Fetal transcerebellar diameter and chromosomal abnormalities.

OBJECTIVE: To evaluate the association between chromosomal abnormalities and fetal cerebellar size. DESIGN: A retrospective cross-sectional study. METHODS: Ultrasound measurements of transcerebellar diameter, head and upper-abdominal circumference from 88 fetuses with chromosomal abnormalities were analyzed. Abnormalities included trisomy 21 ( n = 23), trisomy 18 ( n = 17), 'other numerical chromosomal abnormalities' ( n = 9), sex chromosomal abnormalities ( n = 9), mosaicism ( n = 12), balanced translocations ( n = 9) and unbalanced translocations ( n = 9). Multiple regression analysis was performed to compare transcerebellar diameters between the reference group and each of the subsets of chromosomal abnormalities and between trisomies 18 and 21. Also, in the latter two subsets, comparison of the transcerebellar diameter before and after 25 weeks of gestation was carried out. RESULTS: Fetal transcerebellar diameter was reduced in relation to gestational age but was normal when control was made for fetal size in all chromosomal subsets, except for balanced translocations. The transcerebellar diameter in trisomy 18 was significantly smaller than that in trisomy 21. No difference in cerebellar size was found when comparing the gestational age period before and after 25 weeks in each of these two subsets. CONCLUSIONS: A reduction in fetal transcerebellar diameter was demonstrated in all chromosomal abnormalities with imbalance of genetic material. Cerebellar hypoplasia was more severe in trisomy 18 than in trisomy 21. The degree of reduction in fetal transcerebellar diameter in these subsets seems to be independent of the time period during which the transcerebellar diameter measurement was performed.

Prenatal diagnosis and genetic analysis of X chromosome polysomy 49, XXXXY.

We report on the prenatal diagnosis, genetic analysis and clinical manifestations of a 49,XXXXY fetus. A 31-year-old, primigravida woman was referred for genetic counselling at 17 weeks' gestation with the sonographic findings of intrauterine growth retardation, generalized oedema, a large septated cystic hygroma colli measuring 5x4 cm, and abnormal posturing of the lower extremities. Quantitative fluorescent polymerase chain reaction (QF-PCR) with small tandem repeat (STR) markers specific for chromosome X and a pentanucleotide marker X22 for the Xq/Yq pseudoautosomal region PAR2 rapidly detected the X-chromosome polysomy from amniotic fluid cells. This abnormality appeared to arise from successive non-disjunction during maternal meiosis I and meiosis II. Cytogenetic analysis revealed a karyotype of 49,XXXXY. Our case shows that a 49,XXXXY fetus in the second trimester may demonstrate hydrops fetalis and a large septated cystic hygroma colli by prenatal ultrasound. Our case also shows that QF-PCR assays with sex chromosome specific STR markers provide rapid prenatal diagnosis of numerical sex chromosome aneuploidy as well as its genetic cause in fetal cystic hygroma.

Fetal heart rate in chromosomally abnormal fetuses.

OBJECTIVES: To determine the effects of chromosomal defects on fetal heart rate at 10-14 weeks of gestation. METHODS: Fetal heart rate at 10-14 weeks of gestation in 1061 chromosomally abnormal fetuses was compared to that from 25,000 normal pregnancies. The chromosomally abnormal group included 554 cases of trisomy 21, 219 cases of trisomy 18, 95 of trisomy 13, 50 of triploidy, 115 of Turner syndrome and 28 of sex chromosome abnormalities other than Turner syndrome. RESULTS: In the normal group, fetal heart rate decreased from a mean value of 170 beats per minute (bpm) at 35 mm of crown-rump length to 155 bpm at 84 mm crown-rump length. In trisomy 21, trisomy 13 and Turner syndrome fetal heart rate was significantly higher, in trisomy 18 and triploidy the heart rate was lower and in other sex chromosome defects it was not significantly different from normal. Fetal heart rate was above the 95th centile of the normal range in 10%, 67% and 52% of fetuses with trisomy 21, trisomy 13 and Turner syndrome, respectively. The fetal heart rate was below the 5th centile in 30% of fetuses with triploidy and 19% of those with trisomy 18. CONCLUSIONS: Trisomy 21, trisomy 13 and Turner syndrome are associated with fetal tachycardia, whereas in trisomy 18 and triploidy there is fetal bradycardia. Inclusion of fetal heart rate in a first-trimester screening program for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness is unlikely to provide useful improvement in sensitivity.

Prenatal diagnosis of 46,XX male fetuses.

Ultrasonography can accurately determine phenotypic sex differences from those of the genetic sex. Two cases were identified; they were the result of a translocation of the SRY gene from the Y chromosome to the X chromosome during meiosis. An ultrasonographic difference may represent an otherwise unsuspected genetic abnormality.

45,X/46,XY mosaicism: the role of ultrasound in prenatal diagnosis and counselling.

