Fragile-X syndrome III: dermatoglyphic studies in males

Dermatoglyphics of 39 males with the fragile-X syndrome were compared with those of 3 groups of control subjects; 497 school boys, 15 males with non-specific mental retardation, and 15 with Down syndrome. Compared with the control males, there was an increased frequency of radial loops, whorls, and arches on the fingers and of third interdigital patterns and abnormal creases on the hands, and a decreased frequency of ulnar loops and fourth interdigital patterns in the patients with the fragile-X syndrome. The mean a-b ridge count was lower than in controls and there were more patients than controls with an a-b ridge count less than 70. All of these differences were significant at p less than 0.01. There was no differences between patients and controls with respect to total ridge count on the fingers and the dermatoglyphics in other areas of the hands or feet. From this small study a preliminary index was developed that attempts to distinguish male patients with the fragile-X syndrome from normal male controls and males with non-fragile-X forms of mental retardation. The patterns on the left and right third fingers, the a-b ridge count, and the palmar creases were used in the index. Sixty-four % of patients with the fragile-X syndrome would be selected out if greater than or equal to + 0.5 was used as the criterion and 90% of these males would be expected to have the fragile-X chromosome.     

Screening for fra(x) mutation and Klinefelter syndrome in mental institutions

A total of 9153 male subjects in mental institutions from six different Italian districts were screened for the presence of bilateral microorchidism, in order to detect Klinefelter syndrome. Among the 212 microorchidic patients found, 33 had an XXY karyotype (15.5%). Ninety-one Klinefelter patients with normal intelligence were also examined as a control group. Cytogenetical and clinical findings were compared in these two groups of patients and no difference was found. Two fra(x)positive subjects were found, one for each group of XXY patients; the influence of fra(x) mutation on their phenotype is discussed.     

Trisomy Xq in a male: the isochromosome X Klinefelter syndrome

We report on a male with trisomy Xq resulting from an isochromosome Xq which is preferentially inactivated: 47,XY,+i(Xq). Six previous cases have been reported. These patients are similar to patients with classical Klinefelter syndrome (47,XXY) in that they have infertility, decreased masculinization, gynecomastia, and elevated luteinizing hormone (LH) and follide stimulating hormone (FSH) levels. They may differ in having average intelligence and normal to short stature. These findings indicate that extra copies of the long arm of X have phenotypic expression, even though activated only in early development.     

The concurrence of Klinefelter syndrome and fragile X syndrome

In this paper we report on a third patient with Klinefelter syndrome and fragile X. In the Leuven experience the simultaneous occurrence of both conditions is 1:155 (3 fra(X) positive Klinefelter patients in a total number of 465 fra(X) positive males), a concurrence much higher than expected by chance considering the frequency of both conditions.     

Klinefelter syndrome and mediastinal germ cell tumors

Precocious puberty is not a typical manifestation of patients with Klinefelter syndrome (KS). However, there is an increased incidence of mediastinal germ cell tumors (M-GCT) in KS, whereas the discussion of a generally higher tumor risk in this condition is still controversial. A rare subgroup of KS patients consists of prepubertal children with precocious puberty due to human chorionic gonadotropin (hCG)-producing M-GCTs. We present clinical data on a boy with KS and sexual precocity, and summarize the published data on 12 boys with KS out of 54 cases of KS and M-GCT. Clinical report: an 8.5-year-old boy presented with signs of precocious puberty. Laboratory analyses (suppressed gonadotropins, elevated testosterone) and thoracic CT demonstrated a beta-human chorionic gonadotropin (beta-hCG) and alpha(1)-feto protein (alpha-FP) secreting mediastinal tumor. Histological analysis showed a mixed germ cell tumor comprising choriocarcinoma (CH), embryonal carcinoma (EC), mature teratoma (MT), and yolk sac tumor (YS). He was successfully treated by surgery and adjuvant chemotherapy. Epianalysis of published cases: all KS patients (n = 12), age 4-9 years, presented with precocious sexual development (PP), whereas the older ones showed thorax-associated symptoms, mainly chest pain, dyspnea, and cough. The histological distribution was also age-dependent with mixed germ cell tumors predominantly in younger patients. Thus, M-GCTs are strongly associated with precocious puberty in young boys with KS. Therefore, a karyotype analysis should be included in the clinical work-up of boys with precocious puberty and M-GCT. There is still no convincing explanation for the association of M-GCTs and KS.     

Fragile-X Syndrome: Diagnosis and Research

Fragile-X syndrome, first described in 1969, is named for achromosomal anomoly now known to be a significant cause of mentalretardation in males. An X-linked characteristic, fragile-Xsyndrome is estimated to affect 1 in every 1,000 births andthus is almost as prevalent as Down syndrome. This pattern ofinheritance suggests that identification by psychologists ofpersons with attributes associated with the disorder could leadto identification of affected families and offer opportunityfor contribution to research in the area. However, a surveyat the 1983 American Psychological Association convention revealedthat psychologists in general are unaware of fragile-X syndrome.In addition, a critical review of the fragile-X syndrome literaturesuggests that studies generally have been poor in quality andhave yielded inconclusive findings. A review of studies addressingfactors associated with fragile-X syndrome is presented andseveral areas of research to which psychologists could contributeare discussed.     

Klinefelter syndrome and two fragile X chromosomes

Two fragile X chromosomes were found in 20% of the cells in a moderately mentally retarded patient with Klinefelter syndrome.     

克氏综合征基因表达谱分析

目的 对克氏综合征（Klinefelter syndrome）患者进行基因表达谱分析,探讨其基因差异表达与临床表型之间的关系.方法 采用第二代高通量测序方法对7例克氏综合征患者和7例对照男性外周血全基因组mRNA进行深度测序,运用定量RT-PCR方法对30例克氏综合征患者及30例对照男性进行验证.结果 测序结果根据FDR≤0.001和｜ log2 Ratio≥1 ｜的标准,两组比较存在差异表达基因216个,差异具有统计学意义.其中X染色体基因9个,占4％,与X染色体失活相关的XIST差异表达最明显;常染色体基因207个,占96％,其中NR4A3、ZKSCAN4、HBEGF、EREG、AREG、NR4A2、CCR5差异表达明显.NR4A3主要.与2型糖尿病有关,HBEGF主要参与促性腺激素分泌过程.Y染色体不存在显著差异表达基因.结论 克氏综合征患者不仅多余X染色体基因差异表达,还有大量常染色体基因差异表达,这可能是克氏综合征临床表型多样化的原因.