Trisomy 9p Research Articles

Cytogenetic and clinical description of maternally inherited pure trisomy 4p

Cytogenetic and clinical description of maternally inherited pure trisomy 4p

Epilepsy, EEG and chromosomal rearrangements.

Chromosomal abnormalities are associated with a broad spectrum of clinical manifestations, one of the more commonly observed of which is epilepsy. The frequency, severity, and type of epileptic seizures vary according to the macro- and microrearrangements present. Even within a single chromosomal anomaly, we most often deal with a phenotypic spectrum. The aim of the study was to look for chromosomal rearrangements with a characteristic electroencephalographic pattern. Only a few disorders have peculiar electroclinical abnormalities: 1p36, 4p16, 6q terminal or trisomy 12p, Angelman syndrome, inv dup 15, 15q13.3 deletions, ring 20, Down syndrome, or Xp11.22-11.23 duplication. We also reviewed studies on epileptic seizures and typical electroencephalographic patterns described in certain chromosomal rearrangements, focusing on the quest for potential electroclinical biomarkers. The comprehensive review concludes with clinical presentations of the most common micro and macro chromosomal rearrangements, such as 17q21.31 microdeletion, 6q terminal deletion, 15q inv dup syndrome, 2q24.4 deletion, Xp11.22-11.23 duplication, 15q13.3 microdeletion, 1p36 terminal deletion, 5q14.3 microdeletion, and Xq28 duplication. The papers reviewed did not identify any specific interictal electroencephalographic patterns that were unique and significant biomarkers for a given chromosomal microrearrangement. The types of seizures described varied, with both generalized and focal seizures of various morphologies being reported. Patients with chromosomal anomalies may also meet the criteria for specific epileptic syndromes such as Infantile Epilepsy Spasms Syndrome (IESS, West syndrome): 16p13.11, 15q13.3 and 17q21.31 microdeletions, 5q inv dup. syndrome; Dravet syndrome (2q24.4 deletion), Lennox-Gastaut syndrome (15q11 duplication. 1q13.3, 5q inv dup.); or Self-Limited Epilepsy with Autonomic Features (SeLEAS, Panayiotopoulos syndrome: terminal deletion of 6q.n), Self-Limited Epilepsy with Centrotemporal Spikes (SeLECT): fragile X syndrome. It is essential to better characterize groups of patients to more accurately define patterns of epilepsy and EEG abnormalities. This could lead to new treatment strategies. Future research is required to better understand epileptic syndromes and chromosomal rearrangements. PLAIN LANGUAGE SUMMARY: This paper presents EEG recording abnormalities in patients with various gene abnormalities that can cause epilepsy. The authors summarize these EEG variations based on a literature review to see if they occur frequently enough in other chromosomal abnormalities (in addition to those already known) to be a clue for further diagnosis.

Short report: Twins with 20p13 duplication. Case report and comprehensive literature review.

Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20. We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000. Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell etal. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function. We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.

Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

5p15 Duplication: Clinical Features in a Preterm Infant

Trisomy 5p is a rare chromosomal abnormality that results from the partial or complete duplication of chromosome 5. Commonly reported clinical features of Trisomy 5p include congenital heart defects, respiratory failure, seizures, and developmental delay. To date, all reported cases of Trisomy 5p have been school-aged children or adults. We present the first case of an infant who was born preterm with multiple congenital anomalies and subsequently diagnosed with 5p15.1p11 duplication via whole exome sequencing. While our patient shares some of the major features of classic Trisomy 5p, the infant has other clinical features not previously described.

