RESUMEN

BACKGROUND: Submucous cleft palate is a cleft of the secondary palate with low phenotypic gene expression. It can occur as an isolated malformation or associated with a syndrome that includes certain facial features and other vocal tract malformations. Velopharyngeal insufficiency (VPI) is rare in cases of non - syndromic occult clefts of the secondary palate (OSCSP). In contrast, syndromic OCSP has a high prevalence of VPI. VPI requires surgical treatment in the vast majority of cases. OBJECTIVE: To present a case of OSCSP with VPI after partial tonsillectomy and adenoidectomy (T & A) associated with facial features and other vocal tract malformations. A chromosomal abnormality (8q22.2 deletion) was demonstrated by cytogenetic testing. CASE PRESENTATION: Eight year old female with VPI following partial T & A. OSCSP was diagnosed. Complete T & A was performed in preparation for a pharyngeal flap. Pharyngeal flap surgery was customized according to findings of videonasopharyngoscopy (VNP) and multiplanar videofluoroscopy (MPVF). VPI was corrected without intraoperative or postoperative complications. CONCLUSION: The presence of multiple vocal tract malformations should be a red flag for suspecting a syndromic OSCSP. Surgical treatment of VPI in cases of OSCSP should be performed after complete T & A, Imaging procedures for assessing neck blood vessels and it should be customized according to imaging (VNP and MPVF) findings.

Asunto(s)

Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 8 , Fisura del Paladar/genética , Insuficiencia Velofaríngea/genética , Insuficiencia Velofaríngea/cirugía , Niño , Fisura del Paladar/complicaciones , Femenino , Humanos , Insuficiencia Velofaríngea/complicaciones

RESUMEN

Melanotic Xp11 translocation renal cancer is a rare category of MiTF/TFE3 neoplasms morphologically resembling Xp11 translocation renal cell carcinoma, Xp11 translocation perivascular epithelioid cell tumor, and melanoma. The diagnosis requires demonstration of TFE3 gene rearrangement, by either fluorescence in situ hybridization (FISH) at the Xp11.2 locus or by TFE3 immunohistochemistry. As cytology smears can be useful adjuncts in cytogenetic and molecular testing, we demonstrate TFE3 rearrangement by FISH analysis on cytologic smears in melanotic Xp11 translocation renal cancer. An 18-year-old girl presented with a large right renal mass. Intraoperative scrape smears were performed on suspicious aortocaval lymph nodes. A subset of smears was stained (Papanicolaou and DiffQuik). Morphologically, the neoplastic cells exhibited abundant clear vacuolated cytoplasm and moderate to marked nuclear pleomorphism. Unstained and destained smears were examined for TFE3 rearrangement by FISH. Positive TFE3 FISH results on formalin-fixed paraffin-embedded tissue correlated with the positive FISH findings of TFE3 gene rearrangement on cytologic smears. Therefore, the diagnosis of melanotic Xp11 translocation renal cancer was rendered. In Xp11 translocation associated neoplasms, FISH analysis on cytologic smears can be an efficient, accurate, and cost-effective method for evaluating TFE3 rearrangement.

Asunto(s)

Cromosomas Humanos X/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Melanoma/diagnóstico , Melanoma/patología , Translocación Genética , Adolescente , Análisis Citogenético , Femenino , Humanos , Coloración y Etiquetado

RESUMEN

We report a case of a small-cell variant of anaplastic large-cell lymphoma, with an unusual clinical presentation mimicking sepsis and a fulminant clinic course, in a 48-year-old Caucasian female. In this report, we discuss the diagnostic challenge, histopathologic features, and unique cytogenetic features of this case, in order to raise awareness of this rare presentation and emphasize the importance of meticulous peripheral smear examination and early bone marrow evaluation.

RESUMEN

Duplications of the SHH gene, an important developmental gene, are rare. Disruption of this gene produces a variable phenotype in humans from major anomalies to isolated facial defects. This is the first reported case of a maternally inherited 507 kb discontinuous chromosome 7q36.3 microduplication resulting in duplication of SHH and nearby enhancer sequences.

