45,X/47,XY,+ 13 Mosaicism and Crohn's Disease

ABSTRACT. The unusual karyotype 4S,X/47,XY,+13 in an 8.5-year-old girl with the Turner phenotype is described. She displayed none of the phenotypic manifestations of trisomy 13. The patient suffered from Crohn's disease, which is known to be associated with the Turner syndrome. To our knowledge this is the first reported case of Crohn's disease in a patient with 45,X and Y chromosome mosaicism.     

Presence of Turner stigmata in a case of dysgenetic male pseudohermaphroditism with 45,X/46,X+mar karyotype

A case is reported of dysgenetic male pseudohermaphroditism (DMPH) having Turner stigmata and 45,X/46,X+mar karyotype. The marker chromosome of this patient consisted of most if not all of the short arm, including the sex determining region of the Y chromosome. Although this karyotype is relatively common in Turner's syndrome and occasionally observed in mixed gonadal dysgenesis, DMPH is usually exemplified by a 46,XY karyotype except for one patient reported with 45,X/46,XY mosaicism. Turner stigmata have not previously been reported in DMPH. The present patient is an intermediate case between mixed gonodal dysgenesis and typical DMPH, and this indicates that 45,X/ 46,X +mar karyotype abnormality can result in a wide range of phenotype such as DMPH, mixed gonodal dysgenesis and Turner's syndrome.     

Presence of Turner stigmata in a case of dysgenetic male pseudohermaphroditism with 45,X/46,X+mar karyotype

Accepted 19 November 1996
A case is reported of dysgenetic male pseudohermaphroditism (DMPH) having Turner stigmata and 45,X/46,X+mar karyotype. The marker chromosome of this patient consisted of most if not all of the short arm, including the sex determining region of the Y chromosome. Although this karyotype is relatively common in Turner''s syndrome and occasionally observed in mixed gonadal dysgenesis, DMPH is usually exemplified by a 46,XY karyotype except for one patient reported with 45,X/46,XY mosaicism. Turner stigmata have not previously been reported in DMPH. The present patient is an intermediate case between mixed gonodal dysgenesis and typical DMPH, and this indicates that 45,X/46,X+mar karyotype abnormality can result in a wide range of phenotype such as DMPH, mixed gonodal dysgenesis and Turner''s syndrome.

     

Turner Syndrome with Ulcerative Colitis

Turner syndrome is a chromosomal disease frequently associated with autoimmune disorders including diabetes mellitus, thyroid disease and inflammatory bowel disease (IBD). Although the etiology of IBD has not been fully elucidated, genetic analysis has recently revealed several susceptibility genes. Recently, cases with Turner syndrome associated with IBD have been reported. We report here a 13-yr-old girl with Turner syndrome associated with ulcerative colitis. The patient was undergoing growth hormone treatment and presented with abdominal discomfort and bloody diarrhea. Her karyotype pattern was 46,X,i(Xq). Barium enema revealed punctate collections of barium suggesting microulcerations in the descending and sigmoid colon with loss of haustra. Flexible sigmoidoscopy showed that the mucosa was erythematous and friable upon touch and that the wall had frank hemorrhage and inflammatory polyp formation from the anal verge through the splenic flexure. Histologically, mucosal and submucosal inflammation was prominent, suggesting cryptitis and crypt abscess formation. Based on these findings, she was diagnosed as having ulcerative colitis, and 5-aminosalicylic acid, prednisolone and dietary therapy were initiated. Our observations in this patient suggest that X chromosome abnormality may influence the development of IBD and that screening for gastrointestinal disease in patients with Turner syndrome may help lengthen life expectancy in these patients.     

