with a missense mutation in αENaC. The predominance of PHA‐causing mutations in the αENaC gene may be related to the function of this subunit.
Recently several attempts have been made to introduce molecular karyotyping techniques into prenatal diagnosis. These methods can be used not only for the diagnosis of classical aneuploidies, but ...first of all they should be employed in the diagnostics of microaberrations, which are not revealed by low resolution methods of classical cytogenetics. The new method BACs-on-Beads is designed for quick detection of broad panel of aneuploidies and microdeletions, by the specified detection of deletions and duplications in the examined fetal DNA acquired from amniocytes. Prenatal diagnostics was performed with the use of BACs-on-Beads and classical amniocyte karyotyping simultaneously in a group of 54 pregnancies. This new method proved to be fully compatible with typical karyotyping in cultures of amniocytes in 98.2%. It was confirmed that the main advantage of this method is the possibility of quick diagnosis, within 48 hours, with much wider spectrum of detected anomalies when compared to classical methods. Contrary to other molecular karyotyping methods, the BACs-on-Beads technique is more economical, less time consuming and less complex equipment is needed than in case of other methods. We suppose that this technique can replace classical karyotyping methods in the near future.
Langer-Giedion Syndrome (LGS), with characteristic phenotypic features including craniofacial dysmorphic signs, postnatal growth retardation and skeletal abnormalities, mental impairment, urogenital ...malformations and heart defects, is caused by partial deletions of the long arm of chromosome 8. We present a case of a female fetus with LGS. The diagnosis was molecularly proven with the BACs on Beads method at 32 weeks of gestation. To the best of our knowledge, prenatal recognition of that genetic defect had previously been made in only one case. Also, it has never been described before.
Women who are born with constitutional heterozygous mutations of the BRCA1 gene face greatly increased risks of breast and ovarian cancer. The product of the BRCA1 gene is involved in the repair of ...double-stranded DNA breaks and it is believed that increased susceptibility to DNA breakage contributes to the cancer phenotype. It is hoped therefore that preventive strategies designed to reduce chromosome damage will also reduce the rate of cancer in these women. To test for increased mutagenicity of cells from BRCA1 carriers, the frequency of chromosome breaks was measured in cultured blood lymphocytes following in vitro exposure to bleomycin in female BRCA1 carriers and was compared with noncarrier relatives. The frequency of chromosome breaks was also measured in BRCA1 carriers following oral selenium supplementation. Carriers of BRCA1 mutations showed significantly greater mean frequencies of induced chromosome breaks per cell than did healthy noncarrier relatives (0.58 versus 0.39; P < 10(-4)). The frequency of chromosome breaks was greatly reduced following 1 to 3 months of oral selenium supplementation (mean, 0.63 breaks per cell versus 0.40; P < 10(-10)). The mean level of chromosome breaks in carriers following supplementation was similar to that of the noncarrier controls (0.40 versus 0.39). Oral selenium is a good candidate for chemoprevention in women who carry a mutation in the BRCA1 gene.
Silver-Russell syndrome is heterogeneous both clinically and genetically. The best known genetic aberrations existing in this syndrome are an 11p15 epimutation, present in 20-60% patients, and a ...maternal uniparental chromosome 7 disomy (7-15%) (upd(7)mat). Children with SRS suffer from physical growth impairments - intrauterine and after birth.
The study group consisted of 38 children aged 2 to 17 (x=8.9 ± 4.0 years). These children had undergone a genetic analysis in search for the 11p15 epimutation and the upd(7)mat. Somatic growth was also analysed in terms of birth parameters and postnatal BMI, weight and height. The aforementioned parameters were compared in a subgroup of children with the genetic aberrations and with a control group of children born with IUGR.
In the study group a mean weight SD on birth was -3.41 ± 1.22, the birth height was -1.25 ± 2.08 SD and a head circumference of -3.56 ± 1.93 SD. No significant differences were noted between the SRS study group and the control group in reference to weight and head circumference (p>0.05). Such difference was, however, seen in birth height. Children with 11p15 epimutation had significantly lower weight and height at birth, but a significantly larger head circumference than children without this genetic aberration. When analysing further development of children with SRS, a significantly smaller height SD, body mass and BMI was observed, compared with children from the control group.
Children with SRS present impaired somatic development compared to children with IUGR, and these with a genetic aberration develop worse.
Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data ...showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.
The Aim. Ring chromosome 15 is a very rare genetic abnormality with a wide spectrum of clinical findings. Up to date, about 50 cases have been documented, whereas no reports on ophthalmological ...treatment of such patients have been published. The aim of this study is not only to describe a new patient, but also, for the first time, to present the results of nonoperative management of divergent strabismus. Material and Methods. We present an amblyopic patient with 46,XX, r(15) karyotype: treated conservatively for exotropia of 60 prism diopters. The management consisted of refractive and prismatic correction, eye occlusion, and orthoptic exercises between the age of 15 months and 8 years. Results. The deviation angle of exotropia was decreased to 10 prism diopters, the visual acuity improved to 1.0 in both eyes (Snellen chart) and the fixation pattern was normal. The prisms enabled permanent symmetrical stimulation of the retina, which lead to a development of normal single binocular vision (Maddox test, filter test, and synoptophore tests). Conclusions. Parental karyotype was normal; the analysis of a three-generation pedigree has shown no genetic abnormalities or pregnancy losses so the child’s karyotype anomaly was classified as de novo that is a single occurrence of this type of chromosomal disorder in this family. Strabismus in ring chromosome 15 patients is a difficult condition to manage, although success may be achieved.
PDF
