Wolf–Hirschhorn syndrome (WHS) is a rare chromosomal disorder attributable to a deletion at the short arm of chromosome 4. This syndrome is associated with characteristic facial appearance, multiple congenital abnormalities, mental retardation, feeding difficulties and failure to thrive. We report two girls with WHS who developed myelodysplastic syndrome (MDS). According to the “Category, Cytology, Cytogenetic (CCC)”classification of childhood MDS, patient 1 had refractory cytopenia with ring sideroblasts at the age of 6 years, while patient 2 had refractory cytopenia with dysplasia at the age of 5½ years. Patient 1 progressed to refractory cytopenia with excess blasts within a year, while patient 2 progressed to acute lymphoblastic leukemia within 1 month of presentation. It is possible that allelic loss of a tumor suppressor gene such as WHSC1 and/or FGFR3 from the deleted segment 4p16.3 plays a critical role in the process of malignant transformation. To our knowledge, this is the first report of severe hematological complications like MDS and leukemia in children with WHS and may be an important genetic model for understanding malignant hematological transformation. This report also underscores the importance of evaluating children with WHS for hematopoietic dysfunction. © 2003 Wiley‐Liss, Inc.

Ring chromosome 22 has been described in over 50 cases. A characteristic phenotype has not been fully delineated; however, long face, thick eyebrows, 2-3 toe syndactyly, mental retardation, adequate somatic growth and the absence of major malformations are noted in many cases. An 11-year-old boy with ring chromosome 22 and 46,XY,r(22)(p11.31-q13.31 approximately q13.33) karyotype presented with global developmental delay, autistic disorder, and dolichocephaly, apparently low-set and large ears, midface hypoplasia, and 2-3 toe syndactyly. This is the second report of a ring chromosome 22 with autistic disorder. There appears to be an association between abnormalities of chromosome 22, including r(22), and autistic disorder; however, this occurrence may be a result of the association of autistic disorder with mental retardation rather than specifically due to r(22). The physical findings in this case also suggest that ring chromosome 22 causes a subtle but distinct phenotype which has previously been proposed.

We report on a newborn infant with a de novo triplication of the distal segment of 5p: 46,XX,trp(5) (pter-->p14::p14-->p15.33::p15.33--> qter) and multiple congenital anomalies consistent with triplication of 5p. Partial triplication was documented by fluorescence in situ hybridization with a cosmid probe specific for 5p15.2 and microdissected probes obtained from "5pter." Partial duplication of the short arm of chromosome 5 is associated with a specific phenotype that appears to be dependent on the chromosomal region duplicated. Duplication of 5p with breakpoints proximal to band p14 is generally associated with distinct craniofacial malformations, cardiac, renal, intestinal, and limb defects, and mental retardation, whereas duplications with breakpoints distal to 5p14 result in a milder phenotype characterized by minor facial anomalies, developmental delay, and seizures. The most proximal breakpoints of the partial triplication in this patient was estimated to be 5p14, suggesting that a more severe phenotype can occur with triplication of the more distal segment.

We report on 2 patients with de novo proximal interstitial deletions of the long arm of chromosomes 4: in one the deletion resulted in monosomy (4)(q21.3q23), in the other it produced monosomy (4)(q13.2q23). Review of 9 cases of deletions involving the 4q21/4q22 region reported previously detected a characteristic phenotype in 8 patients. This phenotype was present in our patients. We conclude that the deletion in the 4q21/4q22 region results in a specific clinical syndrome associated with central nervous system overgrowth that may be a result of anomalous imprinting in the 4q21/4q22 region.

Tissue-specific variation in (CGG)n repeat size and methylation status of the FMR1 gene was investigated in 17 female premutation carriers. Minor variation in premutation repeat size among leukocyte, lymphoblast, and fibroblast tissues was noted in some subjects. One subject exhibited a premutation size allele of (CGG)64 in leukocyte and fibroblast tissues by polymerase chain reaction analysis but a normal-size allele of (CGG)46 in lymphoblast cells, suggesting low-level mosaicism in blood and clonality of the lymphoblast cell line. Six subjects exhibited differences in methylation pattern between leukocytes and lymphoblasts but not between leukocytes and fibroblasts, whereas 2 subjects showed large differences in methylation pattern between leukocytes and fibroblasts. Cognitive function was studied in 14 subjects using the Wechsler Adult Intelligence Scale—Revised. Mean Verbal and Performance IQs were well within the average range as was the mean Full Scale IQ; nevertheless, a trend toward lower Performance IQ compared with Verbal IQ was observed. No significant correlation was apparent between Full Scale IQ and (CGG)n repeat size; however, a significant positive correlation was observed between Full Scale IQ and the proportion of the active X carrying the normal FMR1 allele in fibroblasts but not in leukocytes or lymphoblasts. © 1996 Wiley-Liss, Inc.