RESUMEN

Fewer than 100 patients with partial chromosome 2p trisomy have been reported. Clinical features are variable and depend on the size of the duplicated segment, but generally include psychomotor delay, facial anomalies, congenital heart defect, and other abnormalities. We report a 560.49 kb duplication of chromosome 2p in a 13 month-old male with hydrocephaly, ventricular septal defect, partial agenesis of the corpus callosum, and bilateral Wilms tumor. After discovery of bilateral renal masses at four months of age, the child underwent neoadjuvant chemotherapy followed by right radical nephrectomy that revealed triphasic Wilms' tumor. A needle core biopsy on one of two lesions on the left kidney also revealed Wilms tumor. A partial left nephrectomy revealed focally positive margins that necessitated left flank radiotherapy. The tumor karyotype was 46,XY,t(7;8)(q36;p11)[8]/46,XY [12] while his constitutional karyotype was 46,XY, suggesting that the t(7;8)(q36;p11) was associated with the malignancy. Single nucleotide polymorphism (SNP) chromosome microarray analysis of peripheral blood identified a maternally-inherited 560.49 kb chromosome 2p24.3 duplication that involved four OMIM genes: NBAS, DDX1, MYCNOS, and MYCN. SNP array analysis of the tumor revealed the same 2p24.3 duplication. At present, the now 5-year-old boy continues to do well without clinical or radiographic evidence of recurrent disease. This case is instructive because the child's health insurer initially denied authorization for chromosome microarray analysis (CMA), and it took more than one year before such authorization was finally granted. That initial decision to deny coverage could have had untoward health implications for this child, as the identification of constitutional MYCN duplication necessitated surveillance imaging for a number of pediatric malignancies associated with MYCN overexpression/dysregulation.

Asunto(s)

Anomalías Múltiples/genética , Neoplasias Renales/genética , Proteína Proto-Oncogénica N-Myc/genética , Tumor de Wilms/genética , Anomalías Múltiples/patología , Duplicación Cromosómica/genética , Cromosomas Humanos Par 2/genética , Humanos , Lactante , Cariotipificación , Neoplasias Renales/patología , Masculino , Análisis por Micromatrices , Polimorfismo de Nucleótido Simple , Trisomía/genética , Tumor de Wilms/patología

RESUMEN

Writing the recent history of a subject is notoriously difficult because of the lack of perspective and impartiality. One way to gain insight and understanding into the recent past of a discipline of knowledge is to consult directly the living practitioners who actually experienced first-hand the major changing circumstances in the discipline during the period under study. This article seeks to explore the most significant changes occurring in Western, and especially American, psychiatry from the end of World War II up to the present by interrogating a representative selection of psychiatrists and psychologists about the subject. Over a three-year period, the author surveyed approximately 200 mental health experts on their perceptions of change in the world of psychiatric theory and practice during this enormously eventful 70-year period. After presenting the survey results, the article then attempts to analyse the answers that the author did (and did not) obtain from his poll-taking subjects.

Asunto(s)

Psiquiatría/tendencias , Desinstitucionalización/tendencias , Historia del Siglo XX , Historia del Siglo XXI , Homosexualidad/psicología , Humanos , Psiquiatría/historia , Psicoanálisis/tendencias , Psicotrópicos/uso terapéutico

RESUMEN

22q11.2 microdeletion syndrome (22q11.2DS) is the most common syndrome associated with cleft palate and velopharyngeal insufficiency (VPI). Over 180 clinical features have been described. Most common features include: cardiac malformations, cleft palate, velopharyngeal insufficiency, characteristic facial features, hypotonia, behavioral disorders, and musculoskeletal disorders among several other fenotipical features. A case of 22q11.2DS confirmed by cytogenomic analysis is presented with review of the literature. Main clinical features were a submucous cleft palate (SMCP) with persistent VPI after palatoplasty, an ectopic left internal carotid artery and a prominent aortic root. VPI was corrected with a pharyngeal flap, tailored according to findings of videonasopharyngoscopy, videofluoroscopy and neck CT scan with contrast.