Large Chromosome 2p Duplication-Associated Mechanisms and Clinical Presentations

Chromosome 2p (chr2p) duplication, also known as trisomy 2p, is a rare chromosome abnormality associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants (CNVs) in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chr2p as the sole cytogenetic abnormality. In this study, 193 samples at the Greenwood Genetic Center (GGC) with CNVs involving chr2p were evaluated, out of which 86 had chr2p duplications. Among them, 8 patients were identified with large chr2p duplications ranging in size from 9.3 Mb to 89 Mb, and no deletions or duplications involving other chromosomes were identified in those patients. These duplications were associated with inverted duplication, tandem duplication, and duplication as the result of translocation, with no additional CNVs identified by microarray analysis. Confirmation by conventional cytogenetics was performed in 7 of the 8 patients, and the translocations were confirmed by fluorescence in situ hybridization. Interestingly, 1 patient was found to have mosaic complete trisomy 2p as the result of an unbalanced de novo (X;2) chromosomal translocation. X-inactivation was skewed toward the derivative X chromosome, yet it did not appear to extend into the chromosome 2 material. Various shared clinical manifestations were observed in the individuals in this study, including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, and they also have distinct features such as hypotonia, cerebellar hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. In conclusion, single-event large chr2p duplications can result from different mechanisms, including inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p is commonly associated with developmental delay, and additional clinical features may be related to gene dosage effects.

Application of various genetic analysis techniques for detecting two rare cases of 9p duplication mosaicism during prenatal diagnosis.

The identification of genetic mosaicism and the genetic counseling needed following its discovery have been challenging problems in the field of prenatal diagnosis. Herein, we describe the clinical phenotypes and various prenatal diagnostic processes used for two rare cases of 9p duplication mosaicism and review the prior literature in the field to evaluate the merits of different methods for diagnosing mosaic 9p duplication. We recorded ultrasound examinations, reported the screening and diagnosis pathways, and analyzed the mosaic levels of the two cases of 9p duplication using karyotype analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization analysis (FISH). Case 1 had a normal clinical phenotype for tetrasomy 9p mosaicism, and Case 2 showed multiple malformations caused by both trisomy 9 and trisomy 9p mosaicism. Both cases were initially suspected after non-invasive prenatal screening (NIPT) based on cell-free DNA. The mosaic ratio of 9p duplication found via karyotyping was lower than what was discovered by CMA and FISH, in both cases. Contrary to previous findings, the mosaic level of trisomy 9 found by karyotype analysis was greater than what was found by CMA, in terms of complex mosaicism involving trisomy 9 and trisomy 9p, in Case 2. NIPT can indicate 9p duplication mosaicism during prenatal screening. Different strengths and limitations existed in terms of diagnosing mosaic 9p duplication by karyotype analysis, CMA, and FISH. The combined use of various methods may be capable of more accurately determining break-points and mosaic levels of 9p duplication during prenatal diagnosis.

Partial trisomy 9p and partial monosomy 7p of an infant inherited from maternal balanced translocation: a case report

BackgroundSubchromosomal deletions and duplications are the leading cause of congenital malformations and mental retardation in children. With the recent clinical application of genomic microarrays in the evaluation of patients with developmental delays and congenital malformations, it has led to the discovery of several new microdeletion and microduplication syndromes. However, there are no published reports involving patients with both microduplications in the 9p21.1-p24.3 region and microdeletions in the 7p22.1-p22.3 region.Case presentationWe report an infant with an autosomal abnormality confirmed by conventional karyotype combined with copy number variations sequencing (CNV-seq), showing the patient with an unbalanced translocation. The karyotype of the patient was 46, XX, der (7)t (7;9) (p22; p21) and CNV-seq results showed an approximately 32.34-Mb duplication in 9p21.1-p24.3 (200000-32540000) and an approximately 3.3-Mb deletion in 7p22.2-p22.3 (40000-3340000).ConclusionsThe patient carried an unbalanced translocation 46, XX, der (7)t (7;9) (p22; p21) derived from her mother. The clinical presentation is closely related to the size and position of the missing and duplicated chromosomes. To our knowledge, the simultaneous occurrence of de novo partial trisomy 9p(9p21.1-p24.3) and partial monosomy 7p (7p22.2-p22.3) has not previously been reported up until now. The present study additionally demonstrated that CNV-seq combined with karyotype is able to reliably detect unbalanced submicroscopic chromosomal aberrations.

