[Trisomy 18: ultrasound aspects. Report of 40 cases]. / Trisomie 18: aspects échographiques. A propos de 40 observations.

OBJECTIVE: We describe the different ultrasound findings suggestive of trisomy 18. PATIENTS AND METHODS: We conducted a retrospective study in 40 cases of trisomy 18 diagnosed in the department of obstetrics at the Lille University Hospital between 1988 and 1998. RESULTS: Eighty percent of the women in this series were multiparous. Mean maternal age at discovery of the trisomy as 33.2 years and the mean gestational age was 20.4 weeks. Fifty-five percent of the cases were discovered during the second trimester of pregnancy, 22.5% during the third trimester and 22.5% during the first trimester. One ultrasound abnormality, at least, was detected in 36/40 cases (90%) a percentage that reached 96.8% taking into consideration the ultrasound examinations performed during the second and third trimesters (30/31 cases). The most frequently detected ultrasound abnormalities were: intra uterine growth retardation (IUGR: 50%), poly-hydramnios (42.5%), limb abnormalities (42.5%), cardiac defects (30%), facial abnormalities (37.5%), meningomyelocele (32.5%), digestive abnormalities (32.5%), urinary tract abnormalities (27.5%), lymphangiectasia and cystic hygroma (15%), and single umbilical artery (12.5%). Medical termination of pregnancy (TOP) was performed in 28 cases. There was one spontaneous miscarriage at 8 weeks and one in utero death (IUD) at 39 weeks in a patient who desired to continue her pregnancy. In 6 cases, the issue of the pregnancy was unknown because the patients were lost to follow-up. In 4 cases (10%), pregnancy was continued to delivery of live babies that only survived a few minutes to 7 days. CONCLUSION: The ultrasound signs suggestive of trisomy 18 change according to the term of pregnancy. At the first trimester, most of the signs are nonspecific, such as cystic hydroma or lymphangiectasia, and do not suggest the need for a karyotype. At the end of the second trimester, an association of various signs that alone would not be highly suspect suggest the need for further exploration in search of other signs: early IUGR, associated or not with poly-hydramnios, limb abnormalities, cardiac defects, omphalocele, diaphragmatic hernia, meningomyelocele, enlarged cisterna magna, choroid plexus cysts, single umbilical artery, facial dysmorphism, facial cleft, hydronephrosis.

Excision repair defect in Rothmund Thomson syndrome.

Rothmund Thomson syndrome is a rare autosomal recessive skin disorder. The main clinical feature is poikiloderma appearing in early childhood associated with skeletal abnormalities. Early occurrence of malignancies is another relevant feature. Here we describe the clinical features of 2 patients with Rothmund Thomson syndrome who were investigated for the in vitro DNA repair capacities of blood cells following UVC radiation exposure. DNA excision repair, assessed with unscheduled DNA synthesis following UVC exposure, was decreased in both patients. Such a defect might explain the patients' sensitivity to sunlight and the relatively high risk of cancer associated with this syndrome.

Myotonic dystrophy and pregnancy. A report of two cases and a review of the literature.

Myotonic dystrophy is a rare disease (1/8000), that is rarely associated with pregnancy, due to the fact that parents carrying the disease often encounter hypogonadism. Myotonic dystrophy is a neuro-endocrinian 'heredo-degenerative' dystrophy, with dominant autosomic transmission. Its association with pregnancy can lead to several problems. The myotony is often aggravated which leads to obstetrical complications turning into fetal loss, premature term delivery, hydrops, in-utero death, difficulties in expulsion, haemorrhage during delivery and/or anaesthetic accidents. The following signs during the pregnancy can diagnose fetal damage: presence of a hydrops, rare active fetal movements, and low fetal cardiac rhythm. They signify serious fetal damage leading to a diagnosis of myotonic dystrophy. Personal and family antecedents as well as an important hypotony and respiratory distress discovered in the new born are equally evocative elements. In congenital cases (6-30% of the time) the prognosis of the child is pessimistic. For all of the above elements, transmission is of maternal origin. The diagnosis of the congenital form is difficult because the disease is often unknown by the mother. The appearance of molecular tools permits a diagnosis to be formed much more rapidly in a new-born suspected to carry the illness of neonatal Steinert. Two observations illustrate this pathology. The occurrence of congenital myotonic dystrophy in a new-born allows us to diagnose the disease within the mother.