Asunto(s)

Fisura del Paladar/complicaciones , Síndrome de DiGeorge/diagnóstico , Endoscopía/métodos , Insuficiencia Velofaríngea/complicaciones , Niño , Fisura del Paladar/cirugía , Síndrome de DiGeorge/complicaciones , Síndrome de DiGeorge/cirugía , Femenino , Fluoroscopía , Humanos , Faringe/cirugía , Tomografía Computarizada por Rayos X , Insuficiencia Velofaríngea/cirugía

RESUMEN

Macrocerebellum is a rare condition characterized by enlargement of the cerebellum with conservation of the overall shape and cytoarchitecture. Here, we report on a child with a distinctive constellation of clinical features including macrocerebellum, epilepsy, apparent intellectual disability, dysautonomia, gut malrotation, and poor gut motility. Oligonucleotide chromosome microarray analysis identified a 16q24.1-q24.2 deletion that included four OMIM genes (FBXO31, MAP1LC3B, JPH3, and SLC7A5). Review of prior studies describing individuals with similar or overlapping16q24.1-q24.2 deletions identified no other reports of macrocerebellum. These observations highlight a potential genetic cause of this rare disorder and raise the possibility that one or more gene(s) in the 16q24.1-q24.2 interval regulate cerebellar development.

Asunto(s)

Anomalías Múltiples/genética , Cerebelo/anomalías , Deleción Cromosómica , Cromosomas Humanos Par 16 , Epilepsia/genética , Discapacidad Intelectual/genética , Anomalías Múltiples/diagnóstico , Cerebelo/patología , Preescolar , Mapeo Cromosómico , Femenino , Estudios de Asociación Genética , Humanos , Hibridación Fluorescente in Situ , Discapacidad Intelectual/diagnóstico , Imagen por Resonancia Magnética , Fenotipo

RESUMEN

BACKGROUND: During induction treatment, acute myeloid leukemia patients may develop pulmonary infiltrates due to infectious or noninfectious etiologies. The risk association and the clinical outcome of such pulmonary infiltrates are poorly characterized in the literature. METHODS: We retrospectively reviewed 363 cases of acute myeloid leukemia patients who received induction therapy as inpatients over a period of 11 years at William Beaumont Health System. Of these 363 patients, 120 developed pulmonary infiltrates during induction therapy, those patients were divided into 2 groups based on distribution of the infiltrate presenting as localized or diffuse in nature. Data on patients characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count at diagnosis, neutrophil count at the time the infiltrate was reported, response to antibiotic and/or antifungal therapy, using respiratory support, and mortality rate were retrieved through chart review. RESULTS: Thirty-three percent of patients developed pulmonary infiltrates during their induction therapy. Sixty-three patients (52.5%) had a localized infiltrates and 57 patients (47.5%) had diffuse infiltrates. Of the 120 patients with pulmonary infiltrates, 48 (40%) had at least 1 pathogenic microorganism identified, and 58 (48.7%) required intubation and ventilatory support. Patients with localized pulmonary infiltrates were more likely to have positive pathogenic microorganisms (68.3% vs. 8.8%, P<0.001), to be neutropenic (96.8% vs. 21%, P<0.001), and tended to have potentially reversible infiltrates after treatment (87.3% vs. 21%, P<0.001). Whereas patients with diffuse infiltrates were more like to require intubation (78.9% vs. 21%, P<0.001), to have leukocytosis (white blood cell >100 billions/L) at diagnosis (54.4% vs. 0%, P<0.001), and had a higher mortality rate (70.2% vs. 9.5%, P<0.001). CONCLUSIONS: The radiologic patterns of pulmonary infiltrates showed specific etiological and prognostic associations. Diffuse infiltrates are an unfavorable characteristic with overall dismal outcome.