We report on a terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27-->qter)] in a female newborn infant who died 45 hours after delivery and had multiple congenital abnormalities including bilateral anophthalmia, congenital heart disease, and abnormal genitalia. The findings are compared to those of four previously reported cases with terminal del (3q).

We report on two boys and a girl with interstitial deletion in the short arm of chromosome 4 including the segment p15.2p15.33. All had normal growth with psychomotor retardation, multiple minor congenital anomalies, and a characteristic face distinct from that of the Wolf-Hirschhorn syndrome. One of the patients had congenitally enlarged penis. These patients resemble some of the previously reported patients with similar cytogenetic abnormalities and suggests the recognition of a specific clinical chromosome deletion syndrome.

We report the clinical findings in a boy with mosaicism for a duplication of chromosome 12q13.1 --> q24.2. His clinical characteristics are very similar to previously reported mosaic duplications of the distal long arm of 12, as well as several cases with non-mosaic duplications. It is proposed that this represents a clinically distinguishable syndrome for 12q duplication, in mosaic or non-mosaic form.

Prenatal DiagnosisVolume 12, Issue 5 p. 439-441 Article Annex 5: List of all cytogenetic abnormalities detected D. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorI. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorV. D. Markovic, V. D. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this author D. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorI. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorV. D. Markovic, V. D. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this author First published: May 1992 https://doi.org/10.1002/pd.1970120513Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume12, Issue5Special Issue: Collaborative Studies on Chorion Villus Sampling in North AmericaMay 1992Pages 439-441 RelatedInformation

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Parental chromosomes are usually not analyzed in cases of trisomy 18 because the extra 18 is assumed to have arisen through a meiotic nondisjunctional event. We report on a case of a trisomy 18 and a maternal translocation (2;18)(q34;q12).

