[A case of Ullrich disease with distinct pathological change of muscular dystrophy].

A case of Ullrich disease was presented. The patient was a 3-year-old girl with torticollis, generalized muscle weakness and acroatonia since birth. High-arched palate, protruded calcaneus, and mild contracture of proximal joints were also recognized. Intellectual development was normal. Serum level of CPK was slightly increased. In histological and histochemical examinations of quadriceps femoris muscle, proliferated connective tissue, marked variation in the muscle fiber diameter, and a lot of degenerated and regenerated fibers were recognized. Minimal injury easily causes subcutaneous hemorrhage, but no abnormality was found in the structure of collagen.

Clinico-neurological investigations in the fra(X) form of mental retardation.

A clinical, neurological and electroencephalographic investigation was undertaken in 29 previously cytogenetically verified hemizygous males with the fra(X) form of mental retardation (age range 3.5 to 59 years); in addition, 6 heterozygous females were examined. All male patients displayed the known physical aspects of this syndrome together with associated abnormalities of the palate, skeleton, connective tissue and endocrine system. The most prominent neurological features were different forms of oculomotor disturbances, minor motor and pyramidal signs, incoordination, muscle hypotonia, gait and speech abnormalities. There was no increased frequency either in seizures or in epileptic EEG discharges. Some patients had a slowing of background activity in EEG. About 50% of all patients displayed autistic-like behaviour, short attention span and/or hyperactivity. In accordance with the literature, the findings indicate that there are no neurological, electroencephalographic or neuroradiological features which occur specifically in this syndrome. The need to differentiate the findings from those resulting from encephalopathic mechanisms during the gestational and perinatal period is stressed. A distinct typing of seizures and EEG changes is needed in each patient, before definite conclusions about an association of seizures and fra(X) syndrome are drawn. In view of the lack of correlation between IQ and the clinical-neurological measures, a more practical approach to quantifying the mental impairment is proposed.

Inherited pericentric inversion of Y-chromosome with trisomy 21. A case report.

A 13-year-old boy with clinical features of Down syndrome was investigated. His karyotype was 47,X,inv(Y),+21. The proband's father and two elder brothers were also found to have the inv(Y). A spontaneous chromatid break was observed in the long arm of the X chromosome[? fra (X)] in 2% of the cells. The mother had two spontaneous abortions. This is the first case of trisomy-21 with inv(Y) in our population. This finding might be fortuitous. The frequency of inv(Y) in Down syndrome is not known.

Do some patients with fragile X syndrome have precocious puberty?

We report on an 8 1/2-year-old white girl with fra (X) syndrome; she had mental deficiency, hyperactivity, speech disturbances, slightly prominent ears, mild joint laxity and 20% fra (X) expression. Additional findings include idiopathic precocious puberty and a right ovarian cyst. Ovarian cysts have been reported previously in heterozygous females, but to our knowledge idiopathic precocious puberty is a new finding in this syndrome. Whether precocious puberty is a coincidental finding in this patient or a previously unreported manifestation of the fra (X) syndrome is not clear.

Fragile X syndrome and acute lymphoblastic leukemia.

Fragile X [Fra(X)] syndrome is an example of a heritable fragility syndrome associated with mental retardation. It is characterized by a fragile site on the X chromosome at Xq27-28. There have recently been three reports of malignant solid tumors associated with Fra(X) syndrome. We describe the first case of a hematologic malignancy [T-cell acute lymphocytic leukemia (ALL)] in a patient with Fra(X) syndrome. The possibility of a predisposition to malignancy in Fra(X) is discussed.

47,XXX: what is the prognosis?

Eleven unselected 47,XXX girls, now 15 to 22 years of age, have been observed from birth in a prospective study of children with sex chromosome anomalies. A description of their growth and development is presented. The 47,XXX infants were not generally distinguishable from chromosomally normal children in the first year of life, even though there was a slight delay in neuromotor development. By 2 years of age, developmental delays in speech and language often became evident, and speech therapy was often necessitated in the preschool years. Early school problems included speech and language deficiencies, lack of coordination, poor academic performance, and immature behavior; these persisted throughout the school years. By high school age, a 47,XXX girl was generally tall and often subject to somatic complaints. Sexual development was generally normal. Seven of the 11 propositae had a diagnosed psychiatric disorder or disturbance at some time during adolescence. Variability within this syndrome is great; one proposita is in college and another is mentally retarded. The frequency of the diagnosis of the 47,XXX karyotype by genetic amniocentesis is estimated to be 1/1000, the same incidence as in the newborn population. Expectant parents must be counseled as to the significance of this karyotype and prognostic information must be given. Suggested guidelines are included.

Fragile X syndrome: genetic predisposition to psychopathology.

