Craniosynostosis associated with partial duplication of 15q and deletion of 2q

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. © 1992 Wiley-Liss, Inc.     

Craniosynostosis associated with partial duplication of 15q and deletion of 2q.

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.     

Partial duplication 4q and deletion 1p36 in monozygotic twins with discordant phenotypes

We report on monozygotic (MZ) twins with a de novo chromosome abnormality consisting of a partial duplication of chromosome 4 (q25-qter) and deletion of chromosome 1p36. These infants had dysmorphic facial features and other clinical manifestations similar to those described with the previously delineated duplication 4q and deletion 1p36 phenotypes and two other reported cases of combined partial duplication 4q and deletion 1p36. However, the twins were discordant for a number of congenital anomalies. The discordant phenotypes described in these genetically identical infants demonstrate that nongenetic factors may play a significant role in the phenotypic differences in patients with recognized chromosome duplication and deletion syndromes, which are usually attributed to the individual genotypic differences in the duplicated and/or deleted chromosome segments.     

Terminal 4q deletion and 8q duplication in a patient with CHARGE-like features

The CHARGE syndrome is a multiple congenital malformation syndrome that usually results from deletion or heterozygous loss of function mutations of the chromodomain helicase DNA-binding protein 7 (CHD7) gene at 8q12.1. Besides CHD7-related cases, some patients with CHARGE-like phenotype have been reported with chromosomal imbalances. We describe a patient with a pattern of malformations reminiscent of CHARGE syndrome: choanal atresia, facial dysmorphism (micrognathia, hypertelorism, epicanthic folds, and depressed, broad nasal bridge), cardiovascular malformations, cryptorchidism, and developmental delay. He had duplication 8q and deletion 4q derived from paternal translocation t(4;8)(q34;q22.1). CHD7 mutation or deletion was excluded. The present report to the best of our knowledge is the only one describing an unbalanced translocation t(4;8) and CHARGE-like phenotype.     

Familial reciprocal translocation, t(2;10)(p24;q26), resulting in duplication 2p and deletion 10q

We describe a familial reciprocal translocation between the distal part of the short arm of chromosome 2 and the long arm of chromosome 10. Five individuals in two generations had multiple congenital anomalies. Their karyotypes were 46, XX or XY,−10, + der(10), t(2;10)(p24;q26). Seven persons were balanced translocation carriers whose karyotypes were 46, XX or XY, t(2;10)(p24;q26). Common manifestations included mental retardation, strabismus, narrow high-arched palate, wide alveolar ridges, other facial abnormalities, genital abnormalities and mutism. The phenotype of the unbalanced individuals is compared to that of previously published cases of the syndrome of partial duplication 2p and to reported patients with partial deletion of 10q.     

Unusual 8p inverted duplication deletion with telomere capture from 8q

Inverted 8p duplication deletions are recurrent chromosomal rearrangements that are mediated through non-allelic homologous recombination (NAHR) between olfactory receptor (OR) gene clusters at 8p23.1. These rearrangements result in a proximal inverted duplication of various extent, a single copy region between the OR gene clusters and a terminal 8p deletion. The terminal deletions are stabilized by direct addition of telomeric repeats, so called telomere healing. Here, we report a patient with an unusual inverted duplication deletion of 8p. Stabilization of the broken chromosome end was achieved by telomere capture instead of telomere healing, resulting in an additional duplication of 8q24.13→qter on the short arm of chromosome 8. Moreover, the inverted duplication was only 3.4 Mb in size (restricted to band 8p22) and thus cytogenetically undetectable. To the best of our knowledge this is the smallest inverted duplication reported hitherto. We describe the molecular characterization by FISH and array CGH of this unusual inv dup del (8p) and a previously reported patient with a similar 8q duplication and review the literature on cases associated with telomere capture.     

DiGeorge anomaly associated with 10p deletion

DiGeorge anomaly (DGA) represents a heterogeneous entity, which is often sporadic, although familial cases and the association with monosomy 22q11 have been reported. Recently, a few patients with 10p deletion syndrome and immunological and other laboratory findings similar to DGA have been described. We report on an additional case of partial DGA associated with 10p deletion.     

Patient with terminal duplication 3q and terminal deletion 5q: comparison with the 3q duplication syndrome and distal 5q deletion syndrome

Partial duplication of chromosome 3q is a well-described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann-de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 --> qter) and terminal deletion of 5q (q35.2 --> qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities.     

A presumptive translocation 1p;2q resulting in duplication 1p and deletion 2q

Here we report on a girl with a translocation between 1 and 2 and duplication 1p and deletion 2q resulting in a multiple congenital anomaly syndrome including intrauterine growth retardation, microcephaly, hypotelorism, cleft palate, subglottic stenosis, umbilical hernia, scoliosis, anal atresia, bilateral calcaneovalgus, overlapping toes, and vertebral anomalies.     