The purpose of this study was to assess the benefit of ultrasound evaluation for fetuses with prenatally diagnosed 45,X/46,XY mosaicism. The charts of all patients who underwent chorionic villus sampling and/or amniocentesis between 1 March 1990 and 31 October 1995 were screened for 45,X/46,XY mosaicism. Cases were divided on the basis of the results of the confirmatory amniocentesis into two groups: (1) confined placental mosaicism (n = 4); and (2) true fetal 45,X/46,XY mosaicism (n = 4). All patients underwent high-resolution detailed ultrasound study between 16 and 22 weeks. If the initial ultrasound study failed to visualize fetal genitalia, scanning was repeated in 2 weeks. Chromosome analysis was carried out on the newborn's skin to confirm the prenatal result. Six cases were found to have 45,X/46,XY mosaicism on chorionic villus sampling. Amniocentesis indicated a normal 46,XY male karyotype for three fetuses and true fetal 45,X/46,XY mosaicism for two cases. One patient declined follow-up amniocentesis. At birth, this newborn was documented to have normal male genitalia and a 46,XY karyotype. An additional two cases underwent amniocentesis only and were documented to have 45,X/46,XY mosaicism. High-resolution detailed ultrasound study between 16 and 22 weeks revealed seven fetuses with normal male genitalia and one fetus with ambiguous genitalia. Of the four neonates with true 45,X/46,XY mosaicism this was the only one found to have ambiguous genitalia. We conclude that the work-up of patients with 45,X/46,XY mosaicism should include ultrasound study to look for ambiguous genitalia. This allows appropriate counselling regarding the natural history of the condition and aids in the planning for management in the postnatal period.

Evolution of bone anomalies in 49,XXXXY syndrome.

Long-term radiologic follow-up, from the age of 1 year to 27 and 28 years respectively, was performed for two patients with the XXXXY chromosome anomaly. The patients remained sexually immature; the major abnormality observed radiologically was delayed maturation of the skeleton, the growth plates persisting into adulthood. Early degeneration of the articular cartilage, particularly at the elbows, was observed, along with hypertrophy of the epiphyses and radiohumeral dislocation. One of the patients had intra-articular osteochondroma of the left elbow of unknown cause. Cerebral computed tomography showed enlargement of the lateral ventricles in both patients and the formation of pneumatic cavities in the parietal bones in one.

Body stalk deformity in a twin pregnancy: case report and review.

Body stalk deformity is a variety of the limb-body wall complex (LBMC)--the rare, complicated, congenital process believed to result from early rupture of the amnion and vascular disruption. Here we report a case of this anomaly in a twin pregnancy and describe the prenatal ultrasound findings.

Prenatal identification of a 45,X/46,Xder(Y) mosaicism and confirmation by high resolution cytogenetics and fluorescence in situ hybridization.

A 45,X/46,Xder(Y) mosaicism detected prenatally was shown to have a rare Y inversion-duplication or Y/Y translocation which can only be identified by a combination of high resolution cytogenetics and fluorescence in situ hybridization. The present data indicate the usefulness and importance of chromosome-specific probes in the identification and characterization of chromosome rearrangements.

A multipedigree linkage study of X-linked deafness: linkage to Xq13-q21 and evidence for genetic heterogeneity.

A locus for X-linked nonsyndromic deafness has previously been allocated to the Xq13-q21 region based on linkage studies in two separate pedigrees. This has been substantiated by the observation of deafness as a clinical feature of male patients with cytogenetically detectable deletions across this region. The question of a second locus for deafness in this chromosomal region has been raised by the audiologically distinct nature of the deafness in some of the deleted patients compared to that observed in those patients upon whom the linkage data are based. We have performed detailed clinical evaluation and linkage studies on seven pedigrees with nonsyndromic X-linked deafness and conclude that there is evidence for at least two loci for this form of deafness, including one in the Xq13-q21 region. We have observed different radiological features among the pedigrees which map to Xq13-q21, suggesting that even among these pedigrees the deafness is due to different pathological processes. Given these findings, we suggest that the classification of nonsyndromic X-linked deafness based solely on audiological criteria may need to be reviewed.

Corpus callosum agenesis, spastic quadriparesis and irregular lining of the lateral ventricles on CT-scan. A distinct X-linked mental retardation syndrome?

This report gives a description of 4 male patients, two of whom are sibs, two of whom are uncle and cousin. They appear to have psychomotor retardation, spastic quadriparesis and on CT (partial) agencies of the corpus callosum, and irregular lining of the lateral ventricles, without craniofacial abnormalities or seizures. Although the mode of inheritance of agenesis of the corpus callosum is still difficult to establish, in these 4 male patients an X-linked recessive inheritance is the most likely mode. A review of the literature with concern to the heredity of agenesis of the corpus callosum is presented. The clinical and neurological findings in the present four male patients allow for the delineation of a new X-linked mental retardation syndrome.

Metacarpophalangeal pattern profile analysis in fragile X syndrome.