Outcomes of two different unbalanced segregations from a maternal t(4;10)(q33;p15.1) translocation

BackgroundUnbalanced translocations can cause developmental delay (DD), intellectual disability (ID), growth problems, dysmorphic features, and congenital anomalies. They may arise de novo or may be inherited from a parent carrying a balanced rearrangement. It is estimated that 1/500 people is a balanced translocation carrier. The outcomes of different chromosomal rearrangements have the potential to reveal the functional consequences of partial trisomy or partial monosomy and can help guide genetic counseling for balanced carriers, and other young patients diagnosed with similar imbalances.MethodsWe performed clinical phenotyping and cytogenetic analyses of two siblings with a history of developmental delay (DD), intellectual disability (ID) and dysmorphic features.ResultsThe proband, a 38-year-old female, has a history of short stature, dysmorphic features and aortic coarctation. She underwent chromosomal microarray analysis, which identified partial monosomy of 4q and partial trisomy of 10p. Her brother, a 37-year-old male, has a history of more severe DD, behavioral problems, dysmorphic features, and congenital anomalies. Subsequently, karyotype confirmed two different unbalanced translocations in the siblings: 46,XX,der(4)t(4;10)(q33;p15.1) and 46,XY,der(10)t(4;10)(q33;p15.1), respectively. These chromosomal rearrangements represent two possible outcomes from a parent who is a carrier for a balanced translocation 46,XX,t(4;10)(q33;p15.1).ConclusionTo our knowledge, this 4q and 10p translocation has not been described in literature. In this report we compare clinical features due to the composite effects of partial monosomy 4q with partial trisomy 10p and partial trisomy 4q with partial monosomy 10p. These findings speak to the relevance of old and new genomic testing, the viability of these segregation outcomes, and need for genetic counseling.

Cases of tetrasomy 9p and trisomy 9p in prenatal diagnosis-Analysis of noninvasive and invasive test results.

Objective: Tetrasomy 9p and trisomy 9p are rare chromosomal aberrations. The phenotypes of tetrasomy 9p and trisomy 9p are variable. Most cases are diagnosed in the postnatal period. The study aims to analyze the prenatal phenotype of tetrasomy 9p and trisomy 9p in terms of ultrasound and screening tests. Methods: A set of 1573 prenatal tests performed from 2016 to 2021 was reviewed to identify all cases with trisomy 9p and tetrasomy 9p. In four cases with 9p gain, non-invasive and invasive test results were analyzed. Results: Four cases with the 9p gain were diagnosed in the prenatal period: two cases with tetrasomy 9p and two cases with trisomy 9p. Nasal bone hypoplasia and ventriculomegaly are common features of 9p gain. In two out of four cases with the 9p gain, an increased risk of trisomy 21 was found in the combined first-trimester screening test. Conclusion: Trisomy 9p and tetrasomy 9p are characterized by a variable phenotype in the prenatal period, manifesting in genetically abnormal fetuses. The tetrasomy 9p and trisomy 9p may suggest trisomy 21 in the first trimester.

Rare combination in an infant patient: trisomy 7p and tetralogy of fallot.

This case report presents an infant patient with the association of trisomy 7p and tetralogy of fallot (TEF). Patients diagnosed with trisomy 7p should certainly be scheduled for an echocardiographic exam and be scanned for any CHDs that may accompany it. The CHDs that most frequently accompany this syndrome include atrial septal defect, ventricular septal defect, and patent ductus arteriosis. Yet, it should be known that TEF may also be present, albeit rarely.

Iris and Ciliary Body Melanocytomas Are Defined by Solitary GNAQ Mutation Without Additional Oncogenic Alterations

To analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication. Retrospective case-control study. Patients with melanocytoma (n= 16) and melanoma (n= 19) of the anterior uvea. Targeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features. Presence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence. Hotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n= 3), EIF1AX (n= 4), SRSF2 (n= 1), PTEN (n=1), and EP300 (n= 1); monosomy 3p (n= 6); trisomy 6p (n= 3); trisomy 8q (n= 2); and an ultraviolet mutational signature (n= 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n= 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized. In this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aidrisk stratification and clinical management decisions.

