Turner syndrome: the Leuven experience (1965-1989) in 478 patients. I. Patient's age at the time of diagnosis in relation to chromosomal findings

Within the past 25 years 478 patients with Turner syndrome have been diagnosed in the Leuven Centre for Human Genetics. After exclusion of 36 lost pregnancies, mostly first trimester spontaneous abortions, almost 20 per cent of the remaining 442 Turner syndrome patients have been early detected, i.e. before the age of two years. Moreover, a high prevalence of classic 45,X karyotype over other karyotypes was observed in this age group. The high mortality of prenatally diagnosed Turner syndrome fetuses is discussed here in view of the most common associated congenital malformations.     

Psychosocial functioning, self-perception and body image and their auxologic correlates in growth hormone and oestrogen-treated young adult women with Turner syndrome

BACKGROUND: Few data are available on the psychosocial status of growth hormone (GH) and oestrogen treated women with Turner syndrome (TS). In this study, we evaluated psychosocial functioning, self-concept and body image in GH and oestrogen treated young adult women with TS and we studied the relationship with auxological parameters. PATIENTS AND METHODS: Thirty women with TS (mean +/- SD age: 22.1 +/- 2.4 years), all treated with GH and oestrogens if indicated, and an age-matched reference group of 44 non-Turner female students (age: 20.5 +/- 2.1 years) completed 3 questionnaires evaluating, respectively, behavioural and emotional problems (Young Adult Self Report), self-concept (Self Perception Profile for College Students) and body-image (Body Attitude Scale). RESULTS: TS patients did not report more behavioural and emotional problems compared to the non-TS females except for attention problems; they even reported fewer problems on some subscales (somatic complaints, thought problems, delinquent behaviour). TS patients did not differ from the non-TS female group in their bodily satisfaction. TS patients, particularly patients with a 45,X karyotype, perceived themselves as less socially competent. BMI was significantly related to the appraisal score of the Body Attitude Scale, whereas height was not related to any of the evaluated psychosocial parameters. CONCLUSION: The psychosocial adaptation of young adult women with TS, diagnosed at an early age and treated during childhood with GH and oestrogens if indicated, appears to be quite satisfactory. Follow-up of adult TS patients should not neglect the problem of overweight and associated psychosocial consequences.     

The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females

Turner syndrome females (45,X) do not have mental retardation (MR), whereas some mosaic ring X Turner syndrome females, with 45,X/46,X,r(X), have severe MR. The MR is believed to be caused by a failure of X chromosome inactivation (XCI) of the small ring X chromosome, which leads to functional X disomy (FXD), To explore this hypothesis, we examined the proportion of FXD cells in the peripheral blood of four ring X Turner syndrome females with various levels of MR, using two newly developed XCI assays based on DNA methylation of X-linked genes. As a result, the two patients with extremely severe MR showed complete FXD patterns, whereas the remaining two patients with relatively milder MR showed partial FXD patterns. These results indicate that the proportion of FXD cells may be associated with the severity of MR in mosaic ring X Turner syndrome females, although this association should be confirmed by examining brain cells during development. One of the cases with severe MR and a complete FXD pattern neither lacked the XIST gene nor had uniparental X isodisomy, and we discuss the mechanism of the failure of XCI in this case.     

High incidence of mental retardation in Turner syndrome patients with ring chromosome X formation

In this report we describe and comment the high incidence of mental subnormality in a series of 21 Turner syndrome patients with ring chromosome X, diagnosed in Leuven in the period 1965-1989. In 7 of the 21 (one third) a varying degree of mental retardation, from borderline intelligence to severe mental retardation was found. In 4 of them (18.5%) mental retardation was moderate to severe.     

Portal vein thrombosis and high factor VIII in Turner syndrome

BACKGROUNDS/AIMS: Turner syndrome is not usually associated with thrombotic events. The aim of this study is to report 3 Turner syndrome patients with portal vein thrombosis and, in 2 of them, high factor VIII. These findings are compared to values in Turner syndrome patients without thrombosis and controls. METHODS: In different years, 3 patients with Turner syndrome were initially seen at the Gastroenterology Clinic of Hospital de Clínicas de Porto Alegre, Brazil, for portal vein thrombosis. After the most common causes of portal vein thrombosis and thrombophilias had been excluded, the 2 surviving patients were studied for clotting factors VIII, IX and von Willebrand factor. The same factors were also assessed in 25 Turner syndrome patients without thrombosis and 25 normal girls. RESULTS: One of the patients with portal vein thrombosis died before the study. In the 2 surviving patients, factors VIII and von Willebrand levels were >150 IU/dl, which is considered to be high. In Turner syndrome patients without thrombosis, the mean factor VIII level was 127.2 +/- 41.1 IU/dl and for von Willebrand factor 101.2 +/- 26.9 IU/dl, while in control girls these were 116.0 +/- 27.6 and 94.28 +/- 27.5 IU/dl, respectively. Factor VIII and von Willebrand factor were not different between these 2 groups. When non-O blood group Turner syndrome patients and normal girls were compared, the former had significantly higher levels of factor VIII. CONCLUSIONS: This is the first report on the unusual finding of portal thrombosis in patients with Turner syndrome in whom high levels of factor VIII and von Willebrand factor were found. Factor VIII is higher in the non-O blood group Turner syndrome patients without thrombosis when compared to normal girls.     

