Discordant sex in monozygotic XXY/XX twins: a case report.

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.

[Virilizing ovarian tumors in the menopausal patient]. / Tumeurs virilisantes de l'ovaire chez la femme ménopausée.

Virilizing ovarian tumors are rare and can occur at any age. In postmenopausal women, they commonly present with signs of masculinization. These tumors should be suspected in any patient with virilization and high testosterone levels (>1ng/mL). Tumor localization is sometimes difficult. These tumors are usually benign; surgical resection is the accepted treatment. Masculinizing consequences of hormonal secretions may be managed by cosmetologic treatments which should not be overlooked.

[Multiple myxomata: about one case]. / Myxomes multiples: à propos d'un cas.

Among the primitive cardiac tumours, myxoma is the most common. This benign tumour is sometimes described in the context of Carney's syndrome, in which cardiac myxoma, cutaneous myxoma, lentigo and pigmentary nevus cutaneous lesions, endocrine disorders, and testicular, thyroid and hypophyseal tumours are associated. The cardiac myxomata observed are multiple, recurrent, and involve the four cardiac chambers, with a peak incidence at 25 years of age. These observations may exist in a familial context, linked to an autosomal dominant genetic factor, localized on the 17q2 chromosome with polymorphism of the PRKAR1a gene. As in the case of sporadic myxoma, rapid surgical treatment with cardio-pulmonary bypass is indicated, bearing in mind the increased risk of thromboembolic phenomena and sudden death from valvular encroachment. We report a case of bi-atrial myxoma observed in the context of Carney's syndrome.

Multicolor PRINS and multicolor PNA.

Both PRimed IN Situ (PRINS) and Peptide Nucleic Acid (PNA) technologies have emerged as research techniques, but they have quickly evolved to applications in biological diagnosis assays. The two procedures now constitute efficient alternatives to the conventional fluorescence in situ hybridization (FISH) procedure for in situ chromosome identification and aneuploidy detection. They present several advantages (specificity, speed, discriminating ability) that make them very attractive for a number of cytogenetic purposes. Multicolor PRINS and PNA protocols have been described for the specific identification of human chromosomes. Various applications have already been developed in human genetics and new adaptations are ongoing.

[Osteochondritis dissecans of the femoral condyles: report of 892 cases]. / L'ostéochondrite disséquante des condyles fémoraux.

