Further clinical delineation in trisomy 1q32 syndrome.

A male newborn with multiple congenital abnormalities was studied. Clinically, he showed prominent forehead, facial dysmorphism, ear malformations, congenital heart defect and limb anomalies. The cytogenetic studies demonstrated a karyotype 46,XY, der(18) t(1;18)(q32;p11.3)pat with partial trisomy 1q32-qter and a monosomy 18p. The patient displayed clinical features of trisomy 1q but not of monosomy 18p. There are around 80 reports of trisomy 1q32. The purpose of this paper is to describe the first case of a translocation involving 1q and 18p chromosome breakpoints. Additional findings detected in the propositus permit us a further delineation of the trisomy 1q syndrome.     

Partial trisomy 8q and partial monosomy 18p: a case report

We report clinical observations and cytogenetic studies of an inherited partial trisomy 8q and partial monosomy 18p. A full trisomy 8 syndrome (Warkany syndrome) is a clinically recognized syndrome. Partial trisomy 8q has been reported sporadically in the literature with variable phenotypes. Partial monosomy 18p, deletion of the short arm of chromosome 18, is also a well-recognized syndrome. This is the first report to the best of our knowledge of partial trisomy for distal 8q and partial monosomy for distal 18p occurring together in a patient.     

Partial trisomy 17q and monosomy 9p due to a familial translocation.

Described is an infant with partial trisomy 17q and monosomy 9p [46,XX,-9,+der(9)t(9;17)(p21;q23)] due to adjacent-1 segregation of a maternal balanced reciprocal translocation. Characteristic clinical features of both partial 17q trisomy and monosomy 9p are present, but the former syndrome is less recognisable in this infant than in previously reported cases due to the concomitant 9p monosomy.     

Sister chromatid exchanges and chromosome aberrations in fibroblasts from patients with retinoblastoma

Summary The frequencies of sister chromatid exchanges (SCEs) and chromosome breaks were investigated in five diploid fibroblast strains derived from three patients with deletion 13[del(13)] retinoblastoma, one patient with a hereditary form of retinoblastoma, and one trisomy 13. The fibroblasts with del(13)(q14q22) showed slightly increased SCEs (at a P level of 5–10%), but the others, including del(13)(q12q14), the hereditary form of retinoblastoma, and trisomy 13, did not have increased SCEs as compared to normal controls. No increase in chromosome breaks was found in these fibroblasts. The results suggest that retinoblastoma is not associated with spontaneous increased chromosomal instability.     

Duplication 11 (q22----qter) in an infant. A case report with review

A male infant with partial duplication of the long arm of chromosome 11 (11q22----qter) is described with a hitherto unreported translocation. In most cases 11q trisomy is associated with 11q/22q translocation and a 3:1 meiotic disjunction with 47 chromosomes. In a few cases the 11q translocation is associated with a partial deletion of other autosomes and a total of 46 chromosomes. In the present case, translocation to 9p is involved and no apparent deletion of 9p was noted, providing an opportunity to delineate the phenotypic features due to duplication of 11q. A comparison is made between the findings of partial 11q trisomy and 11q/22q translocation.     

Phenotypic and cytogenetic spectrum of 9p trisomy

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.     

Partial trisomy 18q11.2-->qter due to de novo unbalanced translocation of chromosomes 15 and 18 analyzed by fluorescence in situ hybridization

This report presents a case with partial trisomy 18q resulting from de novo unbalanced translocation of chromosomes 15 and 18 displaying the features of pure trisomy. This is the first reported case with partial trisomy 18q due to unbalanced translocation between chromosomes 15 and 18. Clinical findings of our case have been compared with the reported cases' had partial trisomy 18q and the importance to recognize the cases with chromosome abnormalities to give genetic counseling and prenatal diagnosis for subsequent pregnancies has emphasized.     

