Tetrasomy 9p syndrome in a Filipino infant

@#Tetrasomy 9p syndrome is a rare chromosomal abnormality syndrome whose most common features include hypertelorism, malformed ears, bulbous nose and microretrognathia. These features present as a result of an additional two copies of the short arm of chromosome 9. Here we present a neonate with characteristic facial features of hypertelorism, downslanted palpebral fissure, bulbous nose, small cupped ears, cleft lip and palate, and downturned corners of the mouth. Clinical features were consistent with the cytogenetic analysis of tetrasomy 9p. In general, clinicians are not as familiar with the features of tetrasomy 9p syndrome as that of more common chromosomal abnormalities like trisomies 13, 18, and 21. Hence, this case re-emphasizes the importance of doing the standard karyotyping for patients presenting with multiple congenital anomalies. Also, this is the first reported case of Tetrasomy 9p syndrome in Filipinos.

Isochromosome Mosaic Turner Syndrome: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#Turner syndrome (TS) with an isochromosome mosaic karyotype 45,X/46,X,i(X) (q10) is an unusual variant, with only an 8-9% prevalence among women with TS based on international studies and 15% of all TS in the Philippines. Clinical features are atypical and any case should be investigated to detect potential complications.A 20-year-old female came in due to amenorrhea and alopecia. Physical examination revealed short stature, cubitus valgus and Tanner Stage 1 pubic hair and breast development. Transrectal ultrasound revealed absent ovaries and infantile uterus. Hormonal evaluation revealed hypergonadotropic hypogonadism. Bone aging was that of a 13-year-old for females with non-fusion of epiphyseal plates. Cytogenetic study revealed 45,X [37]/46, X, i (X) (q10)[13]. This is consistent with a variant Isochromosome Mosaic Turner Syndrome (IMTS). She was screened for medical complications. Audiogram and two-dimensional echocardiography were unremarkable. She has dyslipidemia and was given a statin. She has subclinical hypothyroidism with positive test for anti-thyroglobulin antibody. Her intelligence quotient (IQ) was below average. She received conjugated estrogen and progesterone that patterned the hormonal changes in a normal menstrual cycle. On the third week of hormonal therapy, she developed breast mound and on the fourth week, she had her first menstrual period. Her alopecia spontaneously resolved. The case is a variant of Turner Syndrome requiring supportive, medical and psychological care

Cytogenetic and molecular genetic analysis of the amniotic fluid cells of a fetus with pseudodicentric isochromosome 22 resulting in partial tetraploidy of 22q / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To diagnose chromosomal abnormalities in amniotic fluid cells by combining karyotyping and single nucleotide polymorphism array (SNP-array) analysis, and to explore the application of SNP-array in routine clinical practice.</p><p><b>METHODS</b>Conventional G banding was used to karyotype a fetal amniotic fluid sample and the corresponding peripheral blood samples from the parents, followed by SNP-array analysis of the fetal genomic DNA from the amniotic fluid.</p><p><b>RESULTS</b>The karyotype of the amniocytes was 47, XX, +mar. The marker chromosome was further identified as psu idic (22) (q11.2) by SNP-array analysis, revealing tetraploidy of a 1.7 Mb fragment in 22q11.1-q11.2 interval that involves the critical region for Cat eye syndrome.</p><p><b>CONCLUSION</b>A rare chromosomal abnormality was identified by combining conventional G banding and SNP-array. The high resolution SNP-array could provide more detailed information for determining the origin of chromosomal abnormalities.</p>

Isocromosoma Xq en mosaico y microduplicación 17pl3. 3pl3. 2 en una paciente con síndrome de Turner y catarata congénita / Mosaic isochromosome Xq and microduplication 17p13. 3p13. 2 in a patient with Turner syndrome and congenital cataract

La combinación del síndrome de Turner con otros trastornos genéticos, como la catarata congénita, ha sido reportada. Sin embargo, su asociación con una forma de catarata nuclear congénita con herencia autosómica dominante y penetrancia incompleta no ha sido reportada previamente en la literatura. Tampoco existen reportes de su presentación junto con rearreglos en el cromosoma 17. A continuación, presentamos el excepcional caso de una paciente con una constelación de anomalías mayores y menores, diagnosticada con síndrome de Turner en mosaico por isocromosoma Xq, asociado a una microduplicación 17p13.3p13.2, quien además presenta catarata nuclear congénita bilateral de herencia autosómica dominante con penetrancia incompleta. Se realiza una revisión acerca del origen y la causa de estas alteraciones genéticas y una aproximación a la hipótesis de la patogénesis de la asociación de dos de estos trastornos genéticos en una misma paciente.

