Distal Trisomy Research Articles

EP112: Septo-optic dysplasia associated with unbalanced chromosome translocation resulting in trisomy 11q13 and monosomy 12q24.3

Distal trisomy 11q syndrome is rare and most often associated with a translocation involving chromosome 22 (Emanuel syndrome). Patients with isolated distal trisomy 11q present with intellectual disability, short stature and microcephaly. Birth defects commonly reported with the syndrome include brain malformations, cardiac defects, diaphragmatic hernia, hip dysplasia, and micrognathia or Pierre-Robin sequence. Distal 12q deletion syndrome is even more rare, and associated with developmental delay and intellectual disability.

Prenatal diagnosis of Cri-du-Chat syndrome with concomitant distal trisomy 10q syndrome in one fetus with ultrasound anomalies

ObjectiveThe aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening. Materials and methodsA 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18+4 weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis. ResultsCNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent. ConclusionThis is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.

Prenatal diagnosis of a pure 15q distal trisomy derived from a maternal pericentric inversion: A case report

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

10q distal trisomy and 15q monosomy as a rare genetic cause for intellectual disability

10q distal trisomy and 15q monosomy as a rare genetic cause for intellectual disability

Familial translocation t(5;11)(q32;q23) resulting in Jacobsen syndrome and distal trisomy 5q31 in a female patient

Familial translocation t(5;11)(q32;q23) resulting in Jacobsen syndrome and distal trisomy 5q31 in a female patient

EP05.06: Distal Trisomy 10q: a rare genetic abnormality with unusual presentation as fetal axillary lymphangioma

EP05.06: Distal Trisomy 10q: a rare genetic abnormality with unusual presentation as fetal axillary lymphangioma

Distal trisomy 3q and distal monosomy 11q in a mother and child with neurodevelopmental delay, short stature, facial dysmorphism and digital malformations

Distal trisomy 3q and distal monosomy 11q in a mother and child with neurodevelopmental delay, short stature, facial dysmorphism and digital malformations

Inherited Unbalanced Chromosome from Parent with Balanced Translocation: A Case Report and Review of Literature

Reciprocal translocations are common, and the translocation heterozygote (carrier) may have a risk to have a child who would be mentally and physically abnormal due to a segmental aneusomy. The carriers of balanced translocation mostly do not have recognizable phenotypic expression, however, they can produce unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. We describe a 4-year-old boy with partial 10q trisomy and distal 13qmonosomy. The patient presented with delayed milestones, dysmorphic face, congenital heart defect, renal and skeletal anomalies. The conventional cytogenetic analysis showed a 46,XY, add(13q) karyotype. The child inherited the unbalanced chromosome from mother who was a carrier of balanced reciprocal translocation,t(10;13)(p24.2;q33.1). The phenotype observed in our patient resulted from the combination of those defects described in the isolated dup(10q) and distal del(13q) syndromes but predominantly resembles the children with distal trisomy 10q syndrome. Our finding are in concordance with the literature and supports the importance of critical regions like 10q24 and 13q32 for the phenotypic expression of distal 10q trisomy syndrome and distal 13q trisomy syndrome respectively.

Distal Trisomy 10p and 4q Monosomy: Associated with Marfanoid Features, Syndromic Aortic Root Dilatation and Intellectual Disability

Distal Trisomy 10p and 4q Monosomy: Associated with Marfanoid Features, Syndromic Aortic Root Dilatation and Intellectual Disability

MG-121 Five new patients with pure distal 1q trisomy, review of the literature and phenotype redefinition

Background Pure distal 1q trisomy is rare and there is limited information on genotype-phenotype correlation. The common 1q trisomy phenotype attributed to the 1q42qter segment is based on a small number of patients and consists of small for gestational age, developmental delay, macrocephaly, dysmorphic features and heart defects. Objective To clarify the genotype-phenotype correlation of pure distal 1q trisomy. Design/method We report five patients with pure distal 1q trisomy: 1q32.2qter (patient 1), 1q41q44 (patient 2), 1q43qter (patient 5) and 1q42.13qter in two siblings (patient 3 and 4). A PubMed search was done to identify patients with trisomies distal to 1q32. Patients with pure 1q trisomies that matched the duplications found in our patients were selected. Results Thirty-three patients have been reported with partial trisomy distal to 1q32. Only 17 patients with pure 1q trisomy matched our patients’: ten for 1q32qter, four for 1q41q44, two for 1q42qter and one for 1q43qter. Our patients presented additional features than the common 1q trisomy phenotype. Patients 1, 2, 3 and 4 have had frequent infections with normal immunological status. Patients 1, 3 and 4 had significant sleeping problems. Patients 3 and 4 have camptodactyly and patient 4 had hypertrophied cardiomyopathy. Patients 4 and 3 respectively have moderate and mild intellectual deficiency, a feature that was thought to be mostly normal distal to the 1q42 region. Conclusions The partial 1q trisomy phenotype is constantly expanding. An improved definition allows for the identification of critical regions and better genetic counselling and follow up.

