Síndrome de Wolf-Hirschhorn (4p-). Diagnóstico prenatal de un caso asociado a oligoamnios y cardiopatía / Wolf-Hirschhorn syndrome (4p-). Prenatal detection of a case with oigoamnios and congenital heart defects

El síndrome de Wolf-Hirschhorn (SWH) está producido poruna deleción a nivel del brazo corto del cromosoma 4 (4p–). Existe una amplia variación en el tamaño de la deleción, correlacionándose el defecto citogenético con el fenotipo. La búsqueda de unos criterios ecográficos mínimos permitirán la orientación diagnóstica de este síndrome en el estudio prenatal. Presentamos un caso de una paciente que al realizar la ecografía selectiva en la semana 21 de gestación muestra oligoamnios y cardiopatía congénita. El estudio citogenético yla hibridación in situ fluorescente (HISF) (fluorescent in situ hybridization [FISH]) reveló la presencia de una deleción del brazo corto de cromosoma 4: 46,XX,del(4)(p14). Los padres optaron por interrumpir el embarazo y se realizó estudio necrósico al feto que mostró signos dismórficos craneofaciales típicos de SWH, así como malformaciones cardíacas. El diagnóstico prenatal del SWH se realiza habitualmente en fetos en los que se realiza cariotipo por indicaciones de rutinapara análisis cromosómico o por retraso de crecimiento intrauterino con o sin otras anomalías asociadas. Nosotros relacionamos nuestros hallazgos ecográficos: defectos de la línea media (defectos cardíacos septales) y oligoamnios como signos orientativos para el diagnóstico prenatal del SWH

Wolf-Hirschhorn syndrome (WHS) is a well-knowchromosomal disorder attributable to partial deletion ofthe short arm of chromosome 4 (4p–). We found ample variations in both the size of the deletions and the position of the respective breakpoints. Search of minimun ecographic criteria will make possible a diagnostic guide of such syndrome in prenatal studies. We report a case in which oligoamnios and congenital heart defects were detected by prenatal ultrasound examination at 21 weeks of gestation. Cytogenetic and FISH analysis of the cultured amniocytes revealed a 46,XX,del(4p14) karyotype. The parents opted to terminate the pregnancy. Fetopathological examinationshowed typical craneofacial dysmorphic signs of WHS andsevere congenital heart defects. Prenatal diagnosis of WHS has only been occasionally reported in fetuses karyotyped because of routine indications of chromosomal analysis or intrauterine growth restriction with or without associated anomalies. The associated sonographic signs of midline fusion defects (cardiac septal defects) and oligoamnios, may help to refine specific cytogenetic analysis taking into consideration 4p– syndrome

Diagnóstico prenatal y caracterización por SKY (cariotipo espectral multicolor) de cromosomas extra estructuralmente anormales (ESAC) / Prenatal diagnosis and multicolor spectral kariotyping characterization of the extra structurally abnormal chromosomes

Los cromosomas extra estructuralmente anormales (ESAC) son pequeños cromosomas supernumerarios asociados con cierta frecuencia con el desarrollo de anormalidades. Hemos revisado 9.987 estudios citogenéticos prenatales de células de líquido amniótico, encontrando tres casos con presencia de ESAC. Cada uno de estos cromosomas fueron analizados con varias técnicas con el fin de determinar su estructura, y con las técnicas citogenéticas moleculares como el FISH (hibridización in situ por fluorescencia) y SKY (cariotipo espectral multicolor). En dos casos pudimos determinar la presencia de ESAC en otros miembros normales de la familia. Un tercer caso de ESAC de novo fue detectado, y el origen cromosómico pudo ser determinado por SKY: 47,xx,+der(22) (q12-qter). La introducción de las técnicas de citogenética molecular como el SKY tiene un importante impacto en el correcto diagnóstico y en el consejo genético de acuerdo con la necesidad del paciente

Extra structurally abnormal chromosomes (ESACs) are small supernumerary chromosomes often associated with developmental abnormalities. We have revised 9,987 prenatal cytogenetic studies of amniotic fluid cells finding 3 cases with the presence of ESACs. Each of these chromosomes was analyzed with various staining techniques in orden to determine its structure, and with molecular cytogenetics techniques such FISH (fluorescence in situ hibridization) and SKY (multicolor spectral kariotyping). In two cases we could determine the presence of ESACs in other normal members of the families. In the third case a de novo ESAC was detected, and the chromosomal origin could be identified by SKY: 47,XX,+der(22)(q12-qter). The introduction of molecular cytogenetics techniques such SKY has a great impact on the correct diagnosis and we offered the genetic counseling according with the need of the patients

De novo trisomy 16p.

We report on a patient with psychomotor retardation and a pattern of malformations comprising single umbilical artery, craniofacial anomalies, severe truncal hypotonia, and lower-limb hyporreflexia. G-banding cytogenetics demonstrated a 16p+ chromosome. Parental chromosomes were normal. The use of fluorescent in situ hybridization (FISH) showed that this extra material derived from chromosome 16. High-resolution G-banding demonstrated a duplicated segment on the 16p arm, confirming our suspicion of a de novo tandem duplication; hence, the cytogenetic diagnosis was given as 46,XY,dir dup(16)(p11.2-->p12).