‘Complete’ trisomy 5p; de novo translocation t(2;5)(q36;p11) with isochromosome 5p

Summary A case of complete trisomy 5p due to a de novo translocation t(2;5)(q36;p11) with an isochromosome 5p is described. Complete trisomy 5p has been reported only once (Brimblecombe et al., 1977). The confusing literature relating to partial trisomy 5p is reviewed. Comparison of our case with the patients reported by Brimblecombe et al. (1977) and by Opitz and Patau (1975) is suggestive for a distinct clinical syndrome if (almost) the complete short arm of chromosome 5 is present in a trisomic state. Unfortunately the clinical findings in the case of Brimblecombe (1966, 1977) are poorly documented. The main features of this syndrome are: macrocephaly, psychomotor retardation, hypotonia, postnatal growth failure, tracheobronchial involvement, mongoloid slant of the eyes, epicanthus, low-set ears, depressed nasal bridge, short first toe, and seizures.     

An unusual clinical characterization of a male with distal partial trisomy 1q42.1 and monosomy 4q35.1 and review of the literature

We report a male patient with a karyotype of 46,XY, der(4)t(1;4)(q42.1;q35.1) inherited from a maternal balanced translocation involving chromosome 1q and 4q. The boy had corpus callosum dysgenesis, laryngomalacia, tracheobronchus, facial dysmorphism, simian creases, and developmental retardation. The first three features are unique compared to previous literature reports on distal partial trisomy 1q. This case report allows a further delineation of the distal partial trisomy 1q syndrome.     

Combined trisomy 9P and Shprintzen syndrome resulting from a paternal t(9;22)

The authors report on a female infant with partial trisomy 9 (pter-->q12) together with partial monosomy 22 (pter-->q11.23) that included DiGeorge critical region (DGCR), as a result of adjacent-2 disjunction. In addition to the clinical features characteristic of trisomy 9p syndrome, the patient had Truncus arteriosus type A2, bilateral hydronephrosis, palatal anomaly, retrognathia, and laryngeal hypotonia, which are likely to be attributed to 22q11.2 deletion. This patient appears to be the first reported case with such unbalanced translocation resulting from a paternal reciprocal translocation. For live birth, the risk for male carrier is 8.7-17.4%. It is important to consider this higher risk when counseling. Precise study concerning the presence of the DGCR can facilitate in the better understanding of the condition.     

Precocious puberty associated with partial trisomy 18q and monosomy 11q

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication 18q but she has also some atypical anomalies such as precocious puberty, a retinal albinism and hypermetropia. Based on cytogenetics and FISH analysis, the karyotype of the proband was 46,XX,der(11)t(11;18)(q24;q13). To the best of our knowledge, this is the first report of precocious puberty associated with either dup(18q) or del(11q) syndromes.     

Prenatal diagnosis of a de novo trisomy case 9q-47,XX,+9 del(q33----qter)

A case of de novo trisomy 9q- (deletion q33----qter) in utero diagnosed is reported. Features of this syndrome are described, compared with those of trisomy 9p et total trisomy 9. The possibility of prenatal diagnosis and the similarity of some features with nail-patella syndrome are focused.     

Trisomy 4q syndrome: presentation of a new case and review of the literature

We describe the 11th case of a de novo partial trisomy of the long arm of chromosome 4, with the extra segment spanning from 4q27 to 4q35. The aberration resulted from an unbalanced translocation of material from 4q to the short arm of chromosome 7, as evident from fluorescent in situ hybridization. Microsatellite analysis revealed the extra material to originate from the father. The karyotype was interpreted as 46,XX,der(7)t(4;7)(q27;p22). The patient is a 13-year-old girl with severe mental retardation, growth retardation, hearing impairment as well as minor foot, thumb and facial anomalies. Although the extent of the aberration varies between the reported patients, there are nevertheless features in common, suggestive of a trisomy 4q syndrome. The clinical findings most frequently reported are: mental retardation, seizures, microcephaly, hearing impairment and growth retardation, as well as epicanthic folds, high/broad/depressed nasal bridge, malformed ears, tooth and thumb anomalies. Almost the entire long arm of chromosome 4, except band q11, has been involved in trisomies/duplications, but 4q27 and 4q31 seem to be preferentially engaged in the trisomy 4q syndrome.     

Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18.

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, we have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. We have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals.     

Two cases of del(13q)-retinoblastoma and two cases of partial trisomy due to a familial insertion

A del(13)(q13q21.1) was found in a patient with bilateral retinoblastoma and mental retardation. The father was carrier of an ins(16;13)(q12.2;q13q21.1) which also was present in several other family members, and responsible for another case of del (13q)-retinoblastoma and two cases of trisomy for the inserted segment. This second del(13q) patient was also carrier of a balanced t(11;22).     