[Prenatal diagnosis of partial trisomy 9p]. / Diagnostic anténatal d'une trisomie 9p partielle.

The prenatal diagnosis of trisomy for the distal half of the short arm of n(o) 9 chromosome (partial trisomy 9p) has been realized from a morphologic ultrasound. A genetic investigation has permitted to establish that this trisomy was due to a bad segregation of a stable translocation present in the patient's mother. To our knowledge, the ultrasound prenatal diagnosis of partial trisomy 9p has never been reported in the literature. The prognosis of this syndrome remains very pejorative and the termination of pregnancy is the most often proposed solution.

Prenatal diagnosis of Roberts syndrome: two new cases.

We report two fetuses with typical anomalies of Roberts syndrome. Prenatal diagnosis was confirmed by the characteristic disjunction of centromeres in amniocytes. We compare these cases with a child who presented with severe Roberts syndrome. We attempted to evaluate quantitatively the centromeric abnormality and the chromosome separation in the different cultures and with different methods. The variability of the clinical manifestations and cytogenetic investigations of this syndrome are reviewed.

Keratoderma with scleroatrophy of the extremities or sclerotylosis (Huriez syndrome): a reappraisal.

Keratoderma with scleroatrophy of the extremities, also referred to as Huriez syndrome, is a rare, autosomal dominant condition, first described in 42 of 132 members of two families from northern France. The term sclerotylosis was proposed because of the pseudosclerodermatous appearance of the hands and digits. The distinctive feature of this syndrome is the risk of the development of squamous cell carcinoma on affected skin. Since the initial description of this disease, three other families, and possibly a fourth, have been reported. In the present study, we reassessed the clinical, pathological and genetic data in 114 members of one of the two original families, of whom 27 were affected by this syndrome.

[Familial thymoma and translocation t (14;20) (q24;p13)]. / Thymome familial et translocation t (14;20) (q24;p13).

A familial lympho-epithelial thymoma with constitutional chromosomal translocation t (14;20) (q24;p13) is presented: the thymoma and its particular translocation are present in the mother and the two sons of her offspring. The small number of cases do not allow establishing any relation between thymoma and this particular translocation. Concerning genetic counseling, an annual thoracic radiography is necessary for all the other family members, carriers or not of the translocation.

[Partial 12q trisomy and chylothorax]. / Trisomie partielle 12q et chylothorax.

The authors present a case of partial trisomy 12q associated with chylothorax, diagnosed at 30 weeks of pregnancy. Cordocentesis for the karyotype as well as thoracocentesis were carried out. In spite of the administration of tocolytic drugs the patient delivered a girl with multiple clinical abnormalities, who died at 7 days of age. From this case, the authors report 6 other cases of partial trisomy 12q in the literature, and, in the discussion they suggest the management after the diagnosis of hydrothorax has been made by ultrasound.

BrdU related direct revelation of typical dynamic R- and G-banding with the use of monoclonal anti-BrdU antibody.