PURPOSE OF THE STUDY: Osteochondritis rarely involves the femoral condyles. Discovery in this localization raises several questions concerning the nature of the articular cartilage, the potential for spontaneous healing, and, in the event of a free fragment, the outcome after its loss or repair. MATERIAL AND METHODS: This multicentric study included 892 pediatric and adult cases, the cutoff between two series being defined by fusion of the inferior growth plate. We excluded medical or surgical osteochondritis, cases involving the patella, osteochondral fractures, juvenile polyosteochondrosis, adult osteonecrosis, and osteochondritis beginning after the age of 50 years. RESULTS: Mean age at diagnosis was 16.5 years. Mean age at treatment onset was 22 years. Pain was the predominant symptom. 80% of cases were unilateral and 70% involved the medial condyle. The anatomic lesions were different in adults, showing more advanced degradation. At diagnosis, Bedouelle stages Ia and IIb constituted 80% of the cases observed among children while in adults, 66% were Bedouelle stages IIb to IV. Outcome was very good for the majority of children with Hughston clinical stage 4 while half of the x-rays were Hughston stage 3 and 4. There were thus a large percentage of children with abnormal xrays whose disease history was not yet terminated. In the adult series, the percentages of Hughston 3 and 4 was about the same as clinically. The x-rays were rarely perfectly normal since half of the clinical stage 3 patients were noted in stage 4. An abnormal x-ray with a very good clinical presentation was observed in a very large proportion of patients. DISCUSSION: It is difficult to interpret the plain x-ray and identify patients with a potentially unfavorable prognosis. We defined three radiographic classes: defect, nodule and empty notch. The Bedouelle classification uses information from all available explorations, particularly MRI and arthroscopy. Numerous therapeutic methods are used. Interruption of sports activities is the first intention treatment for children. Data in the literature and the findings of this symposium do not demonstrate any beneficial effect of immobilization on healing compared with simple abstention from sports activities. Transchondral perforation is a simple operation with low morbidity. In 85% of cases, it was used for lesions with an intact joint cartilage considered stable in 96% of cases. Healing was achieved in six months for 48% if the growth plate had not fused. The fragment was fixed in 43% of the cases with a loose cartilage fragment. Outcome was fair but degraded with the state of the joint cartilage and thus the stability of the fragment. Fixation must stabilize the fragment but not prevent further consolidation via osteogenesis. This is why deep perforations are drilled beyond the ossified area and additional osteochondral grafts are used. The Wagner operation gives less satisfactory results than more complicated procedures. Removal of a sequestrum is a simple, minimally invasive procedure with an uneventful postoperative period, but in the long term it favors osteoarthritic degradation, especially when performed in adults. Mosaic grafts give good mid term results. Morbidity is low especially if the grafts are harvested above the notch. The question of chondrolysis around the grafts was beyond the scope of this study. Chondrocyte grafting is difficult to accomplish and is expensive. The mid term results are good for large lesions. Osteotomy is logical only in the event of early stage osteoarthritic degradation. DECISION ALGORITHM IN CHILDREN AND ADOLESCENTS: If the plain x-ray reveals a defect (class I), simple interruption of sports activities should be proposed. Two situations can then develop. First, in a certain number of patients, the pain disappears as the defective zone ossifies progressively. Complete cure is frequent before the age of 12 years. In the second situation, the knee remains painful and the x-ray does not change or worsens to a class II nodular formation. In this case an MRI must be obtained to determine whether the joint cartilage is normal. There are two possibilities. First, the osteochondral fragment is viable and most probably will become completely re-integrated, particularly if the lesion is far from the growth plate. Necrosis is the other possibility. Transchondral perforations are needed in this case. If on the contrary the cartilage is altered, there is little hope for spontaneous cure. Arthroscopy may be needed to complete the exploration. Fragments, especially if there is a large surface area, must be fixed. Perforations to favor revascularization are certainly useful here. In the last situation (class III), the fragment wobbles on a thin attachment or has already fallen into the joint space. This is the type of problem generally observed in adults. The decision algorithm in adults is the same as in children for the rare nodular aspects (class II). There could be a discussion between transcartilage perforation and fixation. If there are a large number of fragments, fixation may not be fully successful and the lesion might be considered class III. For class III lesions, three operations can be used: removal of the sequestrum, mosaic bone-cartilage grafts, or autologous chondrocyte grafts. At the same follow-up, mosaic grafts give better results than excision of sequestra. It may be useful to remove sequestra in a limited number of situations: if there is just a small area of osteochondritis, the lesion is old and partially healed, or the zone is non weight-bearing. For other lesions, we favor mosaic grafts. We still do not have enough follow-up to assess the long-term outcome with these mosaic grafts, but simple excision clearly favors osteoarthritic degradation. Can chondrocytes grafts be compared with mosaic grafts? Chondrocyte grafts have been used for very large lesions and have given results similar to mosaic grafts. It might also be possible to combine fixation of a loose fragment and a mosaic graft. LESSONS FROM THIS STUDY: 1) The prognosis of osteochondritis is better before than after fusion of the growth plate but the lesion does not always heal in children. 2) Presence of osteochondritis requires complementary anatomic and functional exploration to determine the stability and the vitality of the fragment. 3) Attention must be taken to perform transchondral perforations early enough, particularly in children. 4) Screw fixation is not always sufficient. The trophicity of the fragment and its blood supply must be improved. 5) Mosaic grafts are preferable to excision of the fragment. 6) Chondrocyte grafts will be more widely used in the future.

[Percutaneous rotational osteoclasis in management of congenital radio-ulnar synostosis]. / Ostéotomies percutanées de dérotation de l'avant-bras dans les synostoses radio-ulnaires congénitales de l'enfant.

