Holoprosencephaly in Patau Syndrome / Holoprosencefalia na Síndrome de Patau

ABSTRACT Objective: To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies. Case description: This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis. Comments: Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.

RESUMO Objetivo: Avaliar sinais radiológicos (gestacionais e perinatais) e neonatais de paciente com síndrome de Patau e holoprosencefalia semilobar, assim como relatar a associação de ambas as patologias. Descrição do caso: Trata-se de um relato de recém-nascido do sexo feminino a termo, que apresentou trissomia do cromossomo 13 e holoprosencefalia semilobar, com fusão talâmica e ventrículo cerebral único, além de várias outras alterações que pioraram o prognóstico da paciente. Comentários: A trissomia do cromossomo 13 é um defeito genético que caracteriza um conjunto de sintomas que compõem a Síndrome de Patau. Nesta síndrome, é comum o acometimento cardiovascular, urogenital, do sistema nervoso central, da estrutura facial e da capacidade intelectual, além de falhas na formação dos membros, como diminuição no comprimento do úmero, fêmur, polidactilia, hipotelorismo e baixa implantação das orelhas. Estima-se, no entanto, que a holoprosencefalia apresente-se nesse grupo de malformações congênitas apenas em 24 a 45% dos casos.

Cromosoma 13 en anillo / Ring chromosome 13

Resumen Introducción: El cromosoma 13 en anillo es una alteración citogenética infrecuente, clínicamente caracterizada por presentar retraso del crecimiento, del desarrollo psicomotor y déficit cognitivo, además de microcefalia, dismorfia facial, alteraciones genitales e hipoplasia del pulgar. Caso clínico: Paciente de 8 meses de edad evaluado por presentar talla baja, retraso del desarrollo psicomotor, microcefalia, dismorfia facial, hipospadias peneoescrotales e hipoplasia de pulgar. Se evidenció lisencefalia, hipoacusia neuroconductiva del lado derecho y comunicación interauricular tipo ostium secundum pequeña. El estudio citogenético del paciente mostró 46, XY, r (13) en 30 células analizadas. Conclusiones: Se resaltan los hallazgos clínicos que pueden orientar el diagnóstico de esta alteración cromosómica estructural infrecuente, destacando, además, la evaluación médica interdisciplinaria requerida y el adecuado asesoramiento genético familiar.

Abstract Background: Ring chromosome 13 is an infrequent cytogenetic disorder clinically characterized by growth and psychomotor development retardation, cognitive deficit, microcephaly, facial dysmorphism, genital alterations and thumb hypoplasia. Case report: A 8-month-old patient was evaluated for presenting short stature, psychomotor development delay, microcephaly, facial dysmorphism, penoscrotal hypospadias and thumb hypoplasia. Lissencephaly, neuroconductive hearing loss on the right side and small ostium secundum interatrial communication were evident. The cytogenetic study of the patient showed 46, XY, r (13) in 30 cells analyzed. Conclusions: Clinical findings that can guide the diagnosis of this infrequent structural chromosomal alteration are highlighted, as well as the interdisciplinary medical evaluation required and adequate family genetic counseling.

Case Report of Ring Chromosome 13: 46,xx.r(13)(p13q34)/46,xx,dicr(13;13)(p13q34;p13q34).

Aims: To report a case of ring chromosome 13 in a female child. Presentation of Case: Female, Caucasian, born in Southeast of Brazil, 6 years old. Born by cesarean section, the physical examination at 6 years and 1 month old has shown: weight of 19.100 grams and 105 centimeters tall, developmental delay, bushy eyebrows, epicanthic folds and broad nasal bridge, cardiovascular and respiratory systems were normal and no abnormalities in the limbs. Chromosome analysis was performed by GTG banding of peripheral blood and the karyotype was 46,XX,r(13)(p13q34)[97]/46,XX,dic r(13;13)(p13q34;p13q34) [3]. Analysis of 100 metaphases following G-banding revealed 97% cells with a ring chromosome 13,3% with dicentric ring chromosome of two 13s. Aneuploidy was not detected. Her parents had a normal karyotype. Discussion: Some researchers relate the clinical presentation of ring chromosome 13 with the extension of the deleted chromosomal region and instability. Others suggested that phenotypes of patients can be categorized in groups, according to the breakpoint on 13q. Conclusion: The classification of cases in groups based on breakpoints and chromosomal instability is still inaccurate, with variable phenotypes. Thus, the analysis of a greater number of cases and molecular analysis are important to establish more precise correlation between genotype and phenotype.