Low stature in males with normal phenotype and 45,X/46,XY mosaicism

There is wide variation in the clinical expression of 45,X/46,XY mosaicism. Ninety percent of prenatally diagnosed boys have normal male phenotype at birth, while those diagnosed postnatally show a wide spectrum of phenotypes, ranging from Turner syndrome, mixed gonadal dysgenesis, and male pseudohermaphroditism to apparent normality. We report the clinical, cytogenetic, endocrinologic and histologic findings in three boys with an apparently normal male phenotype and 45,X/46,XY mosaicism who were diagnosed postnatally because of their short stature. With the exception of one patient with Turner stigmata, no other abnormal features were found. No correlation between the proportion of 45,X/46,XY cell lines in blood, gonads and phenotype was found. Both prenatally and postnatally diagnosed boys with normal male phenotype must be followed-up because they can develop late-onset abnormalities, such as dysgenetic testes leading to infertility or neoplastic transformation, and short stature, which could be improved with growth hormone therapy.     

Y Chromosome Specific DNA Probe in the Diagnosis of a Patient with mos 45, X/46, XYnf

In a patient with mos 45,X/46,XYnf, the diagnosis was confirmed with a Y chromosome-specific DNA probe, Y-190. The patient was a phenotypic female without Turner syndrome stigmata other than short stature. She showed some evidence of virilization and high serum testosterone. Her peripheral blood karyotype was mos 45,X/46X, +mar. Although this marker chromosome resembled a Y chromosome, there was no quinacrine bright region on its long arm. Southern blot analysis of her peripheral blood mononuclear cell DNA with Y-190 as a probe showed strong hybridization with this probe. Gonadectomy was performed, and bilateral gonadoblastomas were found.     

A 13-year-old female with Turner syndrome and achalasia

The most common gastrointestinal problems associated with Turner syndrome are intestinal telangiectasia, colon carcinomas, inflammatory bowel, and liver diseases. In this paper we present for the first time a 13-year-old female with 45,X karyotype associated with achalasia. As far as we know, achalasia associated with Turner syndrome has not been reported previously. The aim of this report was to point out the association of Turner syndrome and achalasia. It could be a coincidental or Turner syndrome-associated finding.     

Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study

A 13-year-old phenotypically female patient presented with short stature (height SDS –2.6), but without any Turner stigmata or other dysmorphic features. Chromosome analysis showed mosaicism for an isodicentric (idic) (Y)(q11.23) containing cell line and a 45,X cell line. Subsequent gonadectomy revealed a left streak ovary and a right ovary of abnormal appearance, which on histological examination appeared to contain a gonadoblastoma. DNA analysis showed that the proposed critical region of the gonadoblastoma locus on the Y chromosome was contained within the patient's idic (Y). Conclusion The case described here shows that patients with 45,X/46,X, isodicentric (Yp) mosaicism and a female phenotype (1) can lack external virilisation but still have a gonadoblastoma and (2) do not necessarily have Turner stigmata but can present with only short stature. This case also underlines the importance of karyotyping patients with unexplained short stature to enable gonadectomy if Y-derived material is detected. Received: 12 July 2000 / Accepted: 20 September 2000     

Clinical and gonadal features and early surgical management of 45,X/46,XY and 45,X/47,XYY chromosomal mosaicism presenting with genital anomalies

ObjectiveThe 45,X/46,XY and 45,X/47,XYY group of patients includes some of those previously diagnosed with ‘mixed gonadal dysgenesis’. Our aim was to establish the clinical and gonadal spectrum, and early surgical management, of patients with chromosomal mosaicism presenting with genital anomalies.Patients and methodsWe performed a retrospective review of patients with 45,X/46,XY or 45,X/47,XYY mosaicism presenting with genital ambiguity between 1988 and 2009. At least one gonadal biopsy or gonadectomy specimen was available for each patient. Gonadal histology was re-evaluated by a paediatric pathologist.ResultsOf 31 patients with 45,X/46,XY (n = 28) or 45,X/47,XYY (n = 3) mosaicism and genital anomalies, 19 (61%) were raised male. Histology of 46 gonads was available from patients who had undergone a gonadectomy or gonadal biopsy, at a median age of 9.5 months. 18 gonads were palpable at presentation, including 5 (28%) histologically unremarkable testes, 2 streak gonads, and 1 dysgenetic gonad with distinct areas of testicular and ovarian stroma but no oocytes. All intra-abdominal gonads were found to be dysgenetic testes (of which 2 were noted to have pre-malignant changes) or streaks, apart from 1 histologically unremarkable testis. 15 (48%) patients had other anomalies, most commonly cardiac and renal; 4 (13%) had a Turner phenotype.ConclusionThe anatomy and gonadal histology of 45,X/46,XY and 45,X/47,XYY individuals with genital ambiguity do not conform to a set pattern, and hence management of each patient should be individualized according to detailed anatomical and histological assessment.     

