Hanna Dar

Inherited inverted duplication of X chromosome in a male: Report of a patient and review of the literature

Nineteen cases of duplication of segments of the long arm of chromosome X have been published in 13 males and in 6 females. We report an additional case of a male with growth and mental retardation, growth hormone deficiency, compensated primary hypothyroidism, distinctive anomalies of the face, hypoplastic genitalia, and hypotonia in whom inverted duplication of a segment in the long arm of X chromosome was diagnosed, 46,Y, dup (X)(q21.2q13.3), and mosaicism was demonstrated in his mothers X chromosome. The rearranged segment was diagnosed utilizing high resolution G-band technique and FISH studies, using chromosome X total chromosome probe and DNA XIST probe. This appears to be the first report of a patient with duplication of Xq and hypothyroidism.

Prenatal diagnosis of Down syndrome: Ten year experience in the Israeli population

Second trimester maternal serum biochemical markers, introduced between 1990 and 1995, were supplemented with new ultrasound methods at 14–16 weeks and first trimester biochemical markers between 1995 and 2000. This study evaluated the effectiveness of a Down syndrome (DS) prevention program among the Israeli Jewish population between 1990 and 2000. We collected data on the total number of prenatal tests performed on Israeli Jewish women, DS cases detected prenatally and DS livebirths in Israel during these years. We also studied the use of the newer screening tests in 1990, 1992, and 2000. Between 1990 and 1995, use of chromosomal studies for DS in this population increased from 11.3% to 21.6% and the percentage of cases detected prenatally from 53% to 70%. However, between 1996 and 2000, even with the new screening methods, the utilization rate remained similar (20.7% and 19.8%, respectively) and the percentage detected prenatally decreased to 61% in 2000. The total cost per case detected increased from

Very Low Maternal Serum Unconjugated Estriol and Prenatal Diagnosis of Steroid Sulfatase Deficiency

47,971 in 1990 to

Interstitial deletion (6)q13q15.

75,229 in 1992, and to

Deletion (4)(q33 --> qter): a case report and review of the literature.

190,171 in 2000. Between 1990 and 1995, improvement in the percentage of cases detected prenatally was associated with a significant increase in the amniocentesis rate—both are attributed to the introduction of second trimester maternal serum biochemical marker tests. Unexpectedly, the introduction between 1995 and 2000 of new genetic methods to assess the DS risk did not improve the percentage detected or reduce the amniocentesis rate, and was accompanied by an increased cost per case detected.

The clinical significance of multiple hair whorls and their association with unusual dermatoglyphics and dysmorphic features in mentally retarded Israeli children.

Twenty-four women out of 7,875 pregnant women who enrolled in a prenatal screening program showed extremely low levels of unconjugated estriol (< 0.15 MOM). In 19 cases, intrauterine fetal death was reported. In 1 case anencephalus was detected. In the remaining 4 cases apparently normal healthy babies (1 female and 3 males) were born following uneventful pregnancies. Physical examination of the 3 boys at 4-6 weeks revealed mild ichthyosis compatible with the X-linked type. Two of them had a positive family history of X-linked ichthyosis. The examination of the girl did not reveal any significant findings. In both cases in which amniocentesis was performed, low levels of steroid sulfatase and arylsulfatase C were found. The prevalence of X-linked ichthyosis in this study is higher than previously reported, i.e. 1:1,300 males. Our results suggest that the prenatal screening program for neural tube defects and for Downs syndrome is useful for the prenatal detection of X-linked ichthyosis as well. These results are in accordance with two recent reports. The implications regarding genetic counseling are discussed.

Unconjugated Estriol as Maternal Serum Marker for the Detection of Down Syndrome Pregnancies

We report on a 2-year-old child with psychomotor retardation, facial and urogenital anomalies. His chromosome constitution was 46,XY, del(6)(q13q15). This case further contributes to the karyotype-phenotype correlation of proximal deletion 6q syndromes.

Detection of X chromosome aneuploidy using Southern blot analysis during routine population-based screening for fragile X syndrome.

Deletions of the long arm of chromosome 4 are apparently quite rare. There have been several reports of isolated terminal deletions of chromosome 4.’ The majority of these have involved deletion of the long arm from band 4q31.2m’ Two reports have described cases of deletion from 4q32 .18, 19 Eight cases in seven reports have involved the terminal portion from q33->qter. 10,11,20--24 Some authors suggested that a &dquo;4q-syndrome&dquo; does exist on the basis of clinical findings,’, 10,21 however, it is claimed that del(4)(q33 -> qter) is a different, milder syndrome.23 We present the ninth case with the q33->qter deletion of chromosome 4, however, with mild dysmorphic features, normal growth, and mild to moderate developmental delay. A tentative diagnosis of Williams syndrome by the referring pediatrician was probably based on the specific heart defects rather than on specific facial features. In two other reports,22,26 the same resemblance was

New multiple congenital anomalies: mental retardation syndrome (MCA/MR) with facio-cutaneous-skeletal involvement.

The prevalence of multiple hair whorls in a group of mentally retarded patients was 8% as opposed to 3.6% in a group of healthy children. A statistically significant relationship was demonstrated between mental retardation, multiple hair whorls, more than two dysmorphic features, and unusual dermatoglyphics. The results confirm the importance of multiple hair whorls as a genuine dysmorphic feature. The significance of these markers in the evaluation of mentally retarded subjects is discussed, with special reference to the timing of the fetal insult.

Neu-Laxova syndrome: Prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations

The effectiveness of unconjugated estriol (uE3) as a serum marker for the detection of Down syndrome (DS) during the 2nd trimester of pregnancy was evaluated. A population of 18,764 normal singleton pregnancies was screened for alpha-feto-protein and human chorionic gonadotropin. In 9,311 women, uE3 was added. Using a risk of 1:250 at term as a cutoff value, the false-positive rates were 4.1 and 4.3% without and with uE3, respectively. The detection rates in 47 DS serum samples, some of which were studied retrospectively, were 66% without uE3 and 57% with uE3. In 12 of 25 younger women and in 19 of 22 older women, DS was detected without uE3. The uE3 contributed to the detection of 4 additional DS pregnancies (1 in the young and 3 in older women). On the other hand, 8 DS pregnancies (3 in younger women and 5 in older women) escaped detection. In our sample the addition of uE3 lowered the detection rate of DS pregnancies with only a small and insignificant effect on the false-positive rate. Our results call for special caution in the addition of markers for risk calculations. We suggest that pregnancies with a calculated risk of > 1:250 following maternal serum alpha-fetoprotein and human chorionic gonadotropin markers tests should be regarded as high-risk pregnancies, even in cases in whom the addition of uE3 lowers the risk beneath the cutoff value.