Fragile X syndrome is a newly recognized X-linked disorder which has been associated with a high prevalence of psychiatric disturbance, particularly attention deficit disorder and autism. The present study involved the neuropsychiatric evaluation of 14 males with the disorder who were between the ages of 3 to 27 years. Pervasive hyperactivity, impulsivity, and attentional deficits were found among all of the subjects, while a significant degree of anxiety was manifested by more than half. Although the majority of subjects exhibited poor eye contact, atypical speech and language functioning, and stereotyped behavior, only one met DSM-III diagnostic criteria for a persistent pervasive developmental disorder. Gaze aversion, noted among half of the subjects, was attributed to underlying anxiety rather than to autistic social dysfunction because of the otherwise socially engaged and affectionate behavior exhibited by the subjects. Failure to make this distinction in the context of cognitive and linguistic impairments associated with fragile X syndrome may account for the high rates of autism reported by other investigators.

[Identification of aberrant chromosomes based on the morphometry of the synaptonemal complexes in a sterile male mouse]. / Identifikatsiia aberrantnykh khromosom na osnove morfometrii sinaptonemnykh kompleksov u steril'nogo samtsa myshi.

The synaptonemal complexes (SCs) of surface-spread spermatocytes of male mouse from the F1 progeny of a male exposed to a mutagen have been examined by electron microscopy. Nonreciprocal translocation was recognised in analysing configuration of SC. Electron microscope analysis revealed translocation in 100% pachytene spermatocytes and light microscope analysis of air-dried metaphase spermatocytes demonstrated this in 58% cells. Different types of association of X-chromosome with aberrant chromosomes were discovered in pachytene spermatocytes. Computer analysis of relative length of SCs permits to detect a nonreciprocal translocation from chromosome 4 to chromosome 16. The length of the translocated fragment was determined to be from 66 to 75% of the length of chromosome 4. It has been impossible to discover a telomere fragment of chromosome 16, because the break point of chromosome 16 is too close to the distal end.

Fragile X syndrome and neoplasia.

Among 100 males with fragile X [fra(X)] or Martin-Bell syndrome, two have developed malignancies. The first case, a 57-year-old man with fra(X) expression in 12% of peripheral blood lymphocytes, developed a seminoma of the left testis at age 45 years and in the right testis at age 50 years. The second case, a 16-year-old white boy with fra(X) expression in 23% of lymphocytes, developed a mucin-producing adenocarcinoma of the colon at age 14 years. Because of the unusual nature of the tumors observed in these patients and in 2 other patients from the literature, we suggest that individuals with the fra(X) syndrome may be at increased risk of cancer.

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.

Fragile X syndrome and nephrogenic diabetes insipidus.

We describe a man with the fra(X) syndrome and nephrogenic diabetes insipidus. The disease loci for both conditions are in the region Xq27.3-q28. This is the first report of the fra(X) syndrome associated with another X-linked disorder. Analysis of DNA markers suggested that the association in this man was coincidental.

Fragile-X mutation and Klinefelter syndrome: a reappraisal.

To date the concurrent presence of the fragile-X and the Klinefelter syndromes in the same individual has been found at least 8 times either in the course of screening for the fra(X) condition in mentally retarded males or among the relatives of fra(X) propositi. Given the high frequency of both events in the general population and the heterogeneous approaches with which the above cases were ascertained, it has not been possible to determine unequivocally so far whether the finding is purely coincidental or the expression of some underlying biological relationship. To evaluate the issue, we have screened a large population of institutionalized mentally retarded males for microorchidism, and submitted to a full karyotype analysis and fra(X) testing the patients that were found to have marked bilateral microorchidism. Thus, in a total of 32 microorchidism patients identified among 1115 mentally retarded males, we found 6 to have a 47,XXY chromosome complement in all (or in most) of their cells, with one of them having also the fra(X) marker in 9% of the metaphases examined. In addition, another bearer of the fra(X) marker (but only in 4% of his metaphases) was found among 26 47,XXY mentally normal males ascertained throughout routine cytogenetic analysis of males with microorchidism referred to our genetic counseling unit during the last 10 years. In our laboratory the fra(X) marker has never been observed with such a frequency in a total of several hundred normal XY males and XX females studied as control cases in the course of previously reported family and population studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a (Y;4) translocation by DNA hybridization.

A phenotypically normal male with azoospermia was found to have a translocation between the short arm of the Y chromosome and the distal long arm of a chromosome 4. By cytogenetic analysis it could not be determined whether the translocation was reciprocal, nor whether it was balanced. In situ DNA hybridization with two pseudoautosomal and one Y-specific probe demonstrated that the breakpoint was on distal Yp and that there was Y chromosome material on 4q. Thus the translocation was reciprocal and could be characterized as t(Y;4)(pll;q32). There was no evidence for loss of Y-DNA sequences as judged by Southern blotting with Y-DNA probes. Thus the translocation may be balanced. We conclude that DNA hybridization can be used to refine considerably the cytogenetic analysis of such translocations.