PURPOSE OF THE STUDY: Congenital radio-ulnar synostosis blocks the wrist in a position of more or less pronounced pronation. The degree of pronation and possible bilateral involvement can compromise upper limb function. We propose percutaneous osteoclasis of the antebrachial skeleton to remedy this situation PATIENTS AND METHODS: We performed 12 percutaneous rotation osteoclasis procedures. The objective was to weaken the metaphysodiaphyseal cortical periosteum of one or both of the forearm bones by intermittent perforations. This enabled derotation of the wrist which was maintained for six to eight weeks in a brachiopalmar cast. RESULTS: Mean correction of pronation was 51 degrees. There were no cases of vascular or nervous complications and healing was uneventful. The esthetic outcome was very satisfactory. DISCUSSION: Surgery is not indicated for all cases of synostosis. We retain for surgery patients presenting pronation at 60 degrees or more. At this degree of pronation, function is greatly compromised in adolescence, particularly if there is a bilateral involvement. Compared with other techniques, percutaneous osteoclasis is a simple safe and reliable technique. Reoperation is not required to remove material. The procedure is easier in young children, preferably at the age of 3 to 7 years, before the development of a functional handicap.

[Management of Lagrange and Rigault stage IV extension type supracondylar fracture of the humerus in children]. / Prise en charge des fractures supracondyliennes en extension stade IV de Lagrange et Rigault.

PURPOSE OF THE STUDY: Lagrange and Rigault stage IV extension type supracondylar fracture of the humerus (Gartland and Wilkins type III) involves major displacement, making treatment difficult. Several therapeutic methods have been described but indications vary considerably between teams. We conducted a retrospective analysis in order to evaluate the results of different methods, identify the most adapted technique, and detail the conditions necessary for good results with the collar and cuff immobilization method described by Blount. MATERIAL AND METHODS: Forty-four children (30 boys and 14 girls), mean age seven years six months, were treated between January 1990 and December 2001. The collar and cuff immobilization technique was used for sixteen children (including four who underwent open revision for early secondary displacement), percutaneous pinning for two, and open crossed pinning for thirty (including four who developed secondary displacement after collar and cuff immobilization). One out of two collar and cuff treatments was instituted within six hours of injury. The four secondary displacements after collar and cuff immobilization treatment occurred after fracture reduction more than six hours after injury. The proportion of open reductions increased with longer delay to reduction after injury. Mean immobilization was three and a half weeks. The Flynn criteria were used to assess outcome at mean seven years eight months follow-up. RESULTS: Outcome was satisfactory in all children treated with definitive collar and cuff immobilization and by percutaneous pinning; the rate was 97% after open procedures (persistent sequelae of radial palsy in one child). DISCUSSION: Early treatment before six hours increased the chances of success with the collar and cuff method which remains the technique of choice for Lagrange and Rigault stage IV extension type supracondylar fractures. In the event of failure or complications, other classical methods should be discussed, including percutaneous pinning or direct access for open osteosynthesis.

Interaction of human chorionic gonadotropin and human luteinizing hormone with human thyroid membranes.

