Trisomy 6qter

A previously reported patient with trisomy for the distal part of 6q was shown by R-banding to be trisomic for 6q26qter, due to a t(6;22)(q26;p12) mat. Altogether nine patients with 6qter trisomy have been reported. The main features of the 6qter trisomy syndrome are: severe mental and growth retardation; acrocephaly and brachycephaly; a carp-shaped mouth; micrognathia; a very short neck with unusual anterior webbing; joint contractures; the absence of severe inner organ malformations; and survival into adulthood.     

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.     

Reciprocal translocation mosaicism in man

We report on an8-month-old girl with a de novo 5q/6q autosomal translocation with loss of the distal part of the long arm of chromosome 6 (6q23.3→6qter); clinical manifestations are peculiar craniofacial stigmata, truncal obesity and persisting hypotonia. The similarity with a previously reported patient with 6q interstitial deletion is discussed.     

Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother,derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies

We report on a 19-month-old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,?9,?12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low-set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley-Liss, Inc.     

Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion

Wauters JG, Bossuyt PJ, Roelen L, van Roy B, Dumon J. Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion. Clin Genet 1993: 44: 262–269. © Munksgaard, 1993
We report the prenatal diagnosis of a karyotype 46,XY,rec(6)dup p, inv(6) (p23q27) mat detected by fluoroscence in situ hybridization using chromosome 6pter and 6qter specific DNA markers. This partial duplication-deletion (6p12→pter; 6q27→qter) emanated from a balanced pericentric inversion 46,XX inv(6) (p23q27)pat present in the mother. The phenotypes of two relatives with the same unbalanced anomaly are described. This report illustrates the sensitivity and specificity of fluorescence in situ hybridization (FISH) and its benefit in rapid and unequivocal prenatal diagnosis of subtle chromosomal rearrangements.     

易位点在随体的2q37缺失综合征患儿的临床及遗传学分析

目的对1例儿童多动症患儿进行细胞以及分子遗传学检测以明确诊断。方法常规进行外周血细胞培养制片及核型分析,荧光原位杂交(fluorescence in situ hybridization,FISH);常规提取外周血DNA,进行单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP-array)检测。结果患儿具有典型的面部畸形,包括耳位低、耳廓卷曲、眉弓高突、鼻孔凹口、人中短平、上唇薄等。SNP-arry检测显示患儿染色体2q37区存在4.883 Mb的缺失,综合各项检测结果,患儿染色体核型最终被确定为45,XY,der(2;21)(2pter→2q37.3∷21p13→21p10∷20p10→20pter),der(20)(21qter→21q10∷20q10→20qter)。结论报道了1例涉及3条染色体的易位点发生在随体的2q37缺失综合征,综合运用各种细胞及分子遗传学技术对复杂结构染色体异常的诊断十分重要。     

Axenfeld‐Rieger anomaly,hypertelorism, clinodactyly,and cardiac anomalies in sibs with an unbalanced translocation der(6)t(6;8)

We describe two sibs with the unbalanced translocation der(6)t(6;8)(p25.1;q24.23), making them monosomic for 6p25.1→6pter and trisomic for 8q24.23→8qter. The siblings both possess Axenfeld‐Rieger Anomaly (ARA), hypertelorism, clinodactyly, and cardiac anomalies, but otherwise vary in the phenotypic manifestations of this unbalanced translocation. We compare them to previously described cases and a recently proposed syndrome of ARA, atrial septal defect, and sensorineural deafness. © 2001 Wiley‐Liss, Inc.     

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.     

Monosomy 6q: report on four new cases

We report on four patients with partial monosomy of the long arm of chromosome 6: two children presenting with an interstitial deletion del(6)(q14q16), the two others presenting with a terminal deletion del(6)(q25qter). These patients are compared with previous reports in the literature: 16 cases of terminal deletion and 17 cases of interstitial deletion. The deletions most often occur de novo. Mental retardation is always described. Dysmorphic facial features range between minor and major. There may be associated visceral abnormalities. After comparing the size and the localisation of the deletions with clinical data, we are now able to suggest a clinical localisation on chromosome 6.     