Prenatal genetic diagnosis of tetrasomy 18p from maternal trisomy 18p: a case report

BackgroundTetrasomy 18p syndrome is a rare chromosomal disorder that is caused by the presence of isochromosome 18p. Most tetrasomy 18p cases are de novo cases and maternal origin of trisomy 18p is a rare condition. At present, only four cases of maternal origin have been reported in worldwide.This is the fifth case of tetrasomy 18p originating from maternal trisomy 18p. The mother of the fetus studied had no apparent disease phenotype.Case presentationThe current case report is to describe a fetus with confirmed 18p tetrasomy as detected by karyotyping and Single Nucleotide Polymorphism array (SNP array) analysis. However, the fetus showed normal phenotypic features that were observed using ultrasound scans. The mother and maternal grandfather were phenotypically normal and healthy; however, they were diagnosed with trisomy 18p, which was confirmed by conventional karyotyping and SNP array.ConclusionsWe report a case of 18p tetrasomy in a fetus whose mother and grandfather had 18p trisomy. The mother and grandfather were phenotypically normal. Our case report findings provide an important reference for the genetic counseling of trisomy 18p in the future.

Molecular cytogenetic characterization of a de novo derivative chromosome X with an unbalanced t(X;9) translocation in a fetus and literature review

Partial trisomy 9p is one of the most frequent autosome anomalies in newborn infants featured by craniofacial dysmorphism, intellectual disability and psychomotor growth. Female patients carrying monosomy Xq usually show mild symptoms due to skewed X-chromosome inactivation (XCI). Unbalanced translocation between chromosome X and chromosome 9 is rare in prenatal diagnosis. The skewed inactivation of abnormal X would spread into the extra segment of chromosome 9 presented in the der(X) leading to mild phenotypes. We reported on a fetus with high risk of trisomy 9p(13.32 Mb 9p23-p24.3 duplication)suggested by noninvasive prenatal testing (NIPT), the fetus was normal by ultrasonography. G-banding with trypsin-giemsa (GTG), copy number variations sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were carried out to delineate the nature of rearrangement. Final karyotype of the fetus was identified as 46,X,der(X)t(X;9)(q27;p23)dn. An unbalanced X-autosome translocation with a deletion of Xqter-q27.2 and a duplication of 9pter-p23 led to mild phenotypes with no obvious alteration by prenatal ultrasonography, or obvious pathological alterations after pregnancy termination.

17. Chromosome 2p duplication associated mechanisms and clinical presentations

Chromosome 2p duplication, also known as trisomy 2p, is a rare chromosome abnormality, which is associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chromosome 2p alone. In this study, we analyzed 8 patients with large chromosome 2p duplications ranging in size from 9.3 Mb to 89 Mb. These duplications were identified in association with inverted duplication, tandem duplication, and duplication as the result of translocation, with no other copy number variant identified by microarray analysis. Seven out of 8 patients had confirmation by conventional cytogenetics and all of the translocations were confirmed by FISH. Interestingly, one case is a patient with mosaic complete trisomy 2p, who has a de novo (X;2) chromosomal translocation. X-inactivation was shown for the derivative X chromosome, yet it does not appear to extend into the chromosome 2 material. While patients share common clinical manifestations including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, they also have distinct features such as hypotonia, cerebellar agenesis/hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. Triplosensitivity has been reported in patients with duplications covering 2p24.3 region. Global developmental delay and autism have also been reported in patients with de novo microduplications of 2p15p16.1. In conclusion, large chromosome 2p duplications could result from inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p are commonly associated with developmental delay, and additional clinical features may be related to gene dosage effect.

18. Trisomy 18p detected in DNA from saliva but absent in DNA from blood

Molecular diagnostic testing using DNA from saliva specimens markedly increased recently due to the ease of sample collection, compared to peripheral blood, during the COVID-19 pandemic. Published literature suggests that DNA from saliva is primarily composed of epithelial cells (70-90%), with the remainder being primarily leukocytes (10-30%). Here, we describe a case followed by our clinicians since 2007 characterized by developmental delay, autism, a somewhat coarse face with full cheeks, up-slanting palpebral fissures, thin corpus callosum, and a full-scale IQ of 60.