We analyzed the metacarpophalangeal pattern profile (MCPP) on 18 male individuals from 16 families with fragile X--fra (X), or Martin-Bell--syndrome and calculated a mean syndrome profile. Fourteen of 18 individuals with fra (X) syndrome had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with fra (X) syndrome compared with a sample of normal individuals produced a correct classification rate of 88% based on a function of 3 MCPP variables that may provide a useful tool in screening individuals for the fra (X) syndrome. Discriminant and correlation analyses of individuals with Sotos sequence and individuals with fra (X) syndrome did not identify MCPP similarities. Therefore, there was no MCPP evidence in our study of patients with Sotos sequence and fra (X) chromosome expression.

Dyskeratosis congenita: radiologic features.

Three males with the X-linked disorder dyskeratosis congenita are described. Each suffered femoral fractures after minimal trauma with poor healing. Long bones showed coarse trabecular patterns of the metaphyses and small lucency areas in the diaphyses. Two of the males were retarded brothers who additionally showed intracranial calcifications.

Increased metaphyseal bone mass in the young X-linked hypophosphatemic (Hyp) mouse.

A study of skeletal development in X-linked hypophosphatemic (Hyp) mice revealed that radiographic characteristics of the disease appear as early as seven days after birth and that an unexpected transitory metaphyseal radio-opacity occurs in the long bones of the Hyp mice. Hyperostotic osteomalacia appears at the first week, peaks at the third week, and starts to fade by the fourth week. Undecalcified bone sections of three-week-old mice revealed an increased amount of trabecular bone in the metaphysis of the Hyp mice accounting for the increased radio-opacity. Blood chemistry data in three-week-old mice showed a low plasma phosphate, a slight hypocalcemia and elevated alkaline phosphatase. Three-week-old Hyp mice had a reduced percentage of magnesium in their bone ash compared to normal. The blood chemistry data resembled those of adult Hyp mice and did not explain the increased metaphyseal bone mass. The mechanism underlying this genetic abnormality of bone is unclear.

[XXXXY syndrome: clinical-radiological findings in one patient (author's transl)]. / Su una osservazione di sindrome XXXXY: rilievi clinico-radiologici.

A case of XXXXY syndrome in a 15 year old male is reported. Clinical findings (mental retardation, muscular hypotonia, hypogonadism, characteristic facies), chromosome analyses as well as fingerprint ridge counts were typical of the syndrome. Several radiological abnormalities were found. It is noteworthy that features consistent with epiphysial dysplasia were present. In the patient's kindred a case of "cri du chat" syndrome and a 5:9 balanced translocation were discovered.

Pneumoencephalographic and clinical findings of the XYY syndrome.

In order to approach the hitherto unknown brain involvement in the XYY syndrome five adult patients with this syndrome were studied clinically and pneumoencephalographically. Clinical manifestations included delayed difficulties of speech and learning, clumsiness, mild intention tremor, muscular hypotonia, convulsions, hyperactivity, distractibility, impulsiveness, weak mental control, psychosexual disturbances and a slight defect of intelligence. All five had committed crimes. Pneumoencephalograms showed general ventricular enlargement of mild or moderate degree. The enlargement of lateral ventricles was unilateral or asymmetrically bilateral. The suprapineal recess of the third ventricle was uniformly enlarged. Small cerebellum and enlarged fourth ventricle were the abnormal findings in the posterior fossa. No cortical abnormalities were found. The clinical and pneumoencephalographic findings suggest a slight non-progressive developmental disorder of the brain resembling the so-called minimal brain dysfunction syndrome. The XYY syndrome appears to be one cause of the male preponderance in minimal brain dysfunction syndrome and criminal psychopathy.

[X-ray anatomic features of the skeleton in the 47, XYY syndrome]. / Rentgenoanatomicheskie osobennosti skeleta pri sindrome 47, XYY.

The data are represented on the examination of 11 men with 47, XYY karyotype, roengenography of some parts of their skeletals including. The result are compared with the data on investigation of 430 human males chosen from a population. This anomaly in the karyotype stipulates, in the skeletal formation, a tendency to high stature, a certain flattening in the head of the radiocarpal articulation, the kneepan and the distal contour of the femoral bone. Nearly in a half of all observations valgus deviation of the ulnar articulation was somewhat increased, in 3 cases--inhibition of some synostoses in the growth zones of the extremities was noted. A supposition is made that in males the insidence of cleft in sesamoid bones in the lower extremities is increased in the presence of the extra Y-chromosome.

Abnormal basal angle of the skull in sex chromosome aberrations.

The basal angle was measured on skull films in 252 patients with hormonal disorders and sex chromosome aberrations. In cases of hormonal disturbance the basal angle was normal. In patients with Turner's syndrome (45,X chromosomes) the basal angle was enlarged while in patients with Klinefelter's syndrome (47,XXY chromosomes) and in those with extra X or Y chromosomes it was definitely reduced. A close relationship exists between the sex chromosome number and the size of the basal angle.