The combination of Turner syndrome with other genetic disorders such as congenital cataract has been reported, but its association with a congenital form with autosomal dominant inheritance and incomplete penetrance has not been previously reported in the literature. There are no reports on its presentations with rearrangements on chromosome 17. We report the exceptional case of a 20 months old girl with a constellation of major and minor anomalies, diagnosed with mosaic Turner syndrome by isochromosome Xq associated with a microduplication 17p13.3p13.2, who also had bilateral congenital nuclear cataract autosomal dominant with incomplete penetrance. We reviewed in the literature the origin and cause of these genetic alterations and we provided an approach to the hypothesis of the pathogenesis of the association of two of these genetic disorders in the same patient.

A Novel Case of Extreme Thrombocytosis in Acute Myeloid Leukemia Associated With Isochromosome 17q and Copy Neutral Loss of Heterozygosity

No abstract available.

A Case of Pentasomy 21 With Two Isochromosome 21s in Acute Megakaryoblastic Leukemia Associated With Down Syndrome

No abstract available.

Isochromosome 1q in Childhood Burkitt Lymphoma: The First Reported Case in Korea

No abstract available.

Bone marrow hypoplasia, isochromosome 8q and deletion of chromosome 6q preceding B-cell lymphoma

No abstract available.

A case report of prenatally diagnosed tetrasomy 18p

Tetrasomy 18p, one of the most commonly observed isochromosomes, consists of two copies of the p arms on chromosome 18[i(18p)]. It is known as a de novo occurrence of non-disjunction or centromeric mis-division during meiosis II in the vast majority of cases. It has a prevalence of 1/140,000-180,000 live births and affects both genders equally. A 28-year-old woman was referred at 33+2 weeks gestation to rule out fetal congenital heart disease. Her prenatal ultrasonography showed intrauterine growth retardation, cardiomegaly, and imperforate anus. Doppler ultrasonographic finding showed fetal anemia. Tetrasomy 18p was confirmed by conventional karyotyping and fluorescence in situ hybridization. Because of its very low prevalence rate, only several cases of tetrasomy 18p has been reported worldwide and it has not yet been reported in Korea before. Therefore, we report a case of prenatally diagnosed tetrasomy 18p.

A Case of Acute Myeloid Leukemia with Bone Marrow Basophilia and Dysmegakaryocytic Hyperplasia with Isochromosome 17q as a Sole Cytogenetic Abnormality: A Clinical Study with Literature Review

A new clinico-pathological entity in which isochromosome 17q is the sole abnormality has been reported in myelodysplastic syndrome and in myeloproliferative neoplasm with an aggressive course; In particular, myelodysplastic syndrome with the isolated i(17)(q10) chromosome has the unique features of male sex, severe anemia, dysmegakaryocytic hyperplasia, increased micromegakaryocytes, basophilia, eosinophila and high risk for progression to acute myeloid leukemia (AML). However, the isolated i(17)(q10) is occurring at a relatively low frequency in de novo AML, and only a few reports are available in the literature about the clinical features and molecular characteristics of the isolated i(17)(q10) in AML. Herein, we report both the clinico-pathological features and the results of high resolution single nucleotide polymorphism (SNP) array analysis in a case of AML with i(17)(q10) as the sole cytogenetic abnormality. This case showed marrow findings of basophilia and dysmegakaryocytic hyperplasia and aggressive clinical outcome and these findings were suggestive of the presence of underlying myelodysplastic syndrome. The breakpoint of i(17)(q10) was located within 17p11.2 sub-band, which is known as a genetically highly unstable region presenting a unique genomic architectural features of low copy repeats (LCRs); thus, LCRs within 17p11.2 might lead to genomic instability and facilitate somatic genetic rearrangements such as i(17) (q10) and could play an important pathogenetic role in presenting unique clinico-pathologic features as well as in tumor development and disease progression.

