Chromosome Complement: A Fertile Hybrid between Equus priewalskii and Equus caballus.

At the Zoological Garden of Antwerp it has been proved that when Equus prjewalskii is crossed with E. caballus the offspring is fertile. As expected, its diploid chromosome number is 65. The morphological differences between the parental and the offspring karyotypes are not great; therefore, meiosis in the hybrid was successfully achieved.

Major decrease in the incidence of trisomy 21 at birth in south Belgium: mass impact of triple test?

In South Belgium (Wallonia), the 'triple test' was introduced in 1990-1991, and is nowadays a widely accepted screening method for assessment of trisomy 21 risk in pregnancy. The 'triple test' is not regulated and can be freely performed by any biomedical lab, making epidemiological data unavailable. By contrast, cytogenetic investigations are limited to a few genetic centres, and accurate statistics can be easily built from their files. During the period 1984-1989, a total of 244 trisomy 21 (1/876 pregnancies) were diagnosed in the Genetic Centres of Liège and Loverval, 42 (17%) of them prenatally. During the period 1993-1998, 294 trisomy 21 (1/704 pregnancies) were observed, 165 (56%) of which prenatally, and more than 90% of affected pregnancies were terminated. Even after correction for late foetal loss of trisomic foetuses, the difference is highly significant, and corresponds to a theoretical shift in the incidence of trisomy 21 at birth from 1/794 to 1/1606. As no remarkable progress occurred in other non-invasive prenatal screening procedures or general health care policies in Belgium, the most reasonable explanation is the use on a large scale of triple test by pregnant women, and the election of termination for most affected pregnancies.

New oral-acral syndrome with partial agenesis of the maxillary bones.

We report on a woman with congenital defect of the anterior part of the maxillary bone (including absence of incisors and canines) without cleft lip or palate, and ectrodactyly of the feet. This syndrome appears to represent a new entity of unknown cause.

Pseudoaminopterin syndrome.

We report on a boy with a combination of manifestations reminiscent of aminopterin embryopathy: brachyturricephaly with craniosynostosis, poorly mineralised vault, upslanted palpebral fissures, malar hypoplasia, high-arched palate, micrognathia, thick, abnormal auricles, ASD, minor hand anomalies, growth and mental retardation. Three convincing cases of "Aminopterin Syndrome Sine Aminopterin" have been reported (the fourth case possibly having the Juberg-Hayward syndrome). Variability and heterogeneity of cases with apparent aminopterin embryopathy are discussed.

Prenatal diagnosis of a dup(3p) with holoprosencephaly.

The prenatal diagnosis of dup(3p) was made in a female conceptus, the father being a known carrier of a balanced translocation t(3;10)(p21;q26). Interruption of pregnancy at 19 weeks showed a fetus with a holoprosencephaly field defect. Two other cases of dup(3p) have been observed in the same family. The malformations were different in each of the 3 patients, suggesting a considerable degree of variability of dup(3p).

Microcephaly, muscular build, rhizomelia, and cataracts: description of a possible recessive syndrome and some comments on the use of electronic databases in syndromology.

We report on a 7-year-old boy born of consanguineous parents with severe microcephaly (-5 SD) but borderline intelligence, juvenile cataract, muscular build, rhizomelic shortness of limbs predominantly of femora, advanced bone age, and micropenis. This combination of signs appears unique and may represent an undescribed, possibly autosomal recessive MCA syndrome. The use of LDDB and POSSUM in the workup of such "new syndromes" is reviewed. Three search strategies are discussed: single rare sign browsing, best combinatory fit using an array of key words, and combined rare signs scan. Pitfalls in the use of such databases and the some problems raised by inconsistent/ incomplete encoding in those two popular, highly useful syndromology retrieval systems are discussed.

Mental retardation, short stature, almond-shaped eyes, small downturned mouth and coned epiphyses: a new case of Hunter-Fraser syndrome.

A 21-year-old male with mental retardation, short stature, almond-shaped eyes, small downturned mouth, and coned epiphyses is presented. The clinical presentation, as well as the metacarpal phalangeal pattern profile, was similar to the affected members of a family reported by Hunter et al.: (Hunter et al.: J Med Genet 14:430-437, 1977). In addition, many features of our patient resembled Ruvalcaba syndrome. However, skeletal abnormalities were different. A reciprocal translocation was also observed in 3 members of our patient's family.

Campomelic syndrome: manifestations in a 20 week fetus and case history of a 5 year old child.