Pulse 5-bromodeoxyuridine (5-BrdU) incorporation during the last S-phase is known to produce R- or G-banded chromosomes after photolysis-plus-Giemsa (FPG) staining. The authors applied an immunological staining with monoclonal anti-BrdU antibody instead of the FPG protocol. The results offered banded chromosomes with an immunological typical R-banding (RBI) on the GBG cultivated cells (early pulse incorporation), and an immunological G-banding (GBI) on the RBG cultivated ones (late pulse incorporation). After a further FPG protocol following an immunological treatment, an inverted banding pattern became evident whereas a faint immunological staining remained. Thus the method superimposed a GBG-banding on the RBI-staining or a RBG on the GBI one. This allows a rapid and easy R and G double chromosomal identification on the same metaphase cell, using first the immunological banding then the classical FPG staining. The method allows a reproducible dynamic G-banding with an easy monitored late 5-BrdU pulse incorporation specially attractive in spontaneous dividing cells from bone marrow. This dynamic G-banding protocol should be extended to chorionic villi and malignant cells. Our data are in agreement with a connection between dynamic banding and chromosomal portions containing or not BrdU. The lack of an immunological staining after the FPG protocol has been noticed and assume the photolysis degradation-elution of the DNA in BrdU-substituted areas.

Cytogenetic and molecular investigations of an abnormal Y chromosome: evidence for a pseudo-dicentric (Yq) isochromosome.

A derivative Y chromosome was found in a 55-year-old man with Lambert-Eaton paraneoplasic pseudomyastheniform disease. Small testicles, azoospermia were noticed and hormonal level values were as in the Klinefelter syndrome. A 45,X/46,XYp+ mosaïcism was described on peripheral blood lymphocytes. Cytogenetic investigations with R-G-C- and Q-banding have been performed. In situ hybridization with the GMGY 10 DNA probe showed two copies of proximal Yp sequences. Southern blot analyses were performed using the Y DNA probes 27a, 47z, 64a7, 50f2 disclosing specific Yp and Yq sequences from the pseudoautosomal boundary to the Yq proximal portion. The der(Y) has been defined as a dicentric isochromosome for the long arm with one active and one apparently suppressed centromere. The breakpoint leading to the der(Y), has been located in the pairing segment of the Y short arm (i.e. Yp11.32). So the der(Y) was interpreted as a psu dic(Y) (qter-->cen-->p11.32 ::p11.32-->qter). There was thus an almost complete duplication of the Y chromosome.

Routine cytogenetic prenatal diagnosis using dynamic banding (RBG-GBG): a highly reproducible method for amniocytes, fetal cord blood, and chorionic villus investigations.

Dynamic banding (RBG-GBG) using pulse 5-bromodeoxyuridine (5-BrdU) incorporation during part of the last S-phase before harvesting has been used in prenatal investigations. This method has already been routinely applied in 1344 cytogenetic investigations. GBG and RBG bandings produced almost identical patterns to classical G- and R-banding methods except for heterochromatic portions and some euchromatic segments. Nevertheless, these discordances may be somewhat helpful for cytogenetic diagnosis (i.e., X numerical abnormalities). The results showed particularly good contrast and staining; 5-BrdU incorporation did not prevent additional staining. Likewise, previous RBG or GBG disclosure allowed further chromosomal identification with C-banding or nucleolar organizer staining. Simplicity and reproducibility were very helpful in cases with a low mitotic index. 5-BrdU had no significant effect on in-vitro damage because only 0.31 percent of cells were affected; so, we believe that dynamic banding should be used more extensively in cytogenetic investigations. Moreover, the staining and contrast qualities were very suitable for automatic methods of analysis now in use: i.e., metaphase finding and computer-assisted karyogram creation.

Prenatal diagnosis of PIBIDS.

In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6-12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2-13.5 per cent of residual activity.

Trisomy 16q23----qter arising from a maternal t(13;16)(p12;q23): case report and evidence of the reciprocal balanced maternal rearrangement by the Ag-NOR technique.

We describe a female new-born with partial trisomy of the long arm of chromosome 16. The chromosome anomaly was the result of an unbalanced segregation of a maternal translocation t(13;16)(p12;q23). Dynamic (RBG, GBG) banding and the Ag-NOR technique ascertained the reciprocal balanced maternal translocation between the 16q23----qter and 13q12----pter segments because nucleolar organizers were present on the tip of long arms of the derivative 16 maternal chromosome. As monosomy 13p has little or no deleterious effect we consider our case as exhibiting the phenotype of trisomy 16q23----qter free from any monosomic feature. Clinical effects are of less consequence as compared with previously published cases of partial trisomy 16q.