Recurrent isochromosome 21 and multiple abnormalities in a patient suspected of having acute myeloid leukemia with eosinophilic differentiation -- a rare case from South India / 癌症

Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia(Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.

Development of Acute Megakaryoblastic Leukemia with Isochromosome (12p) after a Primary Mediastinal Germ Cell Tumor in Korea

The association of hematological malignancies with a mediastinal germ cell tumor (GCT) is very rare. We report one case of a young adult male with primary mediastinal GCT who subsequently developed acute megakaryoblastic leukemia involving isochromosome (12p). A 25-yr-old man had been diagnosed with a mediastinal GCT and underwent surgical resection and adjuvant chemotherapy. At 1 week after the last cycle of chemotherapy, his peripheral blood showed leukocytosis with blasts. A bone marrow study confirmed the acute megakaryoblastic leukemia. A cytogenetic study revealed a complex karyotype with i(12p). Although additional chemotherapy was administered, the patient could not attain remission and died of septic shock. This case was definitely distinct from therapy-related secondary leukemia in terms of clinical, morphologic, and cytogenetic features. To our knowledge, this is the first case report of a patient with mediastinal GCT subsequently developing acute megakaryoblastic leukemia involving i(12p) in Korea.

Report of ten cases of hematologic malignancies with idic(20q-) and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and molecular cytogenetic features of hematologic malignancies with idic(20q-).</p><p><b>METHODS</b>The clinical data of 10 patients with idic (20q-) were analyzed. Karyotyping analysis was carried out with R banding technique. A CEP20 probe was used to perform single-color fluorescence in situ hybridization (FISH). A subtelomeric probe for 20q and a locus-specific probe for 20q12 were used to perform dual-color FISH. The literatures of hematologic malignancies with idic(20q-) were reviewed.</p><p><b>RESULTS</b>Of the 10 cases, 2 were diagnosed as acute erythroid leukemia, 1 primary myelofibrosis, 3 myelodysplastic syndromes (MDS) and 4 highly suspected (HS-MDS). Karyotype analysis showed that one of the normal chromosome 20 allele was substituted by one or two metacentric isochromosomes smaller than the normal one in all 10 cases. It was confirmed to be der(20)del(20)(q11q13)idic(20)(p11), i.e., idic(20q-) by FISH assay. Partial cells in 2 of the 10 cases had 20q- as the sole karyotypic anomaly.</p><p><b>CONCLUSION</b>Idic(20q-) results from a pre-existing del(20q) and is strongly associated with MDS and acute erythroid leukemia. Idic(20q-) as a recurrent cytogenetic abnormality is helpful for diagnosing HS-MDS in patients with cytopenia but only slight or absent dysplasia.</p>

Isocromosoma 18q en mosaico: caso clínico / Mosaic Isochromosome 18q: case-report

Background: The Isochromosome 18q and chromosome 18 short arm deletion (18p-) constitute structural anomalies that are reported with certain frequency in the literature. However, the association of both abnormalities in a patient is very uncommon. Objective: Description of a clinical case of Isochromosome 18 with emphasys in the few phenotypic manifestations. Case-report: Female infant 18 months-old, with short stature, minor dysmorphic features and a slight psychomotor developmental delay, whose chromosomal study in peripheral blood showed a chromosomal mosaicism with two cell lines: chromosome 18 long arm isochromosome and deletion of chromosome 18 short arm. The chromosomal analysis of both parents did not show numerical neither morphological alterations. Discussion: This case illustrates the importance of requesting a karyotype in patients with small stature, dysmorphic features and/or malformations. The patient clinical features are compared with other similar cases described in the literature. The coexistence of both structural abnormalities (mosaicism) is extremely uncommon.

Introducción: El Isocromoma 18q y la deleción del brazo corto del cromosoma 18 (18p-), son anomalías estructurales que se reportan con cierta frecuencia en la literatura. Sin embargo, la asociación de ambas alteraciones en una misma paciente es muy infrecuente. Objetivo: Descripción de un caso clínico de Isocromosoma 18 con énfasis en la escasas manifestaciones fenotípicas. Caso Clínico: Lactante femenino de 18 meses de edad portador de talla baja, dismorfias menores y un leve retraso del desarrollo sicomotor, cuyo estudio cromosómico en sangre periférica mostró un mosaico compuesto por un isocromosoma del brazo largo del cromosoma 18 y otro cromosoma 18 con deleción del brazo p. El análisis cromosómico de ambos padres no mostró alteraciones numéricas ni morfológicas. Discusión: Este caso ilustra la importancia de solicitar un cariograma en pacientes con talla baja, dismorfias y/o malformaciones. Se describen las malformaciones encontradas y se compara con otros casos similares descritos en la literatura. La alteración estructural en mosaico reportada es sumamente infrecuente.

