Duplication of part of chromosome 1q: Clinical report and review of literature

We report a male infant with a 47,XY,+der(22),t(1;22)(q32;q11)pat karyotype. Thus, he has duplication of chromosomes 1(q32→qter) and 22(pter→q11). Six patients with dup 1(q32→qter) and eight with dup 1(q42→qter) have been described. These two groups of patients share several manifestations, including postnatal growth retardation; relative macrocephaly with widely separated sutures or large fontanelles; prominent forehead; highly arched palate; micrognathia; downward slant of the palpebral fissures; broad, flat nasal bridge; and apparently low-set, malformed ears. Although many of these abnormalities are nonspecific, partial duplication of 1q should be considered in infants with relative macrocephaly, large fontanelles, and downward slant of the palpebral fissures. Our patient had duplication of the part of chromosome 22 that may be associated with the clinically variable cat-eye syndrome. Patients with dup 22(pter→q11) may also have downward slant of the palpebral fissures, micrognathia, and apparently low-set, malformed ears. The structural gene locus for β-glucosidase has been mapped to chromosome 1. β-Glucosidase activity in fibroblasts from our patient was normal, and his parents' activities were not significantly different from those of control individuals. Therefore, either the locus for this enzyme is not present on 1(q32→qter) or the enzyme does not consistently show a substantial gene-dose effect.     

Origin of a paternal (13q; 15q) translocation leading to dup(13q) in two half sibs

We report on two half-sibs, a male and a female with dup(13)(q1405 → qter) that resulted from a der(15),t(13;15)(15qter → 15q25::13q1405 → 13qter), h +, pat. Their manifestations were similar to those with duplication of the distal half 13q. The father was a balanced de novo translocation carrier. Since the der(15) had a long secondary constriction, it was possible to trace the site of the mutation to the germ cell of the patients paternal grandmother who had this distinctive long secondary constriction in one of her normal 15 chromosomes.     

Precise mapping of a de novo duplication 18(q21→q22) utilizing cytogenetic,biochemical, and molecular techniques

We describe the first de novo inverted duplication of 18q. Due to the difficulty of identifying de novo chromosome abnormalities based solely on cytologic studies, precise definition of the 18q duplication was attempted by integrating cytogenetic and clinical findings with biochemical and molecular dosage studies. The combined results demonstrated that the proposita had a duplication of 18q21→q22 with a karyotype of 46,XX,–18,+inv dup(18) (pter→q12.1::q22→q21::q12.1→qter). The duplication of this specific chromosome region does not result in the typical 18 phenotype, supporting the hypothesis that various loci on chromosome 18 may interact to produce the manifestations of this syndrome. © 1993 Wiley-Liss, Inc.     

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley-Liss, Inc.     

Segregation of a familial balanced (12;10) insertion resulting in dup(10)(q21.2q22.1) and del(10)(q21.2q22.1) in first cousins

An interchromosomal insertion in 3 generations of a family was ascertained through two developmentally delayed first cousins. Cytogenetic analysis using G-banding and chromosome painting showed an apparently balanced direct insertion of chromosome 10 material into chromosome 12, ins(12;10)(q15;q21.2q22.1), in the mothers and grandfather of these children. The proposita inherited only the derivative 10 chromosome, resulting in deletion of 10q21.2 → 22.1 while her cousin inherited only the derivative 12, resulting in duplication of 10q21.2 → 22.1. A comparison of the proposita with published deletion cases suggests a pattern of anomalies attributable to deletion of the 10q21 → q22 region: developmental delay, hypotonia, a heart murmur, telecanthus, broad nasal root and ear abnormalities. This is the first report of a nontandem duplication of the 10q21 → q22 region. The phenotype of the cousin with the duplication does not overlap greatly with published tandem 10q duplications. Finally, this report reaffirms the importance of obtaining family studies of patients with interstitial chromosomal abnormalities. Am J. Med. Genet. 69:188–193, 1997. © 1997 Wiley-Liss, Inc.     

Confirmation of proximal 1q duplication using fluorescence in situ hybridization

We report on a boy with excessively wrinkled skin, mild micro/brachycephaly with mild hydrocephalus and slightly small temporal lobes, apparently low-set ears, retro/micrognathia and cleft soft palate (Pierre-Robin anomaly), patent ductus arteriosus and foramen ovale, pulmonary hypoplasia, eventration of the left hemidiaphragm, right cryptorchidism, a sacral dimple, flexion contractures of fingers and knees, and equinovarus deformities of both feet. The infant had a de novo dir dup(1)(pter→ q25::q12→qter). Partial duplications involving proximal 1q have rarely been reported. Furthermore, this is the first case of proximal duplication of chromosome 1q with unequivocal identification using fluorescence in situ hybridization (FISH) with a chromosome 1 painting probe. © 1994 Wiley-Liss, Inc.     

