De novo highly complex chromosome rearrangement (CCR) involving five breakpoints with congenital anomalies analyzed by FISH.

We report on a child with ptosis, epicanthal folds, depressed nasal bridge, carp-shaped mouth, low set ears, hirsutism, pectus excavatum, and developmental and language delay presenting with a balanced complex chromosomal rearrangement (CCR). R- and G-banding methods and fluorescence in situ hybridization were used to document that this is a complex translocation with five breakpoints involving chromosomes 1, 7, 10 and 21.     

De novo complex chromosome rearrangement: a study of two patients

Complex chromosome rearrangements (CCR) involving multiple breaks in two or more chromosomes are rare. We describe a girl with development delay and overgrowth who presents a nine-break apparently balanced de novo rearrangement involving chromosomes 1, 2, 3, 4 and 12, and a boy with developmental delay and seizures with a complex three-chromosome apparently balanced de novo rearrangement involving chromosomes 2, 7 and 13. The relationship between clinical abnormalities and apparently balanced rearrangements is discussed.     

Renal urologic anomalies presenting in adult identical twins

Two sets of identical adult twins recently presented to our hospital. In one case, the patients demonstrated (ipsilateral) renal agenesis. In the other, the patients presented approximately one year apart with symptomatic (ipsilateral) ureteropelvic junction obstructions. Although the literature suggests a few reports of this type in the pediatric and newborn population, the authors are unaware of similar reports in adults.     

De novo balanced complex chromosome rearrangement (CCR) involving chromosome 8, 11 and 16 in a boy with mild developmental delay and psychotic disorder

Congenital Complex Chromosome rearrangements (CCRs) compatible with life are rare in humans. We report a de novo CCR involving chromosomes 8, 11 and 16 with 4 breakpoints in a patient with mild dysmorphic features, acquisition delay and psychotic disorder. Conventional cytogenetic analysis revealed an apparently balanced 8;16 translocation. Further FISH analysis with WCP 8 and WCP 16 probes revealed the presence of a third chromosome involved in the translocation. The multicolour karyotype confirmed the complexity of the rearrangement and showed that the derivative chromosome 8 was composed of 3 distinct segments derived from chromosomes 8, 16 and 11. The breakpoints of this complex rearrangement were located at 8q21, 11q14, 11q23 and 16q12. Comparative genomic hybridization (CGH) and array-CGH were performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No imbalance was detected by these two techniques. Our study showed: i) the necessity to confirm reciprocal translocations with FISH using painting probes, particularly when the karyotype resolution is weak; ii) the usefulness of multicolour karyotype for the characterization of structural chromosomal rearrangements, particularly when they are complex; iii) the usefulness of CGH and array-CGH in cases of abnormal phenotype and apparently balanced rearrangement in order to explore the breakpoints and to detect additional imbalances.     

De novo complex chromosomal rearrangement in a woman with recurrent spontaneous abortion and one healthy daughter

Summary Although rare, complex chromosomal rearrangements have been reported in the literature. The result is multiple congenital malformations in the offspring and recurrent spontaneous abortion. Chromosome 7 is usually involved, but in our patient chromosome 18 was involved.     

Ring chromosome 10 Associated with multiple congenital malformations

Summary A paracentric inversion of the short arm of chromosome 1 (inv(1)(p22p36)) is reported in a deeply mentally retarded 19-year-old girl and in her normal father.     

De novo supernumerary marker chromosome originating from chromosome 17 resulting in a normal pregnancy outcome

We report here a prenatal case with de novo supernumerary marker chromosome originating from chromosome 17 in non-mosaic form resulting in normal pregnancy outcome. In this case, a 26-year-old pregnant woman was referred for amniocenthesis and microdeletion Fluorescence In Situ Hybridization (FISH) testing at 18 weeks of gestation due to history of a previous child with Angelman Syndrome. PWS/AS region deletion was excluded by FISH. A de novo supernumerary, non-satellited, monocentric marker chromosome was detected during conventional cytogenetic analysis. With the use of FISH testing, it was found that the marker chromosome originated from chromosome 17. Additionally, the marker chromosome was found not to contain the Smith-Magenis and Miller Dieker syndrome regions. After detailed review of the literature, genetic counseling was given to the family, and the family decided to continue the pregnancy to term. A female child was born at term without any phenotypical abnormalities and clinical complications. Follow-up at 15 months-of-age revealed no developmental abnormalities. To our knowledge, our patient is the first reported prenatal case with a de novo monocentric, supernumerary marker chromosome derived from chromosome 17 in a non-mosaic form that resulting in normal pregnancy outcome.     

De novo ring chromosome 3 in a girl with hypoplastic thumb and coloboma of iris

We describe a female child with a ring chromosome 3, found after investigation for short stature. Her karyotype was 46,XX,r(3)(p26-q29). Her phenotype mainly differs from that of the nine patients previously reported with ring chromosome 3, by the presence of hypoplastic right thumb and bilateral coloboma of the iris.     