Congenital hydrocephalus in a trisomy 9p gained child: a case report

BackgroundHydrocephalus caused by excessive liquor production due to choroid plexus hyperplasia is a rare condition that may necessitate unusual treatment paradigms. It can be seen in trisomy 9p where coexisting congenital heart disease additionally may complicate the therapeutic approach as illustrated in the current case report.Case presentationAt 20 months of age, a Caucasian girl with trisomy 9 and family history of an older brother and twin sister having the same syndrome displayed sign of congenital hydrocephalus due to increasing head circumference. Magnetic resonance imaging revealed enlarged lateral ventricles and a prominent choroid plexus, and the girl was treated with a ventriculoperitoneal shunt, which 2 days later had to be replaced with a ventriculoatrial shunt as cerebrospinal fluid formation greatly exceeded the ability of the patient’s abdominal absorptive capability. At 16 years of age, the patient was diagnosed with cardiomyopathy and diminished ejection fraction. Some months later, she was admitted to the neurosurgical ward showing signs of shunt dysfunction due to a colloid cyst in the third ventricle. Cystic drainage through endoscopic puncture only helped temporarily. Revision of the shunt system showed occlusion of the ventricular drain, and replacement was merely temporary alleviating. Intracerebral pressure was significantly increased at around 30 mmHg, prompting externalization of the drain, and measurements revealed high cerebrospinal fluid production of 60–100 ml liquor per hour. Thus, endoscopic choroid plexus coagulation was performed bilaterally leading to an immediate decrease of daily cerebrospinal fluid formation to 20–30 ml liquor per hour, and these values where stabilized by pharmaceutical treatment with acetazolamide 100 mg/kg/day and furosemide 1 mg/kg/day. Subsequently a ventriculoperitoneal shunt was placed. Follow-up after 1 and 2 months displayed no signs of hydrocephalus or ascites.ConclusionsHigh cerebrospinal fluid volume load and coexisting heart disease in children with trisomy 9p may call for endoscopic choroid plexus coagulation and pharmacological therapy to diminish the daily cerebrospinal fluid production to volumes that allow proper ventriculoperitoneal shunting.

Characterization of a rare mosaic unbalanced translocation of t(3;12) in a patient with neurodevelopmental disorders

BackgroundUnbalanced translocations may be de novo or inherited from one parent carrying the balanced form and are usually present in all cells. Mosaic unbalanced translocations are extremely rare with a highly variable phenotype depending on the tissue distribution and level of mosaicism. Mosaicism for structural chromosomal abnormalities is clinically challenging for diagnosis and counseling due to the limitation of technical platforms and complex mechanisms, respectively. Here we report a case with a tremendously rare maternally-derived mosaic unbalanced translocation of t(3;12), and we illustrate the unreported complicated mechanism using single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and chromosome analyses.Case presentationAn 18-year-old female with a history of microcephaly, pervasive developmental disorder, intellectual disability, sensory integration disorder, gastroparesis, and hypotonia presented to our genetics clinic. She had negative karyotype by parental report but no other genetic testing performed previously. SNP microarray analysis revealed a complex genotype including 8.4 Mb terminal mosaic duplication on chromosome 3 (3p26.3->3p26.1) with the distal 5.7 Mb involving two parental haplotypes and the proximal 2.7 Mb involving three parental haplotypes, and a 6.1 Mb terminal mosaic deletion on chromosome 12 (12p13.33->12p13.31) with no evidence for a second haplotype. Adjacent to the mosaic deletion is an interstitial mosaic copy-neutral region of homozygosity (1.9 Mb, 12p13.31). The mother of this individual was confirmed by chromosome analysis and FISH that she carries a balanced translocation, t(3;12)(p26.1;p13.31).ConclusionTaken together, the proband, when at the stage of a zygote, likely carried the derivative chromosome 12 from this translocation, and a postzygotic mitotic recombination event occurred between the normal paternal chromosome 12 and maternal derivative chromosome 12 to “correct” the partial 3p trisomy and partial deletion of 12p. To the best of our knowledge, it is the first time to report the mechanism utilizing a combined cytogenetic and cytogenomic approach, and we believe it expands our knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling.