Asunto(s)

Quimioterapia de Inducción/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Enfermedades Pulmonares/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Intubación , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Respiración Artificial , Estudios Retrospectivos , Tirosina Quinasa 3 Similar a fms/genética

RESUMEN

OBJECTIVES: Deep neck abscesses are complex head & neck problems that can lead to significant complications including life threatening infections. It is understood that the pathology of these infections is primarily polymicrobial. Although broad spectrum antibiotics can be effective for small abscesses, larger abscesses can be recalcitrant and difficult to treat with antibiotics. It has been demonstrated for several infectious diseases, including some of head & neck, that biofilm phenotypes present a unique model for recurrence and chronicity of infectious diseases. It is suspected that biofilm phenotypes could play a crucial role in the recalcitrance of large deep neck abscesses. This study presents initial evidence indicating the presence of polymicrobial biofilms in deep neck space infections. METHODS: Fourteen samples obtained via biopsy of abscess walls from deep neck spaces of patients undergoing surgical drainage. Eight patients were male and 6 were female. All but one patient were pediatric with ages ranging from 18 months to 32 years. All samples were processed and analyzed with scanning electron microscopy. RESULTS: Electron micrographs of 12 out of 14 specimens showed discrete biofilm architecture with individual bacteria, both rods and cocci, embedded within the matrix. This was starkly different from tissue surfaces devoid of biofilms. CONCLUSIONS: This initial evidence suggests that biofilm phenotypes could play a role in the pathogenesis and recalcitrance of deep neck infections, particularly in larger abscesses.

Asunto(s)

Fenómenos Fisiológicos Bacterianos , Biopelículas/crecimiento & desarrollo , Absceso Retrofaríngeo/microbiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Microscopía Electrónica de Rastreo , Cuello/microbiología , Cuello/cirugía , Adulto Joven

RESUMEN

Jacobsen syndrome is an uncommon but well-known contiguous gene syndrome caused by partial deletion involving the long arm of chromosome 11. Most common features include: psychomotor impairment, facial dysmorphism, and thrombocytopenia. Cleft palate has been rarely reported. A case of Jacobsen syndrome confirmed by cytogenomic analysis is presented with review of the literature. Main clinical features were phonological disorder, submucous cleft palate (SMCP) and velopharyngeal insufficiency (VPI). VPI was corrected surgically according to findings of videonasopharyngoscopy and videofluoroscopy. It is concluded that clinicians should consider that VPI associated with SMCP may be the main manifestations of a chromosomal syndrome.

Asunto(s)

Trastornos de la Articulación/diagnóstico , Fisura del Paladar/diagnóstico , Síndrome de Deleción Distal 11q de Jacobsen/diagnóstico , Insuficiencia Velofaríngea/diagnóstico , Trastornos de la Articulación/terapia , Niño , Cinerradiografía/métodos , Fisura del Paladar/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Síndrome de Deleción Distal 11q de Jacobsen/terapia , Laringoscopía/métodos , Enfermedades Raras , Insuficiencia Velofaríngea/diagnóstico por imagen , Insuficiencia Velofaríngea/cirugía

Asunto(s)

Neoplasias Orofaríngeas/patología , Sarcoma/patología , Biopsia con Aguja , Niño , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/cirugía , Pronóstico , Enfermedades Raras , Medición de Riesgo , Sarcoma/diagnóstico , Sarcoma/cirugía , Tomografía Computarizada por Rayos X/métodos

RESUMEN

Acute myelogenous leukemia (AML) secondary to acute lymphoblastic leukemia (ALL) in children is uncommon and usually occurs within 10 years of completing therapy for ALL. A variety of recurrent cytogenetic abnormalities have been described, suggesting significant biological heterogeneity. We report a case of highly refractory secondary AML with trisomy 10 and del(9q) occurring in an adolescent female 12 years after she was treated successfully for precursor B-cell ALL with chemotherapy only.