In an attempt to identify a possible pathogenetic role for the hCG molecule in the mechanism of the hyperthyroidism which occurs in choriocarcinoma, we have looked for evidence that the hCG molecule has a thyrotropic action on the human thyroid. The thyrotropic activity of various hCG preparations on the human thyroid was assessed by measuring the stimulation of adenylate cyclase activity in human thyroid plasma membranes purified by sucrose density gradient centrifugation. The highly purified hCG CR119 preparation stimulated human thyroid adenylate cyclase activity. Its activity was more than 654 times greater than could be accounted for by human TSH (hTSH) contamination of the preparation, as determined by RIA. The thyrotropic activity intrinsic to 1.0 IU hCG was equivalent to roughly 0.27 microU hTSH. Significant saturable binding of the 125I-labeled highly purified hCG preparation to human thyroid membranes was demonstrated, and the bound component was characterized. Its apparent molecular size, subunit composition, and testis receptor-binding characteristics were those of the hCG molecule. Examination of a crude urinary hCG preparation in adenylate cyclase and TSH radioligand assays using human thyroid membranes showed no evidence of any molecule other than hCG with a thyrotropic action on the human thyroid. Given that hCG binds to and stimulates adenylate cyclase activity in human thyroid tissue, as the above data indicate, then human LH (hLH) would be expected to do the same, since hLH and hCG have such strong structural and functional similarities. As anticipated, a highly purified hLH preparation exhibited TSH binding inhibition and adenylate cyclase stimulation. Its activity was more than 1030 times greater than could be accounted for by hTSH contamination of the preparation. The thyrotropic activity intrinsic to 1.0 IU hLH was equivalent to roughly 44 microU hTSH. Thus, in addition to other shared properties, the hLH molecule and the hCG molecule share the ability to interact with human thyroid tissue. These results strongly indicate that the hCG molecule has a thyrotropic action on the human thyroid and support the hypothesis that hCG is the thyrotropic factor that mediates the hyperthyroidism which occurs in patients with hCG-secreting neoplasms.

Renal metabolism of the beta-subunit of human choriogonadotropin in the rat.

We analyzed the immunoreactive renal metabolites of the beta-subunit moieties of unlabeled highly purified hCG, hCG beta, and desialylated hCG (as-hCG) in rats by RIA and Sephadex G-100 chromatography. Infusions of hCG beta, as-hCG, or intact hCG resulted in accumulation in the kidney of a large quantity of small mol wt peptides lacking the immunological determinants of the carboxy-terminal peptide (CTP) of the beta-subunit. In the case of as-hCG, renal accumulation of these beta-core fragments was greatly enhanced when as-hCG binding to hepatic galactose receptors was inhibited by infusion of as-fetuin. The beta-core fragments in kidney had the same immunological and G-100 chromatographic characteristics as beta-core fragments in liver, suggesting similar intracellular catabolic mechanisms in these tissues. The kinetics of beta-core fragment turnover in kidney were studied after injection of hCG beta, which is cleared from the circulation within 1 h. Loss of beta CTP immunoreactivity was the initial event in hCB beta catabolism by the kidney; most of this process occurred between 7 and 30 min after injection. This was followed by a gradual reduction of the size of accumulated hCG beta metabolites over the next 60 min. The beta-core fragments that accumulated had a Kav of approximately 0.57 and a very slow degradation rate over the next 5 h (half-life greater than 6 h). Chromatographic analysis of urine obtained 6 h after beginning a continuous infusion of hCG, hCG beta, or as-hCG displayed in each case a major peak corresponding to the infused molecule, apparently intact, and a minor peak of beta CTP immunoreactivity of small mol wt. Relative to the beta CTP fragments apparent in urine, there were few beta-core fragments. These data indicate that separate fates exist for immunoreactive fragments generated by hCG beta metabolism in the rat kidney. One appears to be intracellular and similar to the liver pathway of as-hCG degradation in that it leads to the formation of long-lived beta-core fragments. The other takes place within ready access to the urinary compartment and leads to the accumulation in urine of beta-CTP fragments.

Relevance of the low and high affinity thyrotropin-binding sites of human thyroid membranes to the stimulation of adenylate cyclase.