Malformation syndrome of duplication 12q24.1→qter

While duplication and deletion of the short arm of chromosome 12 cause well-recognized syndromes, duplication of the long arm of chromosome 12 is rarely observed. We are reporting a duplication of chromosome 12 distal to band q24.1 in a five-month-old child. His chromosome constitution is 46,XY,-4, + der(4),t(4:12)(p16;q24.1)mat. The balanced translocation is also carried by his maternal grandmother and two of the mother's brothers. The malformation syndrome consisted of unusual facial appearance and anomalies of the musculoskeletal, cardiovascular, genitourinary, and central nervous systems. Four previously reported patients had similar break points on chromosome 12 with similar malformations; therefore, phenotype-karyotype correlation suggests a definitive malformation syndrome associated with duplication of chromosome region 12q24.1→qter.     

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.     

Small terminal deletion of 1p and duplication of 1q: Cytogenetics,FISH studies,and clinical observations at newborn and at age 16 years

A small, extra chromosome segment added to 1p was found by Q-banding 16 years ago in a newborn baby with low birth weight, short stature, wide open fontanelle, small palpebral fissures, depressed nose bridge, and inguinal hernia. This chromosome abnormality has been characterized recently with G-banding and fluorescence in situ hybridization using multiple DNA probes. The karyotype is now described as 46,XY, der(1)(qter→p36.13::q42.3→qter), representing a small deletion of 1p36.13-pter and a small duplication of 1q42.3-qter. Re-examination of this patient at age 16 years showed marked psychomotor delay, severely accentuated dorsal kyphosis and scoliosis, pectus excavatum, and other anomalies but no clinical signs of neuroblastoma. Comparison of the clinical findings in this case with those described in the patients having either a deletion of 1p36-pter or a duplication of 1q42-qter further illustrated the complexity of the genotype-phenotype relationship. Am. J. Med. Genet. 86:118–123, 1999. © 1999 Wiley-Liss, Inc.     

Characterization of a de novo unbalanced translocation t(14q18q) using microdissection and fluorescence in situ hybridization

We report on a patient with a de novo translocation between the long arms of chromosomes 14 and 18. The translocation was studied using microdissection in combination with fluorescence in situ hybridization (micro-FISH). Five copies of the chromosomes involved in the translocation were isolated by microdissection and amplified by means of degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Reverse chromosome painting with the biotin-labeled PCR product showed that part of the q-arm of chromosome 18 had no signal. The deletion was characterized further by FISH with band-specific probes and it was concluded that the rearrangement was unbalanced: 46,XY,t(14;18)(14pter→4q22::18q21.1→18qter)(18pter→18q12.2::14q22→14qter). The patient, who presented with psychomotor retardation, mild obesity, pes equinovarus, strabismus, and facial anomalies, is compared with previously reported patients with an interstitial deletion of band 18q12. Am. J. Med. Genet. 75:409-413, 1998. © 1998 Wiley-Liss, Inc.     

Meiotic segregation in familial reciprocal translocation t(8q;22q)

We studied the chromosomes of a mentally retarded boy with minor anomalies and of his parents using a G-band stained high-resolution chromosome method. This documented dup (8q24.1 → 8qter) and dup(22pter → 22q11.2) in the boy due to a maternal balanced reciprocal translocation of chromosomes 8 and 22 and 3:1 disjunction during meiosis I. The karyotype of the boy is 47, XY, + der(22) (22pter → 22q11.2::8q24.1 → 8qter). The der(22) was involved in satellite associations and stained positively with AgNO₃ in mother and child. The case is compared to similar cases in the literature and the function of the small acrocentric marker chromosome during meiosis is discussed.     