A rare familial rearrangement of chromosomes 9 and 15 associated with intellectual disability: a clinical and molecular study

BackgroundThere are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. Trisomy 9p is the fourth most frequent chromosome anomaly with a clinically recognizable syndrome often accompanied by intellectual disability. Here we report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability.Case presentationWe characterise a supernumerary derivative chromosome 15: 47,XY,+der(15)t(9;15)(p21.2;q13.2), likely resulting from 3:1 malsegregation during maternal gametogenesis. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. The child’s magnetic resonance imaging showed changes in brain volume and in structural and functional connectivity revealing phenotypic changes caused by the presence of the extra chromosome material, whereas the mother’s brain MRI was normal. Sequence analyses of the microdissected der(15) chromosome detected two breakpoint regions: HSA9:25,928,021-26,157,441 (9p21.2 band) and HSA15:30,552,104-30,765,905 (15q13.2 band). The breakpoint region on chromosome HSA9 is poor in genetic features with several areas of high homology with the breakpoint region on chromosome 15. The breakpoint region on HSA15 is located in the area of a large segmental duplication.ConclusionsWe discuss the case of these phenotypic and brain MRI features in light of reported signatures for 9p partial trisomy and 15 duplication syndromes and analyze how the genomic characteristics of the found breakpoint regions have contributed to the origin of the derivative chromosome. We recommend MRI for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes.

Goyal-Naqvi Syndrome (Concurrent Trisomy 10p and Terminal 14q Deletion): A Review of the Literature.

Goyal-Naqvi syndrome (GNS) is a newly documented clinical entity that comprises trisomy 10p and terminal 14q deletion, though trisomy 10p and terminal 14q deletion have been discovered as distinct conditions in 1974 and 1997, respectively. Nevertheless, to date, the total number of reported cases of each of these conditions is estimated to be in double digits. Both manifest as a constellation of features like craniofacial dysmorphism, hypotonia, intellectual impairment and global developmental delay. Characteristic facies include protruded forehead, hypertelorism, epicanthic folds, down slanting palpebral fissures, flat nasal bridge, long philtrum, thin upper lip, carp-shaped mouth, retro-micrognathia and low set ears. Besides, trisomy 10p is strikingly associated with clinodactyly and camptodactyly which aids in clinical diagnosis, apart from other musculoskeletal deformities like hip dysplasia and pes planus. Intersex conditions have been found to commonly co-exist. As other systems also display involvement frequently, trisomy 10p is a discernible multiple congenital anomalies/mental retardation (MCA/MR) syndrome. On the other hand, with terminal 14q deletion, increased risk of certain types of cancer was predicted as specific tumor suppressor genes are lost in the deletion and thus, screening was recommended. Genetic workup using techniques like fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and chromosomal microarray-based comparative genomic hybridization (CGH) was found to be helpful in diagnosis of trisomy 10p and 14q deletion. Prenatal diagnosis of these conditions has been well documented too. Intrauterine growth retardation has been observed to be related to trisomy 10p. There is a paucity of literature on the management of children diagnosed with trisomy 10p or with terminal 14q deletion. Although management of a child diagnosed with concomitant occurrence of trisomy 10p and terminal 14q deletion by a multidisciplinary approach emphasizing physiotherapeutic intervention has shown remarkable improvement in motor skills, the care of children diagnosed with these genetic aberrations needs further investigation. Documentation of more such cases will help to expand phenotypic spectrum for early identification and to delineate natural history for a life span approach. Early identification and intervention facilitate tapping of the maximum neuroplastic potential for better neurodevelopmental outcomes. We present a review of current literature on this novel syndrome to identify gaps in knowledge to build future research.