Asunto(s)

Cromosomas Humanos Par 10 , Cromosomas Humanos Par 9 , Leucemia Bifenotípica Aguda/genética , Leucemia Mieloide Aguda/genética , Trisomía , Adolescente , Preescolar , Aberraciones Cromosómicas , Bandeo Cromosómico , Deleción Cromosómica , Citogenética , Diploidia , Resultado Fatal , Femenino , Humanos , Cariotipificación , Leucemia Bifenotípica Aguda/patología , Leucemia Mieloide Aguda/complicaciones , Metafase

Asunto(s)

Linfocitos B/patología , Transdiferenciación Celular , Neoplasias Hipofaríngeas/etiología , Sarcoma de Células de Langerhans/etiología , Leucemia de Células Pilosas/patología , Seno Piriforme/patología , Anciano , Antígenos CD/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Docetaxel , Femenino , Reordenamiento Génico de Linfocito B , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patología , Inmunofenotipificación , Cariotipificación , Sarcoma de Células de Langerhans/tratamiento farmacológico , Sarcoma de Células de Langerhans/genética , Sarcoma de Células de Langerhans/patología , Leucemia de Células Pilosas/genética , Mutación , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Taxoides/administración & dosificación , Gemcitabina

RESUMEN

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

Asunto(s)

Proteínas Asociadas a Microtúbulos/genética , Mutación , Proteínas Nucleares/genética , Aneuploidia , Trastornos de los Cromosomas/genética , Humanos , Mosaicismo , Neoplasias/genética

RESUMEN

The simultaneous diagnosis of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare. This study reports a patient with composite synchronous biclonal occurrence of MALT lymphoma of the lung and CLL/SLL. The morphology of the lung and peripheral blood showed features of MALT lymphoma and CLL, respectively. The cytogenetic evaluation of the lung specimen revealed a t(1;14) (p22;q32), a frequent genetic abnormality in MALT lymphoma. Flow cytometry analysis of the lung tissue showed features of MALT lymphoma and CLL/SLL with different light chain restriction, whereas the blood showed phenotypic evidence of CLL/SLL. Fluorescence in situ hybridization study of the blood showed a deletion of 13q14 and 17p13. Immunoglobulin heavy chain (IgH) gene rearrangement study of the lung tissue and blood showed a monoclonal IgH gene rearrangement with distinct light chain restriction, suggesting that the immunophenotypically different cell populations originated from separate clones.

Asunto(s)

Leucemia Linfoide/patología , Neoplasias Pulmonares/patología , Linfoma de Células B de la Zona Marginal/patología , Citometría de Flujo , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia Linfoide/genética , Leucemia Linfoide/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/metabolismo , Masculino , Persona de Mediana Edad , Translocación Genética

Asunto(s)

Aborto Espontáneo/genética , Estudios Multicéntricos como Asunto , Trisomía , Femenino , Edad Gestacional , Humanos , Cariotipificación , Edad Materna , Embarazo , Primer Trimestre del Embarazo

RESUMEN

Primary bone diffuse large B-cell lymphomas (PB-DLBCL) are uncommon extranodal lymphomas. Herein, we report the clinical, pathologic, immunohistochemical, and molecular features of 21 cases of PB-DLBCL. The mean age of the patients was 54 years (range: 13 to 85 y). The male and female ratio was 1.6:1. The tumors consisted of diffuse sheets of large atypical cells or a polymorphous mixture of small-to-large cells with large multilobated nuclei, fine chromatin, and inconspicuous to prominent nucleoli. Twelve (57%) cases were non-germinal center B (GCB) and 9 (43%) were GCB subtype based on immunohistochemical classification. B-cell lymphomas (BCL)-2 was positive in 17/21 (81%), TP53 in 11/21 (52%) positive and the mean MIB-1 index was 57%. Polymerase chain reaction showed 10 cases with immunoglobulin heavy-chain (IGH) and 4 cases with IGH/BCL-2 gene rearrangement. The fluorescence in-situ hybridization analyses showed 14% of cases with BCL-6, 19% of cases with BCL-2, and 9% of cases with C-MYC gene rearrangement. Age <60 years and complete response to initial treatment were significant predictors of survival outcome (P< or =0.05). Even though no association was observed between the subtype of PB-DLBCL (GCB vs. non-GCB), BCL2, TP53, MIB1 index and overall survival (P>0.05), due to small sample size, and variability in treatment received, this analysis may be interpreted with caution.