Cryptic subtelomeric translocations in the 22q13 deletion syndrome

Cryptic subtelomeric rearrangements are suspected to underlie a substantial portion of terminal chromosomal deletions. We have previously described two children, one with an unbalanced subtelomeric rearrangement resulting in deletion of 22q13→qter and duplication of 1qter, and a second with an apparently simple 22q13→qter deletion. We have examined two additional patients with deletions of 22q13→qter. In one of the new patients presented here, clinical findings were suggestive of the 22q13 deletion syndrome and FISH for 22qter was requested. Chromosome studies suggested an abnormality involving the telomere of one 22q (46,XX,?add(22)(q13.3)). FISH using Oncor D22S39 and Vysis ARSA probes confirmed a terminal deletion. A multi-telomere FISH assay showed a signal from 19qter on the deleted chromosome 22. Results were confirmed with 19qtel and 22qtel specific probes. The patient is therefore trisomic for 19qter and monosomic for 22qter. The patient''s mother was found to have a translocation (19;22)(q13.42;q13.31). We also re-examined chromosomes from two patients previously diagnosed with 22q deletions who were not known to have a rearrangement using the multi-telomere assay. One of these patients was found to have a derivative chromosome 22 (der(22)t(6;22)(p25;q13)). No evidence of rearrangement was detected in the other patient. Thus we have found the 22q13 deletion to be associated with a translocation in three of four patients. This report illustrates the usefulness of examining patients with hypotonia, severe language delay, and mild facial dysmorphism for this syndrome and suggests that most of these deletions may be unbalanced subtelomeric rearrangements.     

Trisomy 6q25→6qter in two sisters resulting from maternal 6;11 translocation

Chromosome banding was used to define a partial duplication of the long arm of chromosome 6 (6q25→6qter) in two profoundly affected sisters and to identify their phenotypically normal mother and sister as balanced translocation carriers whose karyotypes were interpreted as 46,XX,t(6;11) (q25;q25). Prominent clinical features included profound mental retardation, hypertelorism, micrognathia, down-turned mouth, dental anomalies, clubfeet, webbed neck, late progressive scoliosis, flexion contractures, and low total finger ridge count. By comparison with published reports, it has been possible to establish a trisomy 6q25→6qter syndrome.     

Duplication of distal 17q: Report of an observation

We describe a boy with the syndrome due to dup(17q) resulting from a paternal balanced t(12;17) (q24;q23). The comparison of the clinical findings in our patient with those previously reported shows that the dup(17q23 → qter) is associated with a clinically recognizable syndrome. Anomalies present in ≥ 75% of the patients were severe psychomotor retardation; short stature; microcephaly; frontal bossing and temporal retraction; widow's peak; narrow palpebral fissures; flat nasal bridge; thin upper lip overlapping thin lower lip; downturned corners of the mouth; apparently low-set, posteriorly angulated and malformed ears; low posterior hairline; widely spaced nipples; cryptorchidism; proximal limb shortness; and hyperlaxity of limb joints. The translocation carrier father of our patient had a Poland anomaly.     

High risk for unbalanced segregation of some reciprocal translocations: A large pedigree containing distal 4q trisomy from t(4;7)(q28;p22)

We report on a familial t(4;7)(q28;p22) with 2:2 adjacent‐1 unbalanced segregation producing duplication of 4q28→qter in multiple offspring. Within the large four‐generation pedigree, a carrier had a reproductive outcome that was approximately equal for 1) the balanced translocation, 2) normal chromosomes, and 3) viable 4q trisomy or pregnancy loss. The three individuals with chromosomal confirmation of trisomy 4q28→qter (comprising approximately 1.8% of the haploid autosomal length) had similar mental and developmental retardation, hypotonia, restricted speech, seizures, and facial anomalies but no cardiac, renal, or skeletal anomalies. It is suggested that these latter severe malformations, associated with the classic 4q2 to 3 group of anomalies, were from an imbalance outside 4q28→qter and were not necessarily related to the relatively large size of the trisomic segment. Multiple different chromosomes are reported to be rearranged with 4q in the production of distal 4q trisomy. The incidence of 4q rearrangement remains unexplained, but once it is present in a family, viability of a large trisomy in 4q seems to explain the number of affected individuals reported. © 2001 Wiley‐Liss, Inc.     

Ebstein anomaly associated with rearrangements of chromosomal region 11q

Ebstein anomaly (EA) is a relatively uncommon congenital heart defect and it is very rarely associated with a chromosomal anomaly. We report two distinct rearrangements of the chromosomal region 11q arm in two unrelated patients with Ebstein anomaly, renal malformation, minor anomalies, and the Pierre Robin sequence. The first patient had an interstitial deletion of chromosome 11 [46,XY,del(11)(11q21q23), and the other had a tertiary trisomy of chromosome 11qter (47,XX,+der(22)t(11;22)(q23; q11.2) Its association with either a chromosome 11q deletion or a duplication in some individuals suggests that a rearrangement of the 11q region is likely to cause a shift of the individuals' underlying liability to develop EA above a certain threshold. Am. J. Med. Gen. 80:157–159, 1998. © 1998 Wiley-Liss, Inc.     