We report on 2 unusual cases of the campomelic syndrome, the first being a fetus in whom the diagnosis was suspected in the 18th week and confirmed sonographically at 20 weeks. The second case concerns a 5 year old 46, XY girl with an exceptional longevity and a relatively favorable evolution.

Glaucoma-lens ectopia-microspherophakia-stiffness-shortness (GEMSS) syndrome: a dominant disease with manifestations of Weill-Marchesani syndromes.

We report on a syndrome of progressive joint stiffness, glaucoma, and lens dislocation observed in three generations and compare it with two previous records of short stature, lens ectopia, and articular limitation. This family confirms the existence of a dominant Weill-Marchesani-like syndrome. We suggest that it could be related to the Moore-Federman syndrome. We coin the acronym GEMSS syndrome (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) to distinguish this dominant Weill-Marchesani-like syndrome from the classic, recessively inherited syndrome.

Acromelic frontonasal "dysplasia": further delineation of a subtype with brain malformation and polydactyly (Toriello syndrome).

We report on a stillborn boy with frontonasal malformation (Sedano-Jiràsek type D-DeMyer type I), associated with encephalocoele, occipital meningocele and preaxial polydactyly of the feet. This form of frontonasal dysplasia was documented previously in a few other cases with various combinations of postaxial polydactyly, tibial hypoplasia, epibulbar dermoid, occipital encephalocoele, corpus callosum agenesis and Dandy-Walker malformation. Most cases are sporadic.

Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome.

We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. "Cerebro-Acro-Visceral Early lethality multiplex syndrome" is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed.

Restrictive dermopathy, a lethal form of arthrogryposis multiplex with skin and bone dysplasias: three new cases and review of the literature.

Restrictive dermopathy is a rare, lethal autosomal recessive syndrome. We report on 3 unrelated affected stillborn infants of consanguineous parents. Clinical findings include a tight, thin, translucent, taut skin, which tears spontaneously in flexion creases, arthrogryposis multiplex congenita (including the temporomandibular joint), enlarged fontanelles, typical face and dysplasia of clavicles and long bones. Histologic abnormalities include hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibres, and abnormal subcutaneous fat. Fifteen previous cases are reviewed.

Monosomy 11q: report of two familial cases and review of the literature.

We present four children from two families with the typical 11q- phenotype resulting from an unbalanced segregation of a parental translocation. In the first family, the father had a 46,XY,t(5;11)(q24;q23.3) constitution. The father of the three other children had a 46,XY,t(11;17)(q23;p13) translocation. Despite associated partial deletion, three of the children had a typical 11q- phenotype. The fourth one, whose pregnancy was terminated in the second trimester, had a hypoplastic left heart but no other considered gross anomalies. A review of 36 previous cases, including 5 due to translocations (4 familial rearrangements, and 1 of unknown origin) is given with emphasis on the relationships between break-points and phenotype. Undescribed manifestations in our patients include agenesis of corpus callosum adactyly and malrotation of the gut.

Private multiple congenital anomaly syndromes may result from unbalanced subtle translocations: t(2q;4p) explains the Lambotte syndrome.

In 1990, Lambotte syndrome was reported as an apparently autosomal recessive multiple congenital anomaly/mental retardation (MCA/MR) syndrome observed in 4 of 12 sibs from a probably consanguineous mating [Verloes et al., Am J Med Genet 1990; 37:119-123]. Major manifestations included intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, hypertelorism, beaked nose, and extremely severe neurologic impairment, with holoprosencephaly in one instance. After the observation of a further affected child born of one unaffected sister, in situ hybridization analysis and chromosome painting techniques demonstrated a subtle t(2;4)(q37.1; p16.2) translocation in the mother, suggesting a combination of 2q/4p trisomy/monosomy in all of the affected children of the family. Many private sporadic or recurrent MCA/MR syndromes maybe due to similar symmetric translocations, undetectable by conventional banding techniques.

Nosology of lysosomal glycogen storage diseases without in vitro acid maltase deficiency. Delineation of a neonatal form.