Distal trisomy 10q syndrome, report of a patient with duplicated q24.31 – qter, autism spectrum disorder and unusual features

Key Clinical MessageWe report on a patient with distal trisomy 10q syndrome presenting with a few previously undescribed physical features, as well as, autism spectrum disorder (ASD). We recommend that patients with distal trisomy 10q syndrome should have a behavioral evaluation for ASD for the early institution of therapy.

Bilateral radial agenesis with absent thumbs, complex heart defect, short stature, and facial dysmorphism in a patient with pure distal microduplication of 5q35.2-5q35.3

BackgroundA partial duplication of the distal long arm of chromosome 5 (5q35-- > qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set dysplastic ears, hypertelorism, almond-shaped, down-slanted palpebral fissures, epicanthal folds, small nose, long philtrum, small mouth, and thin upper lip. Less frequent remarkable findings include craniosynostosis, heart defect, hypoplastic phalanges, preaxial polydactyly, hypospadias, cryptorchidism, and inguinal hernia. In most patients with a partial duplication of 5q the aberration occurred due to an inherited unbalanced translocation, therefore the phenotype was not reflective of pure trisomy 5q.Case presentationWe report on a 9.5-year-old boy with some feature of Hunter-McAlpine syndrome including short stature, complex heart defect (dextrocardia, dextroversion, PFO), bilateral cryptorchidism, hypothyroidism, and craniofacial dysmorphism. Additionally, bilateral radial agenesis with complete absence of Ist digital rays, ulnar hypoplasia with bowing, choroidal and retinal coloboma, abnormal biliary vesicle were identified, which have never been noted in 5q trisomy patients. Karyotype analysis, sequencing and MLPA for TBX5 and SALL4 genes were unremarkable. Array comparative genomic hybridization detected a duplication on 5q35.2-5q35.3, resulting from a de novo chromosomal rearrangement. Our proband carried the smallest of all previously reported pure distal 5q trisomies encompassing terminal 5.4-5.6 Mb and presented with the most severe limb malformation attributed to the increased number of distal 5q copies.ConclusionsWe postulate that a terminal distal trisomy of 5q35.2-5q35.3, which maps 1.1 Mb telomeric to the MSX2 gene is causative for both radial agenesis and complex heart defect in our proband. A potential candidate gene causative for limb malformation in our proband could be FGFR4, which maps relatively in the closest position to the chromosomal breakage site (about 1.3 Mb) from all known 5q duplications. Since the limb malformation as well as the underlying genetic defect are distinct from other 5q trisomy patient we propose that a position effect resulting in altered long-range regulation of the FGFR4 (alternatively MSX2) may be responsible for the limb malformation in our proband.

Distal trisomy 10q24 due to maternal 10;22 translocation, third case in the same family

Abstract Distal trisomy 10q is a well delineated but a rare syndrome with characteristic phenotypic features. We present clinical and cytogenetic data on a 7 day-old girl with distal 10q trisomy (10q24→qter), due to maternal t(10;22) reciprocal translocation. Her karyotype showed an unbalanced translocation between chromosomes 10 and 22, resulting in trisomy of the distal part of the long arm of chromosome 10q24.

1q遠位部トリソミー, 2q遠位部トリソミー, 18q+高精度分染法により診断が改められた症例

1q遠位部トリソミー, 2q遠位部トリソミー, 18q+高精度分染法により診断が改められた症例

Distal trisomy 10q syndrome: phenotypic features in a child with inverted duplicated 10q25.1–q26.3

Distal trisomy 10q syndrome: phenotypic features in a child with inverted duplicated 10q25.1–q26.3

Pure distal trisomy 2q: A rare chromosomal abnormality with recognizable phenotype

We present clinical and molecular cytogenetic results of two unrelated patients with isolated distal trisomy of 2q33-qter and 2q35-q37.3 and a remarkable similar facial appearance. Common craniofacial features included a high hairline, broad nasal bridge, prominent nasal tip, thin upper lip vermillion, and large ears. Contrary to patients with duplications proximal to 2q33, the children with pure trisomy distal to 2q35 have normal or increased body measurements and show no major malformations. Moderate psychomotor delay was a constant finding.