Plastic Repair Following the Removal of Large Desmoid Tumors of the Abdominal Wall

The case records of 100 patients over the age of 60 at the time of their admission to a state mental hospital in California were evaluated, using rigid criteria to determine whether the precipitating cause for their state hospitalization was due to a deterioration of their mental state or a change in their socio-environmental milieu. The results of the study indicated that 77 per cent of these patients were in hospital because of a deterioration in their own mental state while 23 per cent were there because of a deterioration in their socio-environmental milieu. The data also were indicative that the proportion of patients put in hospital because of a deterioration in their socio-environmental milieu might conceivably be higher than 23 per cent if subtle changes in family attitude towards the patient could be adequately evaluated.     

Radiological signs of Leri-Weill dyschondrosteosis in Turner syndrome

BACKGROUND/AIMS: Leri-Weill dyschondrosteosis (LWD), a mesomelic short stature syndrome with Madelung deformity, was recently reported to be caused by SHOX (short stature homeobox-containing gene) haploinsufficiency. The loss of SHOX on Xp22.32, also called PHOG (pseudoautosomal homeobox-containing osteogenic gene), through structural aberrations of the X chromosome was also implicated in the short stature phenotype and some additional stigmata of Turner syndrome. The aim of this study was to systematically examine left-hand radiographs from Turner girls for the presence of signs of LWD. METHODS: We retrospectively studied 168 left-hand radiographs from 54 patients with Turner syndrome (bone age >10.5 years) who were treated with rhGH and seen during the last 10 years in our clinic. For comparison, we analyzed 7 radiographs from 5 patients with LWD and 52 radiographs from 20 patients with GH deficiency. The shape of the distal radial epiphysis (triangularisation index = TI) and the carpal angle were quantitatively measured. In addition, we screened for the presence of a premature cleft fusion or an ulnar deviation of the articular surface of the distal radial epiphysis and for fourth metacarpal shortening. One of 54 Turner girls (2%) was affected with LWD and presented with Madelung deformity. RESULTS: No milder forms of Madelung deformity were detected. However, there was a significant trend to a triangular shape of the distal radial epiphysis in Turner syndrome: the median TI was 2.7 in normal controls (range 1.8-3.7), 3.1 in Turner girls (range 2.0-6.3) (p < 0.001 against controls), and 6.0 in patients with LWD (range 3.5-11.0) (p < 0.001 against controls). CONCLUSIONS: The triangularisation index did not correlate with the carpal angle (median 122.5 Copyright 2001 S. Karger AG, Basel     

Psychosocial functioning after discontinuation of long-term growth hormone treatment in girls with Turner syndrome

It is common practice in the case of Turner syndrome (TS) to treat short stature with GH treatment and to induce puberty with estrogens at an age as close to normal puberty as possible. This approach in most cases leads to a height in the normal range in childhood, adolescence, and adulthood in TS. Little data is available, however, on its effect on psychosocial functioning. In the present study, we evaluated psychosocial functioning in a group of 50 women with TS, after reaching final height in two multicenter GH trials. Thirty-six girls participated in a randomized dose-response study from mean (SEM) age 6.8 (0.4) years, and 14 girls participated in a frequency-response study from age 13.2 (0.4) years. After discontinuation of long-term GH treatment, these 50 girls were evaluated for psychosocial functioning at a mean age of 18.8 (0.3) years. GH was given in a dosage of 4 IU/m2/day (approximately 0.045 mg/kg/day), 6 IU/m2/day, or 8 IU/m2/day. After a mean GH treatment duration of 7.1 (0.4) years, mean final height (ref. normal girls) was FH1.2 (0.2) SD score. Behavioral problem scores (Achenbach) of the TS women were comparable to normal Dutch peers. Although self-perception (Harter total scale: p < 0.01), and bodily attitude (Baardman: p < 0.05) was significantly less positive than for their normal Dutch peers, we found no evidence of depression. TS women rated their family functioning higher than their Dutch peers (p < 0.0001), and had a slightly different coping pattern. These results show that even after reaching a height in most cases within the normal range and puberty induction at a pubertal age, some women with TS still experience psychosocial problems. It is likely, however, that GH and estrogen treatment improved psychosocial functioning. Long-term follow-up of these GH-treated patients will allow an evaluation of their life achievements.     