We describe a boy with an early lethal hypertrophic vacuolar cardiomyopathy of neonatal onset. Abnormal intra- and extralysosomal glycogen storage disease was demonstrated in heart and skeletal muscles. Glycogen content was twice the normal in muscles and over 3-fold the normal in the heart. In this organ, over 50% of the intracellular space was occupied by glycogen and possibly oligosaccharides, as demonstrated by the quantitative morphometric analysis of electron micrographs. The activity of acid alpha-glucosidase was increased in the heart, skeletal muscles, and liver, but was normal in leukocytes. A review of the 11 previously published pedigrees of lysosomal glycogen storage disease with normal in vitro alpha-glucosidase activity allows the delineation of three clinical entities: juvenile and neonatal pseudo-Pompe diseases and partial Pompe disease. Partial Pompe disease, due to the tissue-specific absence of acid alpha-glucosidase, was observed in a single patient. The most common form is the late-onset pseudo-Pompe disease, which is characterized by severe cardiomyopathy and mild myopathy appearing in the second or third decade, prominent arrhythmia with Wolf-Parkinson-White syndrome, and sometimes mental retardation. Patients reported as suffering from Antopol disease probably belong to this group. Dominant inheritance (autosomal or X linked) is likely in most families. The present report appears to be the first one to describe a rapidly fatal neonatal form of lysosomal glycogenosis without acid maltase deficiency. The mode of inheritance of this form is not known. Differential diagosis includes Pompe disease (similar histology) and cardiac phosphorylase b kinase deficiency (similar clinical course). The delineation of neonatal pseudo-Pompe disease makes enzymatic confirmation mandatory in each case suspected of Pompe disease.

Inv(12)(q15q24): a nonrandom change associated with myelodysplasia?

A patient with refractory anemia and a paracentric inversion of chromosome 12, inv(12)(q15q24), is described. This is the second reported case with this chromosome anomaly, suggesting that this rearrangement is a rare but nonrandom change associated with myelodysplastic syndromes.

Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis.

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis.

Nuclear lesions during rat hepatocarcinogenesis. I. Measuring the sister-chromatid exchanges during initiation, promotion and progression of rat hepatocarcinogenesis induced with diethylnitrosamine.

Cytogenetic endpoints such as sister-chromatid exchanges (SCEs), chromosomal aberrations and micronuclei (MNs) have been widely used as indicators of genetic damage. However, no systematic attempts have been made to correlate the levels of these cytogenetic endpoints with the different steps of carcinogenesis. In the present report, the induction, accumulation and persistence of SCEs and high frequency cells (HFCs) were measured in liver cells during the initiation, promotion and progression steps of rat hepatocarcinogenesis induced by diethylnitrosamine (DEN). The results indicate that lesions leading to SCEs accumulate during initiation only. When DEN administration is longer than the duration of this first step, SCE values stabilize. After stopping the carcinogenic treatment, the SCE levels decrease to control values whether or not promotion and progression occur.

Nuclear lesions during rat hepatocarcinogenesis. II. Measuring the micronuclei during initiation, promotion and progression of rat hepatocarcinogenesis induced with diethylnitrosamine.

We reported in our companion paper the strong correlation between elevated sister-chromatid exchange (SCE) frequencies and the initiation step of rat hepatocarcinogenesis. We have also shown that SCEs return to normal values during the promotion and the progression stages. In the present study, we evaluated the clastogenic activity of diethylnitrosamine (DEN) during initiation, promotion and progression of rat hepatocarcinogenesis. We measured, at various times after DEN administration, the number of micronuclei (MN) produced by the mitotic response to partial hepatectomy. The results established that the DEN treatment induces a great number of preclastogenic lesions. In subcarcinogenic conditions (initiation alone), the number of MN expressed after partial hepatectomy remains high regardless of the time interval between the end of the DEN treatment and the operation. In this condition, the preclastogenic lesions persist for up to 1 year after the DEN administration is discontinued. Conversely, in carcinogenic conditions (initiation + promotion + progression), the number of MN expressed after partial hepatectomy decreases during the promotion and progression stages. These observations indicate that promotion and progression but not initiation are associated with the expression of persistent preclastogenic lesions, resulting in the production of chromosomally abnormal hepatocytes.

Cytogenetic study of bovine oocytes matured in vitro.

Described in the present paper is a cytogenetic study of bovine oocytes matured in vitro. The cumulus-oocyte complexes (COC), punctured from ovaries recovered in a local slaughterhouse, were classified into 3 groups according to follicular diameter 1 to 4mm, 5 to 8mm and 9 to 13 mm. Metaphases available for observation were classified as metaphase I, haploid and diploid metaphase II. High levels of haploid metaphases II (90.6, 86.9 and 94.4 %) among the 3 groups of follicular sizes indicated successful meiotic resumption during in vitro maturation and suggested that cytoplasmic maturation may be responsible for low developmental rate after IVM, IVF and in vitro development (IVD).