Genetics of partial trisomies. I. Trisomy 2q

The family, where 2 children had partial trisomy 2q33-q ter, due to paternal translocation t(2;18) (q33;p11.1), was examined. The analysis of 36 cases of trisomy 2q showed that the forms connected with parental chromosomal rearrangement prevailed in the genesis of trisomy 2q. Moreover, the balanced carrier-mothers were more common than fathers. The 2q34-q ter segment may be considered "critical" for occurrence of trisomy 2q syndrome. In case of equal triplication, the similarity between the patients within the same family is greater than between those from different families. The value of intragroup similarity between the patients with equal trisomies may be used for evaluation of phenotypical similarity at different triplicated segments.     

M-FISH applications in clinical genetics

Until recently, presence of de novo marker or derivative chromosomes was quite problematic for genetic counseling especially in prenatal diagnosis, because characterization of marker and derivative chromosomes by conventional cytogenetic techniques was nearly impossible. However, recently developed molecular cytogenetic technique named Multicolor Fluorescence in Situ Hybridization (M-FISH) which paints all human chromosomes in 24 different colors allows us to characterize marker and derivative chromosomes in a single hybridization. In this study, we applied M-FISH to determine the origin of 3 marker and 3 derivative chromosomes. Marker chromosomes were found to originate from chromosome 15 in two postnatal and one prenatal case. Of these, one of the postnatal cases displayed clinical findings of inv dup (115) syndrome and the other of infertility, and the prenatal case went through amniocentesis due to the triple test results. Karyotypes of the patients with derivative chromosomes were designated as 46,XY,der (21)t(1;21)(q32;p11), 46,XX,der(8)t(8;9)(p23;p22) and 46,XX,der(18)t(18;20)(q32;p11.2) according to cytogenetic and M-FISH studies. All of the M-FISH results were confirmed with locus specific or whole chromosome painting probes. The case with der (8)t(8;9) had trisomy 9(p22-pter) and monosomy 8(p23-pter) due to this derivative chromosome. The case with der(18)t(18;20) had trisomy 20(p11.2-pter) and monosomy 18(q32-qter). Parental origins of the derivative chromosomes were analyzed using microsatellite markers located in the trisomic chromosomal segments. Patients' clinical findings were compared with the literature.     

A second case of inv(4)pat with both recombinants in the offspring: rec dup(4q) in a girl with Wolf-Hirschhorn syndrome and rec dup(4p)

In a girl presenting with features of Wolf-Hirschhorn syndrome, cytogenetic and molecular cytogenetic analysis revealed a rearranged chromosome 4 with monosomy of the distal bands 4pter-->4p16.2 and trisomy of the distal bands 4q35.1-->4qter [rec dup(4q)] due to a large, paternal pericentric inversion. In the following two pregnancies, prenatal diagnosis showed the same imbalance in one fetus and a reverse segmental imbalance [rec dup(4p)] in the other. We discuss the recombination risk of the given inversion with respect to the size of the inverted segment and the viability of the recombinants. The high frequency of recombinants in this family and others suggests a high recurrence risk in similar cases with large pericentric inversions comprising almost entire chromosomes.     

Partial and complete trisomy 9: Delineation of a trisomy 9 syndrome

Summary Two infants with trisomy involving chromosome 9 are described. One had complete trisomy 9 and the other karyotype 47,XX,+der(9),t(7;9)(p22;q32)mat. A trisomy 9 syndrome is delineated, consisting of features of the trisomy 9p syndrome and various other malformations. These include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death. A possible relationship of some of these findings to regions of 9q involved in cases of partial trisomy 9 is suggested.     

Langer-Giedion syndrome,in a child with complex structural aberration of chromosome 8

A patient with typical features of the Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome, type II) is described. In the karyotype an interstitial deletion of the long arm of chromosome 8 (band 8q22) was observed as the result of a complex rearrangement of chromosomes 1 and 8: 46,XY inv(8)(q23 leads to q242), del(8)(q221 leads to q223), ins(8;1) (q221;p321 p341;q242). Previously reported cases of Langer-Giedion syndrome with deletion of 8q are compared with the present one.