Low areal bone mineral density values in adolescents and young adult turner syndrome patients increase after long-term transdermal estradiol therapy

OBJECTIVE: To study the effects of long-term estradiol therapy on areal bone mineral density (aBMD) values in young adult Turner syndrome patients. METHODS: The effects of 2-year transdermal estradiol administration on lumbar, L2-L4, aBMD values were evaluated in 12 Turner syndrome patients, 15.41-21.85 years old, who had reached adult height and had low aBMD values. Puberty was induced in all at a chronological age above 12 years and menarche appeared between 13.82 and 15.40 years. The patients were on oral estrogen/gestagen therapy from then until the start of the study. Adhesive patches of 17-beta-estradiol designed to be worn for 72 h and deliver 100 microg of estradiol per day, which results in a steady mean serum estradiol level of 75 pg/ml, were used for 21 days. From day 11 to day 21, 10 mg of oral didrogesterone were also added. Nutritional and physical activity habits were evaluated at the beginning, after 1 year and at the end of the study. RESULTS: aBMD values significantly increased from 0.910 +/- 0.065 to 1.005 +/- 0.086 g/cm2 (10.06 +/- 3.37%) and the z-score from -2.38 +/- 0.63 to -1.54 +/- 0.71 (0.81 +/- 0.30 z-score). No significant differences were observed in body mass index, calcium intake and physical activity habits at the start, during and at the end of the study. CONCLUSION: In summary, our results underline the importance of estrogens for bone mass peaking and suggest that this therapeutic protocol may be useful in the therapy of Turner syndrome patients with low bone mass.     

Dermatoglyphics in turner syndrome

Finger and Palmar dermatoglyphics in 25 karyotypically proven cases of Turner syndrome representing Northwestern region of India are presented and compared with those obtained on their 102 normal female counterparts. Predominance of ulnar loops over other patterns was recorded in turner patients. Mean total finger ridge count in Turner syndrome (147.4) remained higher than the normal females (121.1). c-d interdigital ridge count in turners remained significantly (p≤0.05) higher than their normal female counter-parts. In contrast to their western counterparts distal placement of axial triradius in both the palms of none of the Turner syndrome patients representing the current series was recorded. Occurrence of whorls and arches in hypothenar region of 12% and 4% was respectively noticed in right palm of patients. The use of distinctive dermatoglyphic features recorded amongst Turner syndrome patients representing this study may be made to corroborate diagnosis of this entity in settings where facilities to carry out karyotyping do not exist.     

Mental health in situations of armed conflict

Mental health is a serious problem in Latin America where many communities have been directly affected by armed conflict, communities in which large population groups have been displaced or have sought refuge. Research studies and epidemiological statistics are summarized to emphasize the psychosocial consequences of traumatic events associated with armed conflict. In addition to specific psychological disorders, other more generalized are considered such as fear, affliction, diseases, social disorder, violence and psychoactive substance consumption. Finally, the main points of a mental health plan for emergency situations are described which include the following: (1) preliminary diagnosis, (2) increase, decentralize and strengthen mental health public services, (3) psychosocial attention to the prevailing disorders--with emphasis on childhood problems, (4) initiate training and use of non-specialized personnel, and (5) identification of special needs requiring attention by psychologists and psychiatrists. Other aspects emphasized were community education, training, social communication, community organization, social participation, interinstitutional coordination, flexibility, sustainability, and specific actions in accordance with local needs.     

The various phenotypes in Xp deletion. Observations in eleven patients

Summary Eleven Xp-deletion patients with various phenotypes ranging from normal to the Turner syndrome are reported. To explain the phenotypy-karyotype correlation the hypothesis is brought forward that (an) autosomal gene(s) may play a role in the pathogenesis of the Turner syndrome.     

Chromosomal abnormalities associated with mental retardation in female subjects

Chromosomal abnormalities are thought to be the most common cause of mental retardation (MR). However, apart from a few selected types with typical aneuploidy, like Downs syndrome, Klinefelter syndrome, Turner syndrome, etc., the frequency of detectable chromosomal abnormalities in association with idiopathic MR is very low. In this study, we have investigated chromosomal abnormalities in female MR subjects (n = 150) by high-resolution GTG banding. Of them, 30 cases were diagnosed as Downs syndrome. Among the remaining (n = 120), chromosomal abnormalities/marked polymorphisms were detectable in only three MR cases (0.025).     