Prenatal DiagnosisVolume 12, Issue 5 p. 443-466 Article Annex 6: Chromosome mosaicism in CVS and amniocentesis samples I. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorV. Markovic, V. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this authorD. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this author I. E. Teshima, I. E. Teshima University of Toronto, Ontario, CanadaSearch for more papers by this authorD. K. Kalousek, D. K. Kalousek University of British Columbia, Vancouver, CanadaSearch for more papers by this authorM. J. J. Vekemans, M. J. J. Vekemans McGill University, Montreal, Quebec, CanadaSearch for more papers by this authorV. Markovic, V. Markovic Surrey Place Centre, Toronto, Ontario, CanadaSearch for more papers by this authorD. M. Cox, D. M. Cox University of Calgary, Alberta, CanadaSearch for more papers by this authorL. Dallaire, L. Dallaire University of Montreal, Quebec, CanadaSearch for more papers by this authorR. Gagne, R. Gagne Laval University, Quebec City, Quebec, CanadaSearch for more papers by this authorJ. C. C. Lin, J. C. C. Lin University of Alberta, Edmonton, CanadaSearch for more papers by this authorM. Ray, M. Ray University of Manitoba, Winnipeg, CanadaSearch for more papers by this authorF. R. Sergovich, F. R. Sergovich University of Western Ontario, London, Ontario, CanadaSearch for more papers by this authorI. A. Uchida, I. A. Uchida McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this authorH. Wang, H. Wang University of Ottawa, Ontario, CanadaSearch for more papers by this authorD. J. Tomkins, D. J. Tomkins McMaster University, Hamilton, Ontario, CanadaSearch for more papers by this author First published: May 1992 https://doi.org/10.1002/pd.1970120514Citations: 44AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Bartels, I., Hansmann, I., Holland, U., Zoll, B., Rauskolb, R. (1989). Down syndrome at birth not detected by first-trimester chorionic villus sampling, Am. J. Med. Genet., 34, 606–607. Benn, P. A., Hsu, L. Y. F. (1983). Maternal cell contamination of amniotic fluid cell cultures: results of a U.S. nationwide survey, Am. J. Med. Genet, 15, 297–305. Blakemore, K. J., Watson, M. S., Samuelson, J., Breg, W. R., Mahoney, M. J. (1984). A method for processing first-trimester chorionic villous biopsies for cytogenetic analysis, Am. J. Hum. jenet., 36, 1386–1393. Blakemore, K. J., Samuelson, J., Breg, W. R., Mahoney, M. J. (1985). Maternal metaphases on direct chromosome preparation of first trimester decidua, Hum. Genet., 69, 380. Callan, D. F., Korban, G., Dawson, G., Gugasyan, L., Krumins, E. J. M., Eichenbaum, S., Petrass, J., Purvis-Smith, S., Smith, A., Den Dulk, G., Martin, N. (1988). Extra embryonic/fetal karyotypic discordance during diagnostic chorionic villus sampling, Prenat. Diagn., 8, 453–460. Canadian Collaborative CVS-Amniocenetesis Clinical Trial Group (1989). Multicentre randomised clinical trial of chorion villus sampling and amniocentesis: first report, Lancet, 1, 1–6. Crane, J. P., Cheung, S. W. (1988). An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue, Prenat, Diagn., 8, 119–129. Hogge, W. A., Schonberg, S. A., Golbus, M. S. (1986). Chorionic villus sampling: experience of the first 1000 cases, Am. J. Obstet. Gynecol., 154, 1249–1252. Hsu, L. F., Kaffe, S., Perlis, T. E. (1987). Trisomy 20 mosaicism in prenatal diagnosis–a review and update, Prenat. Diagn., 7, 581–596. Jackson, L., Wapner, R., Barr, M., Hux, C., Davis, G. (1985). Maternal contamination of chorionic villus samples: comparison between direct preparation and culture, Am. J. Hum. Genet., 37 (Suppl.), A99. Jensen, P. K. A., Hertz, J. M., Therkelsen, A. J. (1986). Admixture of maternal metaphases in first trimester direct chromosome preparations?, Prenat. Diagn., 6, 383–385. Kalousek, D. K. (1988). The role of confined chromosomal mosaicism in placental function and human development, Growth, Genet. Hormones, 4, 1–3. Kalousek, D., Dill, F. (1983). Chromosomal mosaicism confined to the placenta in human conceptions, Science, 221, 665–667. Kalousek, D. K., Dill, F. J., Pantzer, T., McGillivray, B., Yong, S. L., Wilson, R. D. (1987). Confined chorionic mosaicism in prenatal diagnosis, Hum. Genet., 77, 163–167. Ledbetter, D. H., Martin, A. O., Verlinsky, Y., Pergament, E., Jackson, L., Yang-Feng, T., Schonberg, S. A., Gilbert, F., Zachary, J. M., Barr, M., Copeland, K. L., DiMaio, M. S., Fine, B., Rosinsky, B., Schuette, J., de la Cruz, F. F., Desnick, R. J., Elias, S., Golbus, M. S., Goldberg, J. D., Lubs, H. A., Mahoney, M. J., Rhoads, G. G., Simpson, J. L., Schlesselman, S. E. (1990). Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study, Am. J. Obstet. Gynecol., 162, 495–501. Martin, A. O., Elias, S., Rosinsky, B., Bombard, A. T., Simpson, J. L. (1986). False-negative finding on chorionic villus sampling, Lancet, 2, 391–392. Reddy, K. S., Peterson, M. B., Corson, V., Escallon, C., Antonarakis, S. E., Blakemore, K. J. (1990). The vanishing twin: an explanation for discordance between CVS karyotype and fetal phenotype using chromosome markers and DNA studies, Am. J. Hum. Genet., 47 (Suppl.), A284. Simoni, G., Brambati, B., Danesino, C., Rossella, F., Terzoli, G. L., Ferrari, M., Fraccaro, M. (1983). Efficient direct chromosome analyses and enzyme determinations from chorionic villi samples in the first trimester of pregnancy, Hum. Genet., 63, 349–357. Tharapel, A. T., Elias, S., Shulman, L. P., Seely, L., Emerson, D. S., Simpson, J. L. (1989). Resorbed co-twin as an explanation for discrepant chorionic villus results: non-mosaic 47,XX,+16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal blood, Prenat. Diagn., 9, 467–472. Vejerslev, L. O., Mikkelsen, M. (1989). The European collaborative study on mosaicism in chorionic villus sampling: data from 1986 to 1987, Prenat. Diagn., 9, 575–588. Vekemans, M. J. J., Perry, T. B. (1986). Cytogenetic analysis of chorionic villi: a technical assessment, Hum. Genet., 72, 307–310. Williams, J., Medearis, A. L., Chu, W. H., Kovacs, G. D., Kaback, M. M. (1987). Maternal cell contamination in cultured chorionic villi: comparison of chromosome Q-polymorphisms derived from villi, fetal skin and maternal lymphocytes, Prenat. Diagn., 7, 315–322. Wirtz, A., Seidel, H., Brusis, E., Murken, J. (1988). Another false-negative finding on placental sampling, Prenat. Diagn., 8, 321. Worton, R. G., Stern, R. (1984). A Canadian collaborative study of mosaicism in amniotic fluid cell cultures, Prenat. Diagn., 4, 131–144. Citing Literature Volume12, Issue5Special Issue: Collaborative Studies on Chorion Villus Sampling in North AmericaMay 1992Pages 443-466 ReferencesRelatedInformation

We report on an infant with multiple congenital anomalies including complex craniosynostosis associated with an unbalanced karyotype, 46,XY,-2,+der(2),t(2;15)(q37;q26)pat. The previous report of a child with cloverleaf skull and partial duplication of 15q25----qter and the Man-on-Mouse Homology map suggests that a critical segment for synostosis of sutures may be in this region.