TSH is known to interact on thyroid membranes with two classes of binding sites that differ in affinity and capacity. To assess the relevance of the class of TSH-binding sites characterized by low affinity and high capacity to the stimulation of adenylate cyclase, we studied the interactions of desialylated hCG (as-hCG) and its beta-subunit (as-hCG beta) with human thyroid membranes. In low ionic strength buffer, pH 7.8, where both classes of sites are operant, as-hCG fully inhibited and as-hCG beta partially inhibited [125I] bovine (b) TSH binding. Scatchard analysis of the [125I]bTSH binding inhibition curve in the presence of 1.0 X 10(-5) M as-hCG beta clearly indicated that as-hCG beta interacted only with the low affinity class of binding sites, leaving the high affinity class unaffected. In the presence of 140 mM NaCl, [125I]bTSH interacted predominantly with the high affinity class of binding sites; as-hCG fully inhibited [125I]bTSH binding to this class of sites, whereas as-hCG beta displayed essentially no interaction. Scatchard analysis of [125I]as-hCG beta binding to human thyroid membranes in low ionic strength buffer revealed a single apparent class of sites with low affinity (Kd = approximately 1.0 X 10(-6) M) and high capacity (Q = approximately 300 pmol/mg membrane protein). The bTSH preparation (Thytropar) showed a 10-fold greater binding inhibition potency at these sites than either the as-hCG or the as-hCG beta preparation, in keeping with the inference that as-hCG beta interacts with the low affinity class of TSH-binding sites. At a concentration more than 3 times that necessary to inhibit TSH binding to the low affinity class of sites, the as-hCG beta molecule neither stimulated adenylate cyclase nor inhibited the ability of TSH to do so. In contrast, the as-hCG molecule, which interacts with both classes of TSH-binding sites, fully inhibited TSH stimulation of adenylate cyclase. We conclude that the low affinity class of TSH-binding sites is not the class of sites through which TSH stimulates adenylate cyclase, and that this role is best ascribed to the high affinity class of TSH-binding sites.

Evidence that desialylation and uptake by hepatic receptors for galactose-terminated glycoproteins are immaterial to the metabolism of human choriogonadotropin in the rat.

It is widely known that removal of sialic acid from the carbohydrate chains of glycoproteins in vitro drastically reduces their survival time in the circulation; however, it is not known whether desialylation plays a significant role in the metabolism of sialylated serum glycoproteins in vivo. We have studied the metabolism of hCG and desialylated hCG (as-hCG) in rat serum and liver in vivo to assess this putative metabolic pathway for glycoprotein hormones. A single injection of as-hCG into rats was followed by its rapid removal from the circulation, principally by the liver, and its degradation into fragments of the hCG beta-subunit that lacked the carboxy-terminal peptide antigenic determinant. Continuous infusion of desialylated fetuin (as-fetuin) at a high rate along with as-hCG dramatically reduced accumulation of the beta-subunit fragments in liver and resulted in increased serum levels of as-hCG. Consequently, the MCR of as-hCG was reduced from 301 +/- 10.3 ml/h (mean +/- SE) to 13.4 +/- 1.15 ml/h by infusion of as-fetuin, which is known to compete for hepatic receptors for galactose-terminated glycoproteins. In contrast, coinfusion of as-fetuin with hCG did not influence the MCR of hCG. Furthermore, there was no serum accumulation of hCG desialylated in its hCG beta carboxy-terminal portion, with or without as-fetuin, and the quantity and pattern of immunoreactive hCG products in liver homogenate were not affected by coinfusion of as-fetuin with hCG. Thus, blockade of hepatic receptors for galactose-terminated glycoproteins did not impede hCG turnover in the circulation, impair hepatic catabolism of hCG, or lead to the accumulation of desialylated products of hCG in plasma. These data indicate that in the rat, there is negligible catabolism of glycoproteins, such as hCG, by a pathway that involves peripheral desialylation and subsequent hepatic uptake via receptors for galactose-terminated glycoproteins.

Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma.

Since thallium-201 imaging has been reported as a potential means of follow-up of patients with differentiated thyroid carcinoma (DTC) during ongoing thyroid suppression therapy, the authors evaluated the diagnostic sensitivity of this procedure in 31 patients known to have metastases or local recurrence. Among 51 tumor sites 201TI imaging had a detection rate of 45% whereas 84% was noted for imaging with 131I administered in therapeutic doses. Thus, even though the effectiveness of the two radionuclides is not strictly comparable due to the difference in the administered doses, Thallium imaging cannot be recommended as the only modality for the follow-up of patients with DTC. Six of the eight tumor sites negative with 131I were positive with 201TI (especially metastatic cervico-mediastinal lymph nodes). So 201TI imaging may particularly be helpful in localizing metastases or recurrences in patients with a negative 131I scan and abnormal levels of serum thyroglobulin.