Asunto(s)

Biomarcadores de Tumor/análisis , Neoplasias Óseas/patología , Linfoma de Células B Grandes Difuso/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Proteínas de Unión al ADN/genética , Femenino , Genes bcl-2 , Genes myc , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Antígeno Ki-67/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6 , Translocación Genética , Proteína p53 Supresora de Tumor/genética , Adulto Joven

RESUMEN

BACKGROUND: Malignant blue nevi arise within cellular blue nevi and contain atypical mitoses, necrosis, nuclear pleomorphism and prominent nucleoli. Malignant blue nevus has been described as a distinct identity, a rare form of malignant melanoma, and a misdiagnosed melanoma. METHODS: We present a patient with metastatic malignant blue nevus and studies on the histopathologic, immunohistochemical, and molecular features of the neoplasm. RESULTS: Histology showed a malignant blue nevus arising in a combined intradermal and cellular blue nevus. CD117 (c-kit) staining showed diffuse cytoplasmic expression within the cellular blue nevus, decreased staining in the malignant component, and variable positivity within the lymph node metastases. Molecular loss of heterozygosity analysis showed different allelic patterns at the hOGG-1 locus between the melanoma and control skin specimens with a varying heterozygous allelic pattern in both the benign and malignant blue nevus. CONCLUSIONS: Our case of malignant blue nevus with lymph node metastasis involved mutation of the hOGG-1 DNA repair gene. CD117 showed decreased staining of the primary malignant blue nevus with marked upregulation in the metastatic lesion, unlike most metastatic melanomas. Further study is needed to determine if hOGG-1 mutation or c-kit upregulation play a role in the pathogenesis of dendritic melanocytic lesions (either benign or malignant).

Asunto(s)

ADN Glicosilasas/genética , Antígeno Ki-67/metabolismo , Pérdida de Heterocigocidad , Nevo Azul , Proteínas Proto-Oncogénicas c-kit/metabolismo , Neoplasias Cutáneas , Anciano , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/genética , Nevo Azul/genética , Nevo Azul/metabolismo , Nevo Azul/patología , Nevo Azul/secundario , Reacción en Cadena de la Polimerasa , Cuero Cabelludo/patología , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Regulación hacia Arriba

RESUMEN

Mosaic variegated aneuploidy (MVA) is a rare condition characterized by multiple trisomies, rarely monosomies, and a non-specific phenotype including microcephaly, growth and mental retardation, mild malformations, and an increased risk of malignancy. We describe a patient with MVA in whom trisomy 19 mosaicism was originally suspected. The patient was the product of an uncomplicated term pregnancy and delivery. Significant findings were mental retardation, obesity, mild epicanthal folds, tapering fingers, relatively small hands and feet, alternating exotropia, nasal speech limited to short phrases, and generalized hypotonia. There is no family history for birth defects, mental retardation, or consanguinity. The initial peripheral blood chromosome study showed trisomy 19 in 4 of 31 metaphase cells. Because mosaic trisomy 19 is rare, the study was extended to 100 cells, wherein two cells with trisomy 8 were identified. A second blood karyotype was obtained and found to be 47,XX,+8[3]/47,XX,+19[3]/47,XX, +18[2]/47,XX,+9[1]/46,XX[91]. Skin fibroblast chromosome studies revealed a 46,XX karyotype in 120 cells examined. There was no evidence of premature centromere separation. Mutations in the BUB1B gene that encodes a key mitotic spindle checkpoint protein have been described in MVA; however, no mutations of this gene were identified in our patient. This case illustrates the importance of considering other possibilities when confronted with an extremely rare diagnosis such as mosaic trisomy 19. In addition, it shows the importance of not simply interpreting a low percentage of multiple aneuploidies as cell culture artifact, because an additional work-up to rule out MVA may be warranted since this diagnosis is associated with an increased risk of malignancy.

Asunto(s)

Anomalías Múltiples/diagnóstico , Aneuploidia , Mosaicismo , Trisomía/diagnóstico , Anomalías Múltiples/genética , Preescolar , Cromosomas Humanos Par 19 , Análisis Citogenético , Femenino , Humanos , Cariotipificación , Microcefalia/diagnóstico