Distal Trisomy of 10q with Distal Monosomy of 15q Due to a Paternal Translocation

Distal trisomy of 10q is a rare chromosomal abnormality. Distal deletions of the terminal long arm of chromosome 15 have rarely been described. We report on a male infant with low birth weight and microcephaly, a flat face with a spacious forehead, low-set ears, blepharophimosis, microphthalmia, a small nose, and a depressed nasal bridge. Microarray comparative genomic hybridization identified that he had the karyotype 46, XY, der (15) t (10;15) (q25.2;q26.2) pat, with chromosomal breakpoints at 10q25.2 and 15q26.2. This male neonatal case had an unbalanced translocation inherited from his father who was a balanced carrier with the karyotype 46, XY, t (10;15) (q25;q26). The neonate had a partial trisomy of the long arm of chromosome 10 with a partial monosomy of distal 15q. The clinical features were in agreement with previous descriptions and allowed us to propose a growth retardation phenotype for this neonate case.

Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype—phenotype maps

We report on 3 kindred patients with terminal 11q monosomy and distal 22q trisomy involving the SHANK3 gene, resulting from a subtle familial translocation t(11;22)(q24.2;q13.33). The patients presented with the characteristic symptoms of Jacobsen syndrome (JBS), including: mental retardation, short stature, and craniofacial dysmorphism in all 3 cases; cardiac defects in 2 cases; and thrombocytopenia, brain abnormality, eye coloboma, recurrent infections, cryptorchidism and toe anomalies in single cases. The oldest patient also had Hashimoto disease and diabetes mellitus type 2. So far, these 2 conditions have not been reported in adult patients with JBS. Features typical for distal 22q trisomy in our patients include muscular hypotonia and prenatal failure to thrive, seen in 2 and 1 cases, respectively. We also present a family member with 11q24.2-qter trisomy and 22q13.33-qter monosomy, whose clinical phenotype is partially overlapping with several dysmorphic features of JBS. In addition, multiple pregnancy losses and infantile deaths occurred in this family, suggesting that these chromosomal imbalances may produce a lethal phenotype. FISH with a panel of BAC probes determined the accurate sizes of the deletion 11q (9.9 Mb) and trisomy 22q (0.8 Mb). To date, only 5 cases of submicroscopic 22q13.3-qter trisomy have been reported. A detailed clinical description of our patients, along with a precise cytogenetic designation of chromosomal breakpoints, allow further refinement of genotype-phenotype correlation for distal imbalances in 11q and 22q.

Sonic Hedgehog deletion and distal trisomy 3p in a patient with microphthalmia and microcephaly, lacking cerebral anomalies typical of holoprosencephaly

About 20% of cases with 7q deletion syndrome is associated with holoprosencephaly (HPE), due to deletion of the Sonic Hedgehog ( SHH) gene (mapping to 7q36). The occurrence of severe forms of holoprosencephaly is higher in cases of 7q deletion associated with partial trisomies involving different parts of the genomes than in patients with pure 7q deletion. All cases of 7q deletion associated with 3p duplication reported to date have been associated with severe forms of holoprosencephaly, and a gene(s) on distal 3p has (have) been hypothesized to be responsible for HPE phenotype when in triple dose. Here we describe a patient with unbalanced 3p;7q translocation, showing 7q deletion (including SHH gene) and 3p duplication (complete karyotype was 46,XY,der(7)t(3;7)(p26.3;q36.1)), presenting with a relatively mild phenotype, consisting of microphthalmia and microcephaly, without cerebral anomalies typical of holoprosencephaly. Possible involvement of some genes on 3p in determining such a mild phenotype is discussed.

Partial monosomy Xq(Xq23 → qter) and trisomy 4p(4p15.33 → pter) in a woman with intractable focal epilepsy, borderline intellectual functioning, and dysmorphic features

Studies of epilepsy associated with chromosomal abnormalities may provide information about clinical and EEG phenotypes and possibly to identify new epilepsy genes. We describe a female patient with intractable focal epilepsy, borderline intellectual functioning, and facial dysmorphisms, in whom genetic study (i.e., karyotype and array-CGH analysis) revealed a distal trisomy 4p and distal monosomy Xq. Although any genetic hypothesis remains speculative, several genes are located in the 4p chromosome segment involved in the rearrangement, some of which may be related to epilepsy.