45,X Turner综合征合并中枢性性早熟1例报告并文献复习

目的总结Turner综合征(TS)合并中枢性性早熟的诊断和治疗经验,提高对该病的认识。方法报道1例45,X TS合并中枢性性早熟诊断、治疗和随访病例,对相关文献进行复习。结果患儿,女,7.5岁,因"乳房增大半年"就诊。身高117.9 cm(P_(7.2)),体重32.5 kg,肥胖外观,无高腭弓、颈蹼、盾形胸和肘外翻,乳房Tanner分期Ⅱ期,心肺查体未见异常,外阴阴毛Tanner分期Ⅰ期。辅助检查:促性腺激素释放激素(LHRH)激发试验峰值:黄体生成素(LH)11.9 U·L~(-1),卵泡刺激素(FSH)34.2 U·L~(-1),雌二醇(E2)39.3 ng·L~(-1)。盆腔超声示卵巢增大。骨龄9.7岁。应用促性腺激素释放激素类似物(GnRHa)治疗2.7年后,身高131.4 cm,骨龄12岁,联合重组人生长激素(rh GH)继续治疗2.3年,身高148.4 cm,骨龄13岁。停药1年半后身高154.2 cm,接近遗传靶身高,检测LH 11.9 U·L~(-1),FSH 50.5 U·L~(-1),E2 38.9ng·L~(-1),染色体:45,X。系统文献检索国外仅有6例TS合并中枢性性早熟的病例报告,其中5例染色体为嵌合体,1例为1条X染色体的片段缺失。结论单体型TS可出现中枢性性早熟,GnRHa联合rh GH治疗能够改善患儿成年终身高。     

Neugeborener Junge mit Ullrich-Turner-Syndrom?

We present a newborn whose prenatal chromosomal analysis had shown a Turner syndrome with genotype 45,X. However, a male phenotype with glandular hypospadias and normal gonadal development was present. Chromosomal analysis was repeated postnatally, which then presented a mosaic that can underlie a mixed gonadal dysgenesis: 45,X[80%]/46,X,idic(Y)(p11.32)[20%]. Further molecular cytogenetic analyses and possible impacts on the patient’s development are discussed.     

Normal growth and normalization of hypergonadotropic hypogonadism in atypical Turner syndrome (45,X/46,XX/47,XXX)

A comparison has been made of a case with 45,X/46,XX/47,XXX mosaicism with some 50 cases in the literature. A significant positive correlation was found between height standard deviation scores of mosaic patients from the literature and the frequency of cells with a normal chromosome constitution (n=21,r _s =0.552,P<0.01). In contrast, a significant negative correlation was seen between body height and the frequency of cells with a 45,X constitution (n=21,r _s =–0.594,P<0.01). There was no significant correlation of height standard deviation score with the 47,XXX cell line (n=21,r _s =–0.353). A patient with a rare chromosomal mosaicism (45,X/46,XX/47,XXX) is described. The diagnosis was first made by chromosome analysis in amniotic cells. The patient showed no symptoms suggestive of Turner syndrome and growth followed the 75th height percentile. Basal and gonadotropin-releasing hormone stimulated gonadotropin levels normalized after age 4.8 years and did not subsequently return to hypergonadotropic levels. In blood lymphocytes, there was an increase in the frequency of cells with a normal chromosome constitution over 9 years. This in vivo cell selection is discussed. Chromosome analysis in skin fibroblasts showed the same triple mosaicism with a similar distribution of cell lines as in blood lymphocytes. In conclusion, statistical evidence was demonstrated that the severity of short stature is correlated with the distribution of cell lines in 45,X/46,XX/47,XXX mosaicism. This finding is of importance for the genetic counselling in cases of prenatal diagnosis of mosaic Turner syndrome.     