Rapid in situ detection of chromosome 21 by PRINS technique.

The "PRimed IN Situ labeling" (PRINS) method is an interesting alternative to in situ hybridization for chromosomal detection. In this procedure, chromosome labeling is performed by in situ annealing of specific oligonucleotide primers, followed by primer elongation by a Taq polymerase in the presence of labeled nucleotides. Using this process, we have developed a simple and semi-automatic method for rapid in situ detection of human chromosome 21. The reaction was performed on a programmable temperature cycler, with a chromosome 21 specific oligonucleotide primer. Different samples of normal and trisomic lymphocytes and amniotic fluid cells were used for testing the method. Specific labeling of chromosome 21 was obtained in both metaphases and interphase nuclei in a 1 hour reaction. The use of oligonucleotide primer for in situ labeling overcomes the need for complex preparations of specific DNA probes. The present results demonstrate that PRINS may be a simple and reliable technique for rapidly detecting aneuploidies.

Aneuploidy detection in human sperm nuclei using PRINS technique.

Rapid and specific identification of chromosomes can be attained in situ using the PRimed IN Situ (PRINS) labelling technique. We have adapted this technique to mature human sperm in combination with a protocol for simultaneous decondensation and denaturation of sperm nuclei. This strategy allowed us to obtain double labelling of human spermatozoa in a < 2-hr reaction. In the present study, we report the estimates of disomy for chromosomes 3, 7, 10, 11, and 17 on 64,642 spermatozoa from 2 normal males. The incidences of disomy ranged from 0.28-0.34%. There were no significant interindividual or interchromosomal differences in disomy rates.

Molecular studies of translocations and trisomy involving chromosome 13.

Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13) (p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy: one de novo rob(13q14q), one paternally derived rob(13q14q), two de novo t(13q13q), and one mosaic de novo t(13q13q)/r(13). The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy.

Preimplantation embryo chromosome analysis by primed in situ labeling method.

OBJECTIVE: To present the use of primed in situ labeling method in preimplantation diagnosis. DESIGN: Double- and triple-primed in situ labeling were performed on 10 morphologically abnormal preimplantation embryos, using combinations of specific primers for chromosomes 9, 13, 16, 18, 21, X, and Y. SETTING: Embryos were obtained from patients at the Montpellier University Hospital. PATIENT(S): Seven women undergoing IVF at the Montpellier University Hospital. INTERVENTION(S): Isolated interphase nuclei from poor quality preimplantation embryos were prepared for primed in situ labeling technique. MAIN OUTCOME MEASURE(S): Numerical abnormalities assessed by primed in situ labeling analysis. RESULT(S): Using directly fluorescent-labeled nucleotides, the labeling reaction for three chromosomes did not exceed 2.30 hours. Only three analyzed embryos appeared to be chromosomally normal. Mosaicism, aneupoidy, and haploidy were observed in the seven other embryos. CONCLUSION(S): The primed in situ labeling method offers a simple and reliable screening tool for gender determination and aneuploidy detection. The use of this technique may contribute to significantly improve the procedure of preimplantation diagnosis.

Neurological presentation of three patients with 22q11 deletion (CATCH 22 syndrome).

Chromosome 22q11 deletion (CATCH 22 syndrome or velocardiofacial syndrome) is one of the most frequent chromosomal syndromes. Neurological features other than cognitive disorders are probably the least-described part of the expanding phenotype of the 22q11 deletion. We report the neurological features of three unrelated children with a de novo deletion: one patient with an autistic disorder, a second patient with hypocalcaemic neonatal seizures and unusual persistent epileptic focus at electroencephalographic follow-up, and a third patient with atypical absence epilepsy. These observations enlarge the clinical and neurological spectrum of the 22q11 deletion. Awareness of such cases is necessary, and a diagnosis of the 22q11 deletion should be suspected in children with common neurological features associated with severe or mild dysmorphism. Diagnosis of the 22q11 deletion should be confirmed by fluorescence in situ hybridization analysis associated with standard chromosomal analysis.