Routine autoradiographic analysis of DNA excision-repair. Report of prenatal and postnatal diagnosis in eleven families.

DNA excision-repair of UV induced damages was investigated by unscheduled DNA synthesis and quantitative autoradiography. The method has been routinely used on lymphocytes for postnatal diagnosis of xeroderma pigmentosum and PIBIDS syndrome. Ten XP-families including 13 clinical XP patients and 9 XP-risk children, and one family with one clinical PIBIDS case and one PIBIDS-risk child were screened. Each of the 14 affected patients were biologically ascertained with a significant excision-repair defect. Among the 9 XP-risk children without clinical manifestations, the DNA excision-repair was defected in 4 cases considered as biological XP, and normal in 5 cases considered as biologically normal subjects. Likewise the PIBIDS-risk child exhibited a normal excision-repair. According to the age of the XP or PIBIDS-risk children, and the delay of appearance of clinical manifestations, the method should not present neither false positive nor false negative results and allows the infraclinical diagnosis. The protocol was extended for prenatal diagnosis on amniocytes and fetal cord blood. Excision-repair analysis on normal cultivated chorionic villi cells has been performed allowing a further first trimester prenatal diagnosis.

RFLPs tightly linked with cystic fibrosis: value of probes at the D7S23 locus in prenatal diagnosis.

In a 1:4 risk family, the usefulness of probes at the D7S23 locus for prenatal diagnosis of cystic fibrosis is discussed by comparison with probes at the MET, D7S8, and D7S18 loci that did not allow accuracy in this family.

[Ichthyosis linked to the X chromosome. Biochemical and endocrinologic study]. / Ichtyose liée au chromosome X. Etude biochemique et endocrinienne.

The case of a 6-year-old male patient suffering from X-chromosome-linked ichthyosis is presented. There was no steroid sulfatase activity in the proband's leucocytes and cutaneous fibroblasts. The activity was decreased in the proband's mother's leucocytes and in one brother, affected by a mild ichthyosis. Basal plasma levels of dehydroepiandrosterone and its sulfate were normal for the patient's age, suggesting that sulfates do not play a significant role in the production of free steroids. After 3 intramuscular injections of 1,500 units of human chorionic gonadotropin, plasma levels of testosterone increased normally, indicating that there was no associated primary gonadal insufficiency.

Translocation t(1;19)(q23;p13) in acute lymphoblastic leukemia. A report on six new cases and an unusual t(17;19)(q11;q13), with special reference to prognostic factors.

We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.

Interstitial deletion of chromosome 15: two cases.

Two cases of interstitial deletion of chromosome 15 with similar clinical features are presented. In one case, assay of hexosaminidase A enabled us to confirm that the structural gene is located between 15q22 and 15q25 and that it is included in the deletion.

Acute lymphocytic leukemia with 9p anomalies. A report of four additional cases and review of the literature.

Childhood acute lymphocytic leukemia (ALL) with partial deletion of the short arm of chromosome 9 (9p-), particularly in the p21-22 region, associated with bulky disease, has been regarded as a possible subgroup of ALL. We have reviewed clinical and cytologic data in 128 cases of ALL (childhood and adult). Four of them had 9p anomalies. Two patients had a deletion in the 9p21 region associated with another deletion (9p13----pter) in one case and with t(1;19)(q21;p13) in the second patient. A third patient had a t(9;14)(p21;q12) balanced translocation associated with 14q22----qter deletion; the last patient showed a t(5;9)(p14;q21) unbalanced translocation also associated with 14q deletion. All four patients had lymphomatous ALL, but immunophenotype was non-T, in the four cases, (non-T, non-B in two patients and common ALL in the two remaining cases). Acute lymphocytic leukemia with 9p anomalies appears relatively frequently and is usually associated with poor prognostic features (i.e., bulk disease and high leukocyte counts) but does not seem restricted to childhood and T-cell lineage.