De novo 3q/7q translocation and associated interstitial 7q35 deletion

In the present report we describe a severely mentally retarded and dysmorphic female child with a de novo 3q/7q reciprocal translocation and loss of band 7q35. This finding supports the hyothesis that the occurrence of mental retardation and/or congenital malformations in de novo autosomal reciprocal translocation may be due to the loss of a small amount of chromatin material during this chromosomal rearrangement.     

2q34-qter duplication and 4q34.2-qter deletion in a patient with developmental delay

The 2q3 duplication and 4q3 deletion syndromes are two conditions with variable phenotypes including Pierre-Robin sequence (PRS), limb anomalies, congenital heart defects (CHD), developmental delays and intellectual disabilities. We describe a patient born to a mother with a balanced t(2; 4) translocation who combines both a 2q34-qter duplication and a 4q34.2-qter deletion through inheritance of the derivative chromosome 4 (der(4)). He showed developmental delay, growth retardation, hearing problems, minor facial and non-facial anomalies, such as bilateral fifth finger shortness and clinodactyly, but no PRS or CHD. The comparison of his features with those of 46 and 65 published cases of 2q3 duplication and 4q3 deletion, respectively, allows us to further restrict the size of the proposed critical intervals for PRS and CHD on chromosome 4.     

Unbalanced three-way chromosomal translocation leading to deletion 18q and duplication 20p

In 1980, a case report on a boy with cleft palate, club feet, dysmorphic features, and developmental delay was published by Bijlsma as a possible distinct syndrome. This case is listed in the London Medical Databases version 1.0.We have reevaluated this patient at adult age. Using high resolution karyotyping and Affymetrix 250k SNP array analysis we identified an unbalanced three-way translocation with breakpoints at 17q22, 18q22.1, and 20p12.2 leading to deletion 18q and duplication 20p. Also, a 715 kb duplication in 1p34.2 and a 245 kb deletion at 1p21.1 were found. Mental retardation, cleft palate, and club feet have repeatedly been reported in deletion 18q patients and therefore we conclude that most of the patient’s features can be explained by an 18q deletion.     

Two concurrent chromosomal aberrations involving interstitial deletion in 1q24.2q25.2 and inverted duplication and deletion in 10q26 in a patient with stroke associated with antithrombin deficiency and a patent foramen ovale

Advanced high-throughput molecular cytogenetic analysis has enabled the identification of small chromosomal rearrangements, and two or more concurrently occurring chromosomal rearrangements have been identified using this technique. A girl with severe psychomotor developmental delay associated with an uncertain abnormality (detected by conventional karyotyping) in chromosome 10q had a sudden stroke at the age of 35 months. Laboratory and radiographic examinations revealed antithrombin (AT) deficiency and a patent foramen ovale (PFO). Two concurrent chromosomal aberrations, inverted duplication and deletion in the 10q26 region and a microdeletion in the 1q24.2q25.2 region including the AT gene (SERPINC1), were identified by microarray-based comparative genomic hybridization analysis. Both chromosomal aberrations were found to be of paternal origin. This study described the concurrence of chromosomal rearrangements involving two chromosomes, and estimated the frequency of two or more chromosomal aberrations as 2-4%.     

Case of 15q26-qter deletion associated with a Prader-Willi phenotype

Prader-Willi syndrome (PWS) is one of the common neurogenetic disorders associated with intellectual disability. PWS involves a complex inheritance pattern and is caused by an absence of gene expression on the paternally inherited 15q11.2-q13 region, either due to deletion, maternal uniparental disomy or imprinting defect. The syndrome is characterized principally by severe neonatal hypotonia, a weak suck in infancy that is later followed by hyperphagia and obesity, developmental delay, intellectual disability and short stature. In the case of the chromosome 15q26-qter deletion syndrome or Drayer's syndrome, very few reports have been published. Its characteristics include intrauterine growth restriction, postnatal growth failure, varying degrees of intellectual disability, developmental delay, typical facial appearance and diaphragmatic hernia. The present paper describes a female patient in whom clinical findings were suggestive of PWS and deletion in the 15q26-qter region. Both karyotyping and methylation-specific polymerase chain reaction were shown to be normal. Nevertheless, fluorescence in situ hybridization showed a 15qter deletion that was later mapped by single nucleotide polymorphism (SNP)-array. The deleted genomic region involves the insulin-like growth factor-1 receptor (IGF1R) gene, which is related to short stature, developmental delay and intellectual disability. This case had various clinical characteristics in common with the cases of 15q26-qter deletionand characteristics compatible with PWS.