Deletion of exon b3 of the BCR gene in CML: easy breakpoint mapping by a two-round PCR.

We have performed the molecular analysis for the detection of the BCR-ABL and ABL-BCR fusion genes in 50 patients with myeloproliferative disorders. All patients diagnosed with CML (13 out of 50) were positive for the BCR-ABL hybrid. Six CML patients (46%) showed ABL-BCR amplifications of the Ib-BCR type. All rearrangements but one were concordant. The aberrant case presented a deletion of exon b3, in addition to the alternative Ib-BCR and Ia-BCR. Its possible origin and relevance are briefly discussed.

BCR-ABL rearrangement and 'variant' Philadelphia chromosome in de novo acute myelogenous leukaemia FAB subtype M1.

We report a case of de novo acute myelogenous leukaemia FAB subtype M1 that presents a cytogenetic complex translocation between chromosomes 7, 9 and 22, producing a 'variant' Philadelphia chromosome. Molecular analysis revealed a BCR-ABL rearrangement involving exons b3 and a2 (b3a2). Haematological parameters and genetic analysis again raise the problem of the true nature of this disease, which is briefly discussed.

Translocation (5;19)(q13;q13) in a multinodular thyroid goiter.

We describe the cytogenetics of a multinodular thyroid goiter where 90% of the analyzed cells showed a diploid karyotype with a balanced translocation between chromosomes 5 and 19: 46,XX,t(5;19)(q13;q13). This translocation has been previously described in cases of thyroid adenoma. Our case is the first report of this anomaly in nodular hyperplasia. We discuss its putative role in the neoplastic transformation of thyroid lesions.

Deletion (7)(p11p15) in a patient with Philadelphia-positive chronic myelogenous leukemia.

We report a case of chronic myelogenous leukemia (CML) with a Philadelphia (Ph) chromosome. During the transformation phase of the disease, a del(7)(p11p15) and a +Ph were identified as additional chromosomal anomalies. We believe that loss of the segment 7p11-->p15 may play an important role in the progression of the disease.

AML with unusual chromosomal changes. Translocation (15;21) and 5q- in the presence of two normal chromosomes 5.

We performed serial cytogenetic studies of the bone marrow (BM) of a patient with acute myeloblastic leukemia (AML) and noted abnormal karyotypes 47,XY,+del(5)(q12q34),t(15;21)(q21;q22)/47,XY,+del(5)(q12q34 ) during the second relapse. Although a case of this t(15;21) was recently observed in a female patient with acute nonlymphocytic leukemia (ANLL) of subtype M4 of the French-American-British (FAB) classification, the present article constitutes the first report of its occurrence in association with ANLL of subtype M1-M2. Furthermore, the presence of the 5q- accompanied by two chromosomes 5 of normal appearance is very rare and of great interest.

Small marker chromosomes in a series of 1,000 prenatal diagnoses by amniocentesis.

We diagnosed two small marker chromosomes in a series of 1,000 prenatal cytogenetic studies of amniotic fluid cells. Each of these chromosomes was analyzed with various staining techniques in order to determine its structure and the possible mechanism of its formation. On the basis of the results thus obtained and the familial nature of these abnormalities, we predicted phenotypically normal fetuses in both cases. Postnatal follow-up confirmed this. Notwithstanding the correct diagnoses made in these two cases, we feel that a more substantial body of literature on this type of anomaly must become available before it will be possible to give firm genetic counselling in such cases.

A rare case of de novo structural rearrangement of X chromosome diagnosed by amniocentesis.

A dicentric X chromosome was found in a female fetus during cytogenetic studies performed on amniotic cells. Blood samples from the parents showed normal karyotypes and the pregnancy was terminated. The mechanism for the formation of this 'de novo' rearrangement is discussed.

Monosomy 22 with humoral immunodeficiency: is there an immunoglobulin chain deficit?

The cytogenetic analysis of a patient with selective deficit of IgA and decrease in IgM, IgE, and IgG is presented. Using trypsin-Giemsa banding the karyotype showed monosomy 22 (45,XX,-22). The interest of this case lies in the rarity of the illness and in the association of monosomy 22 with hypogammaglobulinaemia and selective deficit of IgA, particularly as this chromosome is known to contain genes coding for immunoglobulin chains.

[Holt-Oram syndrome with chromosomopathy (author's transl)]. / Síndrome de Holt-Oram con cromosomopatía.

A patient whose cardiac and skeletal malformations are compatible with Holt-Oram syndrome is presented. The interest lays in the fact that cytogenetic shows and excess of chromosomic material in the long arm of the sixth chromosome. Authors consider this to be a "de novo" finding as the study practiced on the parents has been normal. This chromosomic anomaly has not been, to their knowledge, reported in the literature. All known cases have a normal karyotype.