A Case of Sinusoidal Hemangioma with Lipoma

Sinusoidal hemangioma is a distinctive subset of a group of lesions known collectively as cavernous hemangiomas. Clinically, it develops in adults, predominantly females, and presents as a solitary, painless, bluish, deep dermal or subcutaneous nodule. Lipoma is the most common benign soft tissue tumor. Lipoma is distinguished from sinusoidal hemangioma on both clinical and histological grounds. Several studies have suggested that adipocytes originate from perivascular cells during adipogenesis. Angiogenic cytokines released by adipocytes play a role in the vasoproliferative response. The rearrangement or loss of chromosome 13 can also be associated with hemangioma. However, no previous cases of sinusoidal hemangioma have been associated with benign tumors like lipoma. Here, we describe an unusual case of sinusoidal hemangioma that occurred together with a lipoma on the right upper arm of a 43-year-old male.

Myelomatous Pleural Effusion: A Case Series in a Single Institution and Literature Review / 대한진단검사의학회지

BACKGROUND: Myelomatous pleural effusion (MPE) is rare in myeloma patients. We present a consecutive series of patients with MPE in a single institution. METHODS: We retrospectively reviewed the medical records of 19 patients diagnosed with MPE between 1989 and 2008 at the Asan Medical Center. Diagnoses were confirmed by cytologic identification of malignant plasma cells in the pleural fluid. RESULTS: Our patients showed dominance of IgA (36.8%) and IgD (31.6%) subtypes. Of 734 myeloma patients, the incidence of MPE was remarkably high for the IgD myeloma subtype (16.7%), compared to the other subtypes (1.4% for IgG and 4.6% for IgA). At the time of diagnosis of MPE, elevated serum beta2-microglobulin, anemia, elevated serum lactate dehydrogenase, and elevated creatinine levels were found in 100%, 89.5%, 83.3%, and 57.9% of the patients, respectively. Approximately one-third (31.3%) of the patients had adenosine deaminase (ADA) activities in their pleural fluid exceeding the upper limit of the reported cutoff values for tuberculous pleural effusion (55.8 U/L). Chromosome 13 abnormality was seen in 77.8% of the tested patients. The median survival period from the development of MPE was 2.8 months. CONCLUSIONS: Patients with MPE have aggressive clinical and laboratory characteristics. The preponderance of IgD myeloma in MPE patients is a noteworthy finding because IgD myeloma is a rare subtype. Elevated ADA activity in the pleural fluid is also noteworthy, and may be helpful for detecting MPE. Physicians treating myeloma patients should monitor the development of MPE and consider the possibility of a worse clinical course.

Chromosome 13 abnormalities and multiple myeloma / 白血病·淋巴瘤

With the development of FISH and other technique, the detection rate of chromosome abnormalities in multiple myeloma (MM) were increased. Chromosome 13 abnormalities is most common feature (about 50 %). The tumor suppressor gene and micro RNA on chromosome 13 play an important role on pathogenesis of MM. In the last decade, it is widely believed that chromosome 13 abnormalities is independent poor prognosis factor, but the recent more studies conform that its prognosis value is dependent on the other chromosome abnormalities. It is found that the new drugs such as bortezomib appear to reverse the poor prognosis conferred by chromosome 13 deletion.

Diagnóstico molecular de cromosomopatías fetales en Costa Rica / Molecular diagnosis of fetal chromosomal defects in Costa Rica