45,X/46,XX mosaicism in turner’s syndrome

Summary A short-statured phenotypic female with primary amenorrhoea, infantilism, shield chest and 9% sex chromatin bodies in buccal smears had 2 cell lines, 45/46, in cultured leucocytes. She was diagnosed as a case of Turner's syndrome with X/XX chromosomal mosaicism. This patient is another example of modification of the Turner phenotype by the presence of a normal XX cell line. The report highlights the importance of cytogenetic investigations in short-statured females who do not possess all the clinical features of the classical form of Turner’s syndrome. From the Chaudhuri Centre for Medical Genetics, Calcutta-14.     

Coarctation of the aorta in Turner syndrome: a pathologic study of fetuses with nuchal cystic hygromas, hydrops fetalis, and female genitalia

Congenital heart disease is a frequent feature of Turner syndrome. Although the most frequent cardiac lesion is coarctation of the aorta, a spectrum of cardiac defects occurs which is limited almost exclusively to defects associated with decreased blood flow through the left heart. We report the results of gross anatomic and microscopic dissection of 12 fetuses aborted between 16 and 26 weeks' gestation, with the classic Turner phenotype of nuchal cystic hygromas, hydrops fetalis, and female genitalia. Eight fetuses showed a consistent constellation of cardiac defects: diminution of the ascending aorta, large pulmonary artery ranging from 1 1/2 to three times the size of the aorta, large patent ductus arteriosus, and juxtaductal coarctation. Another fetus had hypoplastic left heart and aortic atresia. The remaining three fetuses had normal cardiac anatomy. The lymphatic vessels at the base of the great vessels were carefully examined in nine of the fetuses. Although there was no definite correlation between the degree of cardiac pathology and the extent of lymphatic aberrations at the base of the heart at the time of postmortem examination, the high incidence (75%) of left-sided flow defects among these fetuses, all of whom had large hygromas and severe edema, supports the hypothesis that there is a pathogenetic relationship between lymphatic obstruction and congenital heart disease in the 45,X Turner fetus.     

t(6;9)(p23;q34) presenting acute myeloid leukemia in a child with an unsuspected 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution: yet another Y chromosome overdosage and malignancy association

Development of leukemia in patients with sexual chromosome abnormalities is relatively rare and mostly involves cases of monosomy X, Turner syndrome. Here, we report on a child having a 45,X/46,X,derY [?t(Yp;Yq)] chromosomal constitution (variant Turner syndrome) presenting with concordant acute myeloid leukemia and a rarely seen clonal neoplasic cell lineage-related karyotype, t(6;9)(p23;q34).     

Quality of life in Turner syndrome is related to chromosomal constitution: implications for genetic counselling and management

Skuse D, Elgar K, Morris E. Quality of life in Turner syndrome is related to chromosomal constitution: implications for genetic counselling and management. Acta Pædiatr 1999; Suppl 428: 110–13. Stockholm. ISSN 0803–5326
Issues of self-appraisal, friendships and academic attainments are uniquely salient for all adolescents. For girls with Turner syndrome, social problems and learning difficulties often become more serious at this time, yet may be unacknowledged by those responsible for Pædiatric care because their focus is on growth and sexual maturation. Data on the social and educational adjustment of 110 45,X (monosomic) females aged between 6 and 25 years is presented. Detailed information on the patients'precise karyotype was used to demonstrate systematic differences in adjustment between those whose single X chromosome was maternally derived and those in whom it was paternal. Implications for educational support and parental guidance are discussed. □ Educational attainments, karyotype, non-verbal intelligence, quality of life, social adjustment, Turner syndrome, verbal intelligence     