Un caso de sirenomelia con cariotipo isocromosoma 18q en mosaico / Sirenomelia with isochromosome 18q mosaicism: a clinical case

La sirenomelia es una patología muy rara, siendo su incidencia aproximadamente de 1 cada 60.000 nacidos vivos, en la que los miembros inferiores se encuentran fusionados. El trastorno en el desarrollo del blastema caudal axil posterior sería en la tercera semana y probablemente debido a una alteración del desarrollo vascular. Es frecuente la asociación con malformaciones cardiovasculares, gastrointestinales, respiratorias y alteraciones del tubo neural. Se reporta un caso de una recién nacida con sirenomelia cuya madre fue una primigesta de 23 años, con antecedentes de epilepsia en tratamiento con fenitoína sódica durante dos años. En el seguimiento ecográfico se determinó la malformación como sirenomelia tipo Vil con presencia de riñón poliquístico bilateral, cardiopatía congénita, mielomeningocele, además de oligoamnios severo. Fallece al nacer. Se observó un cariotipo en mosaico de tres líneas celulares: 46,XX,i(18)(q10)[9]/46,XX,-18,+mar[12]/46,XX[4]. Existe asociación entre el uso de terapia anticonvulsivante y el riesgo de malformaciones congénitas. Sin embargo, la literatura no establece una asociación entre este tipo de medicamentos y alteraciones cromosómicas, no pudiéndose establecer una relación causal. Consideramos importante reportar la coexistencia de esta alteración y el fenotipo sirenomélico.

Sirenomelia is a very rare pathology, being its incidence approximately of 1 each 60,000 live born, in that the inferior members are fused. The upheaval in the development of axil caudal blastema would be in the third week and probably due to an alteration of the vascular development. They are frequent associated cardiovascular, gastrointestinals, and respiratory malformations and alterations of the neural tube. A case of sirenomelia in a patient of 23 years old is reported, with antecedent of epilepsy in phenitoyn treatment during two years. In the echographic pursuit the malformation was determined as sirenomelia type Vil with presence of bilateral poliquistic kidney, congenital cardiopathy, mielomeningocele, and severe oligoamnios. The infant die at born. Kariotype displayed a mosaic of three cellular lines: 46,XX,i(18)(q10)[9]/46,XX,-18,+mar[12]/46,XX[4]. An association established between the use of the anticonvulsivant therapy and the risk of congenital malformations exists. Nevertheless, literature does not establish an association between this type of drugs and chromosomic alterations, not being able to establish a causal relation. It is important, even so, to report the coexistence of this alteration and the sirenomelic phenotype.

A case of acute promyelocytic leukemia with double ider (17q-) / 中国实验血液学杂志

This study reported a relapsed case of acute promyelocytic leukemia with complex chromosomal aberrations of double ider (17q-) and explored its laboratory and clinical features. Immunophenotypic analysis was performed by multiparameter flow cytometry. Conventional cytogenetics was used for karyotyping analysis. Fluorescence in situ hybridization (FISH) and multiplex fluorescence in situ hybridization (M-FISH) were also used to identify the chromosomal aberrations. The results demonstrated that karyotype was 47, XY, 1p-, 15q+, ider (17q)x2, FISH showed five fusion signals in a same interphase cell, and M-FISH confirmed the abnormalities. Immunophenotypic analysis showed positive expression of CD13 and CD33, while no expression of CD34, HLA-DR, or T, B lymphocyte markers. In conclusion, double ider (17q-) is a rare additional abnormality in APL patients; combination of FISH with M-FISH techniques is a reliable way to identify such complicated chromosomal aberrations.

Constitutional tetrasomy 18p.