En Costa Rica, el diagnóstico de anomalías cromosómicas fetales se realiza solo mediante el análisis citogenético convencional de cromosomas obtenidos de cultivos celulares. Además de que la espera por los resultados puede ser larga, con alguna frecuencia fracasa el cultivo, por contaminación o por mala calidad de la muestra, o las figuras mitóticas no se pueden analizar, por lo que es necesario disponer de una metodología sencilla y barata, para obtener un diagnóstico prenatal rápido y fiable de trisomía 21, 18 ó 13, en embarazos de alto riesgo genético sometidos a amniocentesis o cordocentesis. Métodos: Se diseñaron tres PCRs multiplex para amplificar cuatro distintas repeticiones cortas en tándem, de cada uno de los cromosomas 21, 18 y 13. Se colectaron 93 muestras (88 líquidos amnióticos y 5 sangres fetales), recibidas en el laboratorio entre 2006 y 2008, con solicitud de análisis cromosómico. Los resultados de la reacción en cadena de la polimerasa cuantitativa fluorescente, fueron comparados con el cariotipo obtenido de las mismas muestras para demostrar la fiabilidad del ensayo. Resultados: Para este grupo de datos, la exactitud del ensayo fue del 100 por ciento y se consiguió obtener resultados en 48 horas. Se logró realizar el análisis de repeticiones cortas en tándem en el 77 por ciento de las muestras en las que no se pudo obtener crecimiento celular. Conclusión: La reacción en cadena de la polimerasa cuantitativa fluorescente demostró ser una metodología sencilla, fiable y rápida, por lo que podría convertirse en una herramienta complementaria del análisis cromosómico convencional. La obtención de resultados rápidos en casos de diagnóstico prenatal podría disminuir el periodo de ansiedad parental por la espera de los resultados, así como permitir un mejor abordaje terapéutico de los fetos afectados.

In Costa Rica, the diagnosis of chromosomal fetal anomalies is realizedonly by conventional cytogenetic analysis of chromosomes obtained from cellular cultures. The waiting for the results can be long. Moreover with some frequency culture fails due tocontamination or bad quality of the sample or they cannot be analyzed. This makes it necessary to have a simple and cheap methodology to obtain an accurate and rapid fetal diagnosis of trisomy 21, 18 or 13, in pregnancies of high genetic risk submitted to amniocentesis or cordocentesis. Materials and methods: Three multiplex PCRs were designed to amplify four different short tandem repeats of each of the chromosomes 21, 18 and 13. There were collected 93 samples (88amniotic fluids and 5 fetal bloods), received in the laboratory between 2006 and 2008 with request ofor chromosomal analysis. The results of the quantitative fluorescent PCR werecompared with the obtained cariotype of the same samples to stablish the accuracy demonstrate the reliability of the assay. Results: Accuracy of the assay was 100% and it was possible to obtain results within 48 hours.STRs analysis could be made in 77% of the samples where the cellular culture could not be done. Conclusion: The quantitative fluorescent PCR demonstrated to be a simple, accurate and rapid methodology, from what it might turn into a complementary tool of the chromosomal conventional analysis. The securing of rapid results in cases of antenatal diagnosis might diminish the period of anxiety parental for the waiting of the results, as well as to allow a better therapeutic management of the affected fetuses.

A case of mosaic ring chromosome 13 syndrome / 소아과

The clinical features of ring chromosome 13 include mental and growth retardation, CNS anomalies, facial dysmorphism, cardiac defects, genital malformations, limb anomalies, skeletal deformities and anal malformations. Although many cases of ring chromosome 13 have been reported worldwide, only 6 cases have been reported in Korea, and the latter cases were not mosaic but pure ring chromosome 13. Here we report a case with mosaic ring chromosome 13. The baby boy was born at 37 weeks of gestation by induced vaginal delivery due to intrauterine growth restriction (IUGR). He was the second baby of a 28-year-old hepatitis B carrier mother and a 32-year-old father. There was no family history of chromosomal anomalies. The baby was a symmetric IUGR with a birth weight of 1,860 g, length of 44.8 cm, and head circumference of 29.4 cm. The physical examination revealed microcephaly, trigonocephaly, flat occiput, large ears, short neck and dysmorphic facial features, including microophthalmia, hypertelorism, antimongoloid slanting palpebral fissures, a flat nasal bridge, and micrognathia. The karyotype of this patient performed by peripheral blood lymphocytes was 46,XY,r(13)(p13q34)/45,XY,-13/46,XY,dic r(13;13)(p13q34;p13q34). The baby showed failure to thrive, hypotonia, and developmental delay. We report the first case of mosaic ring chromosome 13 in a male baby in Korea and compare this case with other Korean cases of non-mosaic ring chromosome 13.