Craniofacial anomalies in twins

Studies of twins provide insight into the relative contribution of genetic and environmental factors in the causality of structural anomalies. Thirty-five affected twin pairs were identified from a group of 1114 patients with congenital craniofacial deformities evaluated from 1972 to 1989. Forty-three of these 70 twins exhibited one or more craniofacial anomalies; these were analyzed for dysmorphic characteristics, zygosity, concordance, and family history. The anomalies were categorized into two groups: malformations and deformations. The malformations (n = 36) included hemifacial microsomia (n = 10), cleft lip and palate (n = 8), cleft palate (n = 4), rare facial cleft (n = 2), craniosynostosis (n = 2), Binder syndrome (n = 2), Treacher Collins syndrome (n = 2), craniopagus (n = 2), CHARGE association (n = 1), frontonasal dysplasia (n = 2), and constricted ears (n = 1). The deformations (n = 7) included plagiocephaly (n = 5), hemifacial hypoplasia (n = 1), and micrognathia (n = 1). Twenty-one monozygotic and 14 dizygotic twin pairs were identified. The concordance rate was 33 percent for monozygotic twins and 7 percent for dizygotic twins.(ABSTRACT TRUNCATED AT 250 WORDS)     

De novo evolution of satellite DNA on the rye B chromosome

The most distinctive region of the rye B chromosome is a subtelomeric domain that contains an exceptional concentration of B-chromosome-specific sequences. At metaphase this domain appears to be the physical counterpart of the subtelomeric heterochromatic regions present on standard rye chromosomes, but its conformation at interphase is less condensed. In this report we show that the two sequence families that have been previously found to make up the bulk of the domain have been assembled from fragments of a variety of sequence elements, giving rise to their ostensibly foreign origin. A single mechanism, probably based on synthesis-dependent strand annealing (SDSA), is responsible for their assembly. We provide evidence for sequential evolution of one family on the B chromosome itself. The extent of these rearrangements and the complexity of the higher-order organization of the B-chromosome-specific families indicate that instability is a property of the domain itself, rather than of any single sequence. Indirect evidence suggests that particular fragments may have been selected to confer different properties on the domain and that rearrangements are frequently selected for their effect on DNA structure. The current organization appears to represent a transient stage in the evolution of a conventional heterochromatic region from complex sequences.     

Cerebellar dysgenesis and mental retardation associated with a complex chromosome rearrangement

Cerebellar hypoplasia, mild mental retardation, skeletal abnormalities, and ataxia were present in a 40 years old patient with a complex chromosome rearrangement (CCR). Chromosomes 2, 5, 16, and 17 were involved in the CCR. For the definition of the eight breakpoints leading to the rearrangement FISH with whole chromosomes paintings and specific telomeric probes was employed. Gene disruption, positional effect variegation, and sub-microscopic deletions are all possible causes for the abnormal phenotype observed in the patient.     

Laurence-Moon-Biedl syndrome in presumably identical twins

Summary A Saudi Arabian family with 3 cases of Laurence-Moon-Biedl syndrome, 2 of whom are presumably identical twins, is presented. Although it is generally accepted that this condition is inherited as an autosomal recessive trait, no conclusive data exist in the literature to support this theory.

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Zusammenfassung Wir präsentieren eine saudiarabische Familie, in der 2 Mitglieder vermutlich eineiige Zwillinge sind. In dieser Familie finden sich 3 Fälle von Laurence-Moon-Biedl-Syndrom. Wenngleich allgemein angenommen wird, daß dieser Zustand als autosomales recessives Merkmal vererbt wird, existieren hierfür keine überzeugenden Daten in der Literatur.

     

Ring 18 mosaicism in identical twins

Summary Male identical twins with r(18)/normal mosaicism are reported. Twin 1 has the characteristic manifestations of the r(18) syndrome, but twin 2 shows a normal phenotype. Cytogenetic study of cultured lymphocytes revealed that the proportions of r(18) are 19.7% and 19.2%, respectively. However in the fibroblast cultures, the ring is observed in 51% of cells in twin 1 and in 0% in twin 2. The mechanism of the occurrence of the discrepant phenotypes in the twins is discussed.     

Parental origin of a ring 13 chromosome in a female with multiple anomalies

Summary A ring chromosome No. 13 was found in a 21-year-old female with multiple anomalies suggestive of 13q-syndrome. Chromosomes of the girl and her parents, studied by quinacrine staining, revealed the ring to be of paternal origin. Detailed study of the quinacrine banding pattern of the ring indicated loss of the most distal band of the long arm (13q34) and possible partial loss of the next adjacent long arm band (13q33). The short arm (13q11) was present but the stalk (13p12) and satellite (13p13) regions appeared to be missing.This work was supported in part by NIH grants HD 07997; Maternal and Child Health Services 970; HD 08236; CA 16747; by grants from the Medical Research Foundation of Oregon and by a Basil O'Connor Starter Research Grant.     

Unique anomalies in cephalothoracopagus janiceps conjoined twins with implications for multiple mechanisms in the abnormal embryogenesis

The anatomic features of female conjoined twins with the Janiceps type of cephalothoracopagus are described. Abnormalities included bilateral clefts of the alveolar arches, shared rudimentary mandible, high, arched clavicles, multiple rib deformities, single shared foregut and small intestine, absent large intestines, omphalocele, multicystic kidneys, hypoplastic lungs, interconnected aortas and neck vessels, single ovary with elongated uterus in each twin, displaced labia, abnormal segmentation of the vertebrae, spinal dysraphism, diastasis of the symphysis pubis, malrotated lower extremity, bilateral posterior dislocation of the hips, and club feet. There were two hearts with internal anomalies. Both spinal cords had a myelocele in the lumbar region. The abnormalities noted in previous reports of conjoined twins of this type are reviewed and compared. We propose that factors associated with conjoining, dysgenetic (developmental) defects, and deformations resulting from crowding in utero all may have been important in the abnormal development in this case.