Trisomy 1q42→qter in a sister and brother: Further delineation of the “trisomy 1q42→qter Syndrome”

We report on a 22-year-old woman and her 21-year-old brother with mild mental retardation, long face, prominent forehead, retrognathia, and (relative) macrocephaly. At birth they were small for date, their length is now below the 10th centile. Chromosome analysis demonstrated a nearly pure trisomy 1q42→qter in both patients due to unbalanced segregation of a paternal reciprocal balanced translocation 46,XY,t(1;15) (q42;p11). This is the second report of a nearly pure trisomy 1q42→qter. When comparing the manifestations of our patients with those of other reported cases we conclude that the most characteristic clinical manifestations of this syndrome are macrocephaly, prominent forehead, micro/retrognathia, large fontanelle, intrauterine growth retardation, postnatal growth retardation, and mental retardation. © 1995 Wiley-Liss, Inc.     

Inverted tandem (“mirror”) duplications in human chromosomes: Inv dup 8p, 4q, 22q

We have studied 4 patients with inverted tandem duplications of parts of chromosomes, a hitherto rarely identified from of a structural rearrangement involving a single chromosome in man. In Patients 1 and 2, the duplication involved parts of the short arm of chromosome 8 (regions 8p 12→8p23 and 8p21→8p23, respectively). Both patients manifested certain characteristics of the mosaic trisomy 8 syndrome. Elevated levels of glutathione reductase (GSR) in their erythrocytes supported the interpretation of a partial duplication of chromosome 8 and indicated a regional localization for the GSR gene locus. In Patient 3, the distal half of the long arm of chromosome 4 was duplicated (region4q26→4q35). Clinical evidence supported this interpretation, as Patient 3 resembled phenotypically the 13 reported cases with duplication of the distal 4q. The cytogenetic findings in Patient 4 suggested a possibly inverted duplication of 22q. The clinical correlation was less convincing due to the lack of a well-defined phenotype for trisomy 22. These chromosome aberrations had occurred de novo in all 4 cases. Although they involved different chromosomal regions, they might well have arisen by the same mechanism. Possible modes of origin that are discussed in detail include unequal exchange between homologous chromosomes, between chromatids of 1 chromosome or between strands of 1 DNA duplex.     

Case report of rec(7)dup(7q)inv(7)(p22q22) and a review of the recombinants resulting from parental pericentric inversions on any chromosomes

We report a rare case of duplication for 7q22 → 7qter and deletion for 7p22 → 7pter, resulting from a meiotic recombination of a paternal pericentric inversion, inv(7)(p22q22). The newborn boy had the 7q trisomy syndrome. In addition, the diagnosis of chondrodysplasia punctata was made from lumbar and hand X-ray films taken soon after birth. Only two cases of rec(7)dup(7q), both in a single family, have been reported previously. We review 133 offspring with recombinations resulting from pericentric inversions on any chromosomes reported between 1981 and 1995. Of the 133 cases, 110 had a long-arm duplication and short-arm deletion, while only 23 had a short-arm duplication and long-arm deletion. In 85 of the 133 cases, the mother was an inversion carrier (five carriers had two affected offspring), and in 46, the carrier was a father (one carrier had three affected offspring). Kaiser [Hum Genet 1984;68:1–47] reviewed 63 offspring with recombinations derived from a parental pericentric inversion reported between 1972 and 1981. In both surveys, recombinations resulting from pericentric inversions of chromosomes 1, 12, 19, and Y were not found. Am. J. Med. Genet. 73:290–295, 1997. © 1997 Wiley-Liss, Inc.     

Ring-11 chromosome: Phenotype-karyotype correlation with deletions of 11q

The cytogenetic evaluation of a female infant with congenital anomalies led to the identification of the second reported case of a ring-11 chromosome. Unlike the previously described case, in which the patient had only minimal clinical findings and no demonstrable loss of material from the ring, our patient had numerous anomalies that were asssociated with a substantial deficiency of 11q material. The different phenotypes in these two cases represent variation in the amount and location of the chromosomal material lost during the genesis of the ring. The manifestations of this patient and the deletion of region q24→qter from the ring-11 identify a specific chromosome deletion syndrome referred to as del (11q) syndrome.