A Case of Generalized Vitiligo Associated with Interstitial Deletion of Chromosome 13q

No abstract available.

A Case of 13q- Syndrome with Arthrogryposis Multiflex Congenita

13q- syndrome is a rare genetic disorder characterized by psychomotor retardation, hypotonia, microcephaly, retinoblastoma, ptosis and coloboma. Facial and congenital heart anomalies are also found and about 60% of males have genital and anorectal malformations. We report a case of 13q- syndrome male infant with many of afore mentioned features including imperforate anus, penoscrotal inversion, dolichocephaly, large low set ears, micrognathia, bifid scrotum with arthrogryposis, diagnosed by chromosomal analysis using synchronized high resolution G-banding technique which revealed of 46, XY, del(13) (q22) in all 20 metaphases. Echocardiogram and kidney sonogram were normal.

A case of de novo ring (13) chromosome with deletion 13q32.2-->qter / 대한산부인과학회잡지

We report a case of ring chromosome 13 with a distal deletion of 13q32.2-->qter observed in a fetus who was referred to our institution at term due to severe growth restriction and multiple congenital malformations on ultrasonographic examination.This boy was born by vaginal delivery at 39 weeks in gestation. His weight, head circumference and height were less than the 3 percentile of gestational age. Apgar score was 7 at 1 minute and 9 at 5 minutes. He showed microcephaly, large forehead, low set ears, hypertelorism, flat nasal bridge, and micrognathia. The genitalia was ambiguous, showing severe hypoplasia of the penis. The anus was ectopic, displaced anteriorly from its normal position but with a normal opening and function. Neurologic examination was normal. Echocardiogram done at 2 weeks of life showed a persistent foramen ovale and a ventriculoseptal defect (type II) with increased pulmonary hypertension. MRI examination of the brain showed poorly demarcating corpus callosum suspecting agenesis of corpus callosum. Also, cerebellar vermis was small and hypoplastic, mimicking a variant form of Dandy-Walker malformation. MRI of the pelvis showed a tubular structure in pelvic cavity, suspicious of uterine remnant, between urinary bladder and rectum, and a inguinal hernia was noted in the left side. In the abdominal cavity enlarged adrenal glands were noted, and hormonal study showed elevated 17-alpha-OH-progesterone (168.9 ng/ml) with normal 17-KS and 17-OHCS levels. Gastrointestinal and urogenital system were otherwise normal. Cytogenetic analysis of the parents were both normal but the newborn showed 46, XY, r (13), de novo, with deletion points q32.2-->qter. Our findings are in line with previous reports about chromosome 13 deletions, in which loss of the "critical point" leads to major malformations like brain anomalies and ambiguous genitalia.

A Case of Terminal Deletion of Chromosome 13q / 대한산부인과학회잡지

The 13q deletion syndrome was described firstly by Allderdice et al. in 1969. Common findings include fetal growth restriction, microcephaly, other central nervous system malformations, eye abnormalities, characteristic facial appearance, congenital heart defects, gastrointestinal anomalies, vertebral, limb, and perineal defects, and varying degrees of mental retardation. We report a case of terminal deletion of chromosome 13q. Conventional cytogenetic result from amniocytes was 46,XY,del(13)(q32). The prenatal ultrasonographic findings were fetal growth restriction, oligohydramnios, microcephaly, ventriculomegaly and clubfoot. Gross anomalies after delivery included microcephaly, low set ears, absent thumbs, club foot, partial syndactyly of 4th and 5th toes, ambiguous genitalia, and imperforate anus. In addition to characteristic features of 13q terminal deletion, cleft lip and palate was found in our case. Cytogenetic abnormality probably results from phenotypically normal mother, whose karyotype was 46,XX,inv(3)(p26q13.1),t(13;20)(q32;p13) from lymphocytes.

The 13q14 Deletion in Retinoblastoma

Retinoblastoma is the most common intraocular malignant tumor in children. Retinoblastoma is divided two groups, hereditary and non-hereditary. Hereditary retinoblastoma is relakd to chormosomal abnormalities. By banding technique of somatic chromosome in retinoblastoma, deletion of chromosome 13q14 is found, but it has not been reported domestically. We experienced two cases of retinoblastoma with chromosome 13q14 deletion.