Monosomy 9p24→pter and trisomy 5q31→qter: Case report and review of two cases

Partial deletion of the short arm of chromosome 9 (p24→pter) and partial duplication of the long arm of chromosome 5 (q32→qter) were observed in an abnormal boy who died at age 8 weeks of a complex cyanotic cardiac defect. He also had minor anomalies, sagittal craniosynostosis, triphalangeal thumbs, hypospadias, and a bifid scrotum. Two other infants with similar cytogenetic abnormalities were described previously. These patients had severe congenital heart defect, genitourinary anomalies, broad nasal bridge, low hairline, apparently low-set ears, short neck, and triphalangeal thumbs, in common with our patient. We suggest that combined monosomy 9p23,24→pter and trisomy 5q31,32→qter may constitute a clinically recognizable syndrome. © 1995 Wiley-Liss, Inc.     

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.     

Syndromal obesity due to paternal duplication 6(q24.3-q27)

The likelihood of a paternally expressing imprinted gene in chromosome region 6(q23-24) has been highlighted by cases of transient neonatal diabetes mellitus (TNDM) in which paternal uniparental disomy (UPD) for chromosome 6 or paternal duplication 6(q23-qter) was detected. We present the case of a 38-year-old man with moderate to severe intellectual delay, short stature, small hands and feet, eye abnormality, small mouth, and obesity (without hyperphagia) beginning in mid-childhood. The perinatal and neonatal histories were normal. The patient had a duplication within 6q. Fluorescence in situ hybrisation studies were performed with single and dual hybridisations using a chromosome 6 library probe, short and long arm subregional probes, 6q23-24, 6q25.3-6qter locus-specific probes, and a 6q telomere probe. The hybridisation results defined an inverted duplication of 6q24.3 to 6q27. DNA studies with microsatellite markers from 6p and 6q showed regular biparental inheritance of chromosome 6 and confirmed that the duplication was paternal in origin. Our patient appears to be the first one known to have paternal duplication of chromosome area 6(q24-q27) who did not have TNDM as an infant. He has remained nondiabetic, although obesity, without hyperphagia, has been a constant problem since its onset in mid-childhood. Am. J. Med. Genet. 84:125–131, 1999. © 1999 Wiley-Liss, Inc.     

Midtrimester diagnosis and anomalies in the dup(22q) syndrome: Correlation of aneuploidy with low maternal serum alpha-fetoprotein and oligohydramnios

We present the first reported case of prenatally diagnosed dup(22q) syndrome in a 20-year-old woman referred for genetic counseling because of a low maternal serum alphafetoprotein value. An ultrasound study at 22 weeks demonstrated oligohydramnios, intrauterine growth retardation, multiple facial malformations, and a cardiac defect. Fetal karyotype was 46, XYdup(22)(pter→q13:: q12→qter) by amniocentesis. Necropsy following pregnancy termination confirmed all prenatally delineated anomalies. Comparison is made with the complete and partial proximal dup(22q) syndromes. We emphasize the correlation between aneuploidy and the presence of low maternal serum alpha-fetoprotein, oligohydramnios, and midgestational intrauterine growth retardation.     

Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring

We report on a case of constitutional mosaicism for a large pericentric inversion of chromosome 9 in a man whose daughter had recombinant aneusomy resulting in partial 9q duplication and partial 9p deletion. At age 6 months, the girl was evaluated because of dysmorphic congenital animal features and developmental delay. Chromosomal analysis on this infant showed a derivative chromosome 9 which was later determined to be a recombinant chromosome with trisomy of 9q34.1→qter and monosomy of pter→9p24. Chromosomal analysis in her father showed the presence of two cell lines; 75% of lymphocytes had a 46,XY pattern, and 25% had a 46,XY,inv(9)(p24q34.1) karyotype. The infant's physical findings represent a composite of the reported cases of both trisomy 9q34.1→qter and monosomy pter→9p24. The infant's father was phenotypically and cognitively normal. This case broadens the spectrum of reported cases of mosaicism for an autosomal structural rearrangement generating unbalanced gametes, and further supports the tenet that constitutional mosaicism has clinical relevance for genetic counseling. Am. J. Med. Genet. 69:360–364, 1997. © 1997 Wiley-Liss, Inc.     