A clinical and cytogenetic study of 50 women with Turner's syndrome. Considerations of the problem of pregnancies in these patients. Part 2

The results of a study on 50 patients with Turner syndrome, all of them older than 14 years and never treated, are reported. In order to correlate karyotypes and clinical manifestations of the syndrome, we performed a complete physical examination and ultra sonographic tests of the heart, kidneys, uterus and ovaries. We found a better spontaneous growth and sexual maturation in mosaic 45.X/46.XX patients than in patients with 45.X and X structural anomalies. No differences were found in heart and kidney congenital anomalies between groups of patients with different karyotypes. We conclude that the presence of an XX-line has an ameliorating effect on height and gonadal function of patients with Turner syndrome.     

Abdominal ultrasound in Noonan syndrome: A study of 44 patients

Noonan syndrome affects approximately 1 in 1500 live births. Affected individuals may have characteristic phenotypic features some of which are shared with Turner syndrome, although in Noonan syndrome the karyotype is normal, unlike the 45X karyotype of Turner syndrome. Renal anomalies have been described in both syndromes and in Turner syndrome they are both common and frequently severe. The frequency and spectrum of renal anomalies in Noonan syndrome have not been well documented. Upper abdominal ultrasound was performed to establish the frequency of renal anomalies in Noonan syndrome. Forty-four individuals with Noonan syndrome, aged between 9 months and 38 years, were studied. Sixteen scans (36%) were normal and 28 (64%) were abnormal. Five patients (11%) had renal anomalies. Twenty-three patients (53%) had splenomegaly, 6 of these with associated hepatomegaly. One patient had a choledochal cyst and a midgut malrotation. The frequency of renal anomalies in Noonan syndrome is 11%, which is lower than that seen in Turner syndrome. However, splenomegaly with or without hepatomegaly occurs commonly. Choledochal cyst and solitary kidney, previously unreported in Noonan syndrome, are documented.     

The clinical and genetic heterogeneity of mixed gonadal dysgenesis: does “disorders of sexual development (DSD)” classification based on new Chicago consensus cover all sex chromosome DSD?

Clinical findings illustrate the wide spectrum of the phenotypic manifestations of 45,X/46,XY mosaicism in the sex chromosome disorders of sex differentiation (DSD). The objective of study is to evaluate the characteristics of 45,X/46,XY patients and questioning of their place within the DSD categorization. The clinical findings of 11 patients with 45,X/46,XY mosaicism are described including the presentation, gonadal morphology, genital anatomy, and the hormone levels among 285 patients with DSD evaluated. Sixty-seven patients were diagnosed with sex chromosome DSD (50 Turner, three Klinefelter, ten 45,X/46,XY gonadal disgenesis, one 45X/46,XY ovotesticular DSD, one 47,XYY ovotesticular DSD, and two 46,XX/46,XY ovotesticular DSD). The type and the percentage of patients with 45,X/46,XY mosaicism were as follows: Four cases of mix gonadal dysgenesis, four cases of partial gonadal dysgenesis, two cases of complete gonadal dysgenesis, one case of ovotesticular DSD. On the other hand, another patient that has 45,X/46,XX mosaicism was diagnosed with MGD with the presence of the streak gonad on the right side and the testis on the other side. Conclusion: We suggest that sex chromosome DSD categorization can include 45,X/46,XY PGD and 45,X/46,XY CGD. Mixed gonadal dysgenesis may be also placed among the disorders of testicular differentiation of 46,XY DSD subdivision.     

A 45 X/46 X dic (Yq) puberal male without genital ambiguity. Critical study of the peculiarities of his phenotype]

A boy with a chromosomal mosaic 45 X/46 X dic Yq is described. The unusual features were a Turner phenotype with normal genitalia and he was in puberty. It is apparent that it is not possible to blame alterations in the Y chromosome when this mosaic is associated with ambiguous genitalia or the stigmata of Turner's syndrome.