Transition-Related Discussions Among Adolescent Females With Turner Syndrome: Current Practices and Associated Factors

ObjectiveTo examine the current transition practices and factors associated with the occurrence and timing of transition-related discussions among adolescents with Turner syndrome (TS).MethodsA retrospective chart review was conducted at a large pediatric academic center among females with TS seen between 12 and 25 years of age. Medical/developmental characteristics, the age at transition, documented transition-related discussions, and the utilization of transition readiness assessment tools were abstracted. Analyses were conducted to examine the age/occurrence of discussions and associated factors.ResultsRecords of 112 patients were reviewed. The average age of TS diagnosis was 7.6 ± 5.8 years, and the average age of those that transitioned from pediatric to adult care (n = 21) was 20.1 ± 2.0 years. Only 22% of individuals had documented discussions regarding transition to adult care, and no transition readiness tools were utilized. The majority of transition-related discussions began between 11 and 15 years. Estrogen and cardiovascular counseling were common (84% and 75%, respectively). Less than half of the subjects had reproductive (40%), lifestyle (43%), and psychosocial (12%) discussions. Cardiovascular conditions were associated with transition to adult care discussions, and neurodevelopmental conditions were associated with psychosocial counseling. In those that transitioned to adult care, transition-related discussions occurred in only half of patients.ConclusionOur findings emphasize the need for the development and implementation of a standardized transition process for adolescents with TS, with particular attention to transition to adult care and reproductive, lifestyle, and psychosocial counseling. The utilization of formal transition tools may also help prepare these girls for transition to adult care.     

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1.

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.     

Gender-specific differences of serum leptin in obese and normal-weight adolescents: studies in type-I diabetes and Turner syndrome

The influence of exogenous insulin and estrogen substitution on serum leptin-like immunoreactivity was studied longitudinally in patients with type-I diabetes and Turner syndrome using a specific radioimmunoassay. Prepubertal, pubertal and postpubertal samples of 17 patients (9 girls, 8 boys) with type-I diabetes mellitus developing obesity were compared to those of 17 normal-weight controls matched for gender, age and diabetes duration. Six obese and six normal-weight girls with Turner syndrome were studied without hormone substitution, with ethinylestradiol alone, and with cyclic estradiol/gestagen substitution. The mean leptin levels of the girls with diabetes were two times higher than boys at all times, while insulin doses and glycemic control had no influence. In Turner syndrome estrogen substitution led to increased leptin levels only in the obese group. This study revealed that both body weight above normal and female sex steroids seem to be necessary to elevate leptin concentrations, while exogenous insulin has no effect.     

Molecular detection of XO - Turner syndrome

Turner syndrome is caused by haploinsufficiency of the short arm of X-chromosome, and is usually diagnosed by karyotyping. This procedure is time-consuming, expensive and unfeasible for population screening. We propose molecular detection of 45XO Turner patients based on the ability of HpaII, a methylation sensitive endonuclease, to induce the cleavage of non-methylated DNA in the active X-allele. Genomic DNA was obtained from 22 patients with Turner syndrome confirmed by karyotype (45XO, N = 18; 45XO/46XX, N = 4). After digestion, DNA was amplified with primers directed to exon 1 of the androgen receptor (AR) gene and to the GAPDH control gene. Normal control females or mosaic patients, with a second methylated X-chromosome, escaped from HpaII digestion and produced a band corresponding to AR gene amplification. 45XO patients have just one active non-methylated X-chromosome, completely digested by HpaII, thus preventing the amplification of the AR gene. Three of the 45XO cases gave amplified bands, suggesting low-frequency mosaicisms that are not detected by karyotyping. Compared to classical karyotype studies for the detection of 45XO Turner patients, this new molecular method is simpler, faster and less expensive.     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

Family history interview of a broad phenotype in specific language impairment and matched controls

The aim was to study a broader phenotype of language‐related diagnoses and problems in three generations of relatives of children with specific language impairment (SLI). Our study is based on a family history interview of the parents of 59 children with SLI and of 100 matched control children, exploring the prevalence of problems related to language, reading, attention, school achievement and social communication as well as diagnoses such as attention‐deficit hyperactivity disorder (ADHD), autism, Asperger syndrome, dyslexia, mental retardation, cleft palate and stuttering. The results show a spectrum of language‐related problems in families of SLI children. In all three generations of SLI relatives, we found significantly higher prevalence rates of language, literacy and social communication problems. The risk of one or both parents having language‐related diagnoses or problems was approximately six times higher for the children with SLI (85%) than for the control children (13%) (odds ratio = 37.2). We did not find a significantly higher prevalence of the diagnoses ADHD, autism or Asperger syndrome in the relatives of the children with SLI. However, significantly more parents of the children with SLI had problems with attention/hyperactivity when compared with the parents of controls. Our findings suggest common underlying mechanisms for problems with language, literacy and social communication, and possibly also for attention/hyperactivity symptoms.