Natural history of the recombinant (8) syndrome

The recombinant 8 [Rec(8)] syndrome [rec(8), (8qter→8q22.1::8p23.1→8qter] is due to a parental inv(8)(8pter→8p23.1::8q22.1→8p23.1::8q22.1→8qter). All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype consists of a characteristic set of minor facial anomalies, cardiovascular and other major malformations, and moderate to severe mental retardation. The clinical phenotype is relatively consistent in all published cases; however the natural history of the condition has remained unknown. Retrospective and prospective information on 42 propositi, spanning a period from 5 days to 23 years, allowed us to define the natural history of this syndrome, tabulate the frequency and the evolution of phenotypic abnormalities, and share our experience with different therapeutic approaches. © 1993 Wiley-Liss, Inc.     

Molecular characterization of a complex translocation in a newborn infant

A newborn infant was referred because of low-set ears, mild downward slant of the palpebral fissues, micrognathia with higharched palate, a flat midface, small mouth, and thin upper lip with cupid bow configuration. To some extent her cry resembled that associated with cri du chat syndrome. Cytogenetic findings with G- and Q-banding alone failed to characterize precisely the complex translocations. By the chromosome in situ suppression (CISS) hybridization technique using whole chromosome specific probes, a complex 4 breakpoint rearrangement involving both arms of a single chromosome 1 with the long arms of chromosome 5 and 11 was disclosed, i.e., 46,XX, der(1),t(1;5) t(1;11) (5qter→5q31::1p31.3→1q44::11q23→11qter;5pter→5q31::1p31.3→1pter;11pter→11q23::1q44→1qter). Gene deregulation and position effect may explain the multiple anomalies in individuals with apparently balanced translocations may shed some light towards unveiling the clinical consequences associated with aberrations which are presumably balanced. © 1993 Wiley-Liss, Inc.     

Pure familial 6q21q22.1 duplication in two generations

Familial transmissions of unbalanced chromosomal abnormalities are rare. We report here the first case of a maternally inherited pure partial duplication of the long arm of chromosome 6 [46,XX,dup(6)(q21q22.1)mat]. The proband was referred for karyotyping as she presented intrauterine growth retardation (IUGR), moderate mental retardation and facial dysmorphism. Molecular cytogenetics analysis with various BACs showed a duplication of 5-10 Mb between 6q21 and 6q22.1. The proband's mother was found to have the same chromosome abnormality and a similar phenotype, but less severe dysmorphism. This variability in clinical findings between generations may have several causes, including attenuation with aging, imprinting or mosaicism. Only three other cases of pure partial 6q duplication similar to that of our case have been reported. The available information for all four cases was used to refine the karyotype-phenotype correlations for duplications of the 6q21q22 segment.     

Neuroblastoma in a boy with MCA/MR syndrome,deletion 11q,and duplication 12q

Deletion 11q23→qter and duplication 12q23→qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23→24 in the cause of the neuroblastoma is discussed. © 1995 Wiley-Liss, Inc.     

Scattered memorabilia: A living history autobiography of Harold F. Falls

We report on a 4-year-old girl with distinctive facial features (redundant skin, bushy eyebrows, narrow palpebral fissures, short, upturned nose, epicanthal folds, and a long upper lip with well-defined philtrum) who has an interstitial deletion of chromosome 14 including band 14q31, designated as 46,XX,del(14) (pter→q24.3::q32.1→qter). Comparison with previously reported patients with deletions of 14q involving band 14q31 suggests that there is a distinctive clinical phenotype associated with this deletion. Our patient had dental abnormalities (3 maxillary and 3 mandibular incisors) not described in the other patients. © 1992 Wiley-Liss, Inc.     

Unique karyotypes in two patients with Prader-Willi syndrome

A physical disruption of the Prader-Willi syndrome (PWS) chromosome region is thought to cause PWS. We describe 2 girls with PWS phenotype, who had unique chromosome 15 abnormalities. The first patient showed mosaicism: 45,XX,t(15;15)(qter→p11.1::q11.200→ qter)/46,XX,t(15;15)(qter → p11.1::q11.200→ qter), + mar. The band 15q11.2 apparently remained intact in the t(15;15) chromosome, and the mar chromosome was considered as r(15) (p11.1q11.1). The second patient had a karyo-type of 47,XX,del(15)(q11.200→q11.207), + idic (15)(pter → q11.1::q11.1→pter). The complex breakage and reunion involving the 15q11.2 regions of the father's homologous chromosomes 15 at meiosis appeared to have resulted in the idic(15) and the del(15) chromosomes. These cytogenetic findings suggest that the PWS chromosome region may be localized on the very proximal portion of band 15q11.2.