We present here the first case of constitutional tetrasomy 18p from India. A 3 year old female with developmental delay and dysmorphic features revealed 47,XX,+mar karyotype. The small meta-centric marker chromosome was identified as i(18p) with m-FISH followed by m-BAND. Parents and a normal sibling of the proband revealed normal karyotype. There was history of mental retardation and dysmorphic features in four cases on paternal side; however, their karyotype was also normal.

A Case of Acute Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) / 대한진단검사의학회지

ider(9)(q10)t(9;22)(q34;q11.2) is an isochromosome for the long arm of a derivative chromosome 9 generated by a t(9;22), resulting from the deletion of the short arm of chromosome 9. It is known to be rarely observed in acute lymphoblastic leukemia (ALL) or lymphoblastic crisis transformed from chronic myelogenous leukemia. We herein describe a 26-year-old female patient with precursor B-cell ALL, cytogenetically characterized by ider(9)(q10)t(9;22). Fluorescence in situ hybridization analysis showed two ABL-BCR fusion signals on the derivative chromosome 9 and one BCR-ABL fusion signal on the derivative chromosome 22. Although a t(9;22) and a deletion of the short arm of chromosome 9 are known to be associated with a poor prognostic factor in acute lymphoblastic leukemia, a larger study is needed to determine the prognosis of ider(9)(q10)t(9;22) cases.

Identification of marker chromosomes by reverse painting fluorescence in situ hybridization and comparative genomic hybridization / 대한산부인과학회지

OBJECTIVE: Although marker chromosome is defined as an abnormal chromosome in which no part can be identified, derivative chromosomes with structural abnormalities of unknown origin are also called as marker chromosomes conventionally. The clinical significance of a marker chromosome is determined according to the origin of marker chromosome. In this study reverse painting fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) methods were employed to elucidate the origin of marker chromosomes in 5 clinical cases. METHODS: Reverse painting probes were generated from five copies of each marker chromosomes microdissected with micromanipulator, amplified with DOP-PCR, and labeled with fluorochromes. The probes were hybridized to normal metaphases. For CGH, normal control and patients' DNA were directly labeled with spectrum-red-dUTP and spectrum-green-dUTP by CGH nick translation kit, and hybridized to normal reference metaphases. The CGH images were captured with a computer controlled fluorescence microscope equipped with a CCD camera and analyzed by Cytovision workstation. RESULTS: Five marker chromosomes were identified as follows (1) derivative chromosome 15 inducing partial trisomy of 15pter->q21, (2) isochromosome of 18p causing 18p tetrasomy, (3) short arm of chromosome 5 causing 5p trisomy (4) small accessory chromosome originated from centromeric region of chromosome Xq11->q12 (5) der(17) with inverted duplication of the short arm of chromosome 17. In all cases the origin of each marker chromosomes were identified successfully with reverse painting FISH, and these results were concordant with the CGH profiles. CONCLUSION: Our results indicate that combined reverse painting FISH and CGH is a rapid, convinient and powerful tool to identify the origin of marker chromosomes and derivative chromosomes caused by various chromosome abnormalities such as translocation, duplication, deletion.

Clinical and experimental study of two cases of myelodysplastic syndromes with double isochromosome 20q- anomaly / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical and laboratory characteristics of two myelodysplastic syndromes (MDS) patients with double isochromosome 20q- anomaly.</p><p><b>METHODS</b>Bone marrow cell chromosome preparations were made with both direct method and short-term culture. Karyotype analysis was performed by R-banding technique, and dual-color FISH (fluorescence in situ hybridization) by using a 20q telomeric probe and a sequence-specific probe for 20q12.</p><p><b>RESULTS</b>The clinical and hematological findings were comparable with diagnosis of MDS. Karyotype analysis showed that both patients had double isochromosome 20q- anomaly: case 1 is 46, XX, der(20)? i(20q-) [6]/46, idem, der (6) i (6p) [1]/47, idem, +der (20)? i (20q-) [3]/47, idem, der(6)i (6p), +der(20)? i (20q-) [20]; case 2 is 45, XY, -7, der (20)? i (20q-) [17]/46, idem, +der(20) ? i(20q-) [3]. Two derivative chromosomes 20 were proved 20q isochromosomes with interstitial deletions by dual-color FISH in one patient.</p><p><b>CONCLUSIONS</b>Double isochromosome 20q- anomaly is a rare recurrent karyotype abnormality in MDS, and signals a poor prognosis.</p>