Change in prevalence of congenital defects in children with Prader-Willi syndrome.

OBJECTIVE: The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. METHODS: A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). RESULTS: Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. CONCLUSIONS: An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

New recurrent chromosome alterations in patients with multiple myeloma and plasma cell leukemia.

Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), ß(2) microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.

[Angelman syndrome: the electroclinical characteristics in 35 patients]. / Sindrome de Angelman: características electroclínicas en 35 pacientes.

AIMS: The purpose of this study is to report on 35 patients with Angelman syndrome (AS) in whom we evaluated the electroclinical characteristics and the progression of their epilepsy. PATIENTS AND METHODS: The following factors were evaluated: sex, family background, neurological examination, age at onset and semiology of the epileptic seizures, EEG, types of epilepsy according to the international classification and response to therapy. We investigated the karyotype, and conducted FISH and methylation tests for AS. RESULTS: The 35 patients had an average follow up time of 5.6 years. Epilepsy was diagnosed in 25 cases, with an average age of onset of 1.6 years. The epileptic syndromes were: epilepsy with myoclonic seizures in 13, of which seven presented a myoclonic state in their history, focal epilepsy in seven, West's syndrome in three, and Lennox Gastaut syndrome in two. Intercritical EEG showed generalised MSW and SW paroxysms in 13, unilateral spikes in seven, hypsarrhythmia in three, generalised fast rhythm paroxysms and slow SW activity in two. Basal electroencephalographic activity was: slow hypervoltage waves with or without inserted spikes situated at the rear in 19, at the front in six, diffuse in six, and normal in four cases. CONCLUSIONS: 71.4% of patients with AS suffered epileptic seizures; epilepsy with myoclonic seizures was the most frequently observed epileptic syndrome and hypervoltage slow wave activity with or without spikes inserted in the posterior quadrants was a characteristic encephalographic pattern. In patients with mental retardation, with or without epilepsy and these electroencephalographic findings, even in the absence of characteristic clinical signs, methylation and FISH analyses for AS should be performed.

Síndrome de Angelman: características electroclínicas en 35 pacientes / Angelman syndrome: the electroclinical characteristics in 35 patients

Objetivo. Presentar 35 pacientes con síndrome de Angelman (SA) en los que se evaluaron las características electroclínicas y el curso evolutivo de la epilepsia. Pacientes y métodos. Evaluamos: sexo, historia familiar, examen neurológico, edad de inicio y semiología de las crisis epilépticas, EEG, tipos de epilepsia de acuerdo a la clasificación internacional y respuesta al tratamiento. Investigamos cariotipo, FISH y test de metilación para SA. Resultados. Los 35 pacientes tuvieron un tiempo promedio de seguimiento de 5,6 años. La epilepsia se diagnosticó en 25 casos, con una mediana para la edad de inicio de 1,6 años. Los síndromes epilépticos fueron: epilepsia con crisis mioclónicas en 13, de los cuales siete presentaron estado miocló nico en su evolución, epilepsia focal en siete, síndrome de West en tres, síndrome de Lennox-Gastaut en dos. El EEG intercrítico mostró paroxismos generalizados de PPO y PO en 13, espigas unilaterales en siete, hipsarritmia en tres, paroxismos generalizados de ritmos rápidos y actividad de PO lenta en dos. La actividad electroencefalográfica basal fue: ondas lentas hipervoltadas con o sin espigas intercaladas de localización posterior en 19, anterior en seis, difusas en seis; y normal, cuatro casos. Conclusiones. El 71,4 por ciento de los pacientes con SA tuvieron crisis epilépticas; la epilepsia con crisis mioclónicas fue el síndrome epiléptico más frecuente y la actividad de OL hipervoltadas con o sin espigas intercaladas en cuadrantes posteriores fue patrón electroencefalográfico característico. En pacientes con retraso mental, con o sin epilepsia y estos hallazgos electroencefalográficos, aun en ausencia de signos clínicos característicos, deberíamos realizar test de metilación y FISH para SA (AU)

Aims. The purpose of this study is to report on 35 patients with Angelman syndrome (AS) in whom we evaluated the electroclinical characteristics and the progression of their epilepsy. Patients and methods. The following factors were evaluated: sex, family background, neurological examination, age at onset and semiology of the epileptic seizures, EEG, types of epilepsy according to the international classification and response to therapy. We investigated the karyotype, and conducted FISH and methylation tests for AS. Results. The 35 patients had an average follow-up time of 5.6 years. Epilepsy was diagnosed in 25 cases, with an average age of onset of 1.6 years. The epileptic syndromes were: epilepsy with myoclonic seizures in 13, of which seven presented a myoclonic state in their history, focal epilepsy in seven, West's syndrome in three, and Lennox-Gastaut syndrome in two. Intercritical EEG showed generalised MSW and SW paroxysms in 13, unilateral spikes in seven, hypsarrhythmia in three, generalised fast-rhythm paroxysms and slow SW activity in two. Basal electroencephalographic activity was: slow hypervoltage waves with or without inserted spikes situated at the rear in 19, at the front in six, diffuse in six, and normal in four cases. Conclusions. 71.4% of patients with AS suffered epileptic seizures; epilepsy with myoclonic seizures was the most frequently observed epileptic syndrome and hypervoltage slow wave activity with or without spikes inserted in the posterior quadrants was a characteristic encephalographic pattern. In patients with mental retardation, with or without epilepsy and these electroencephalographic findings, even in the absence of characteristic clinical signs, methylation and FISH analyses for AS should be performed (AU)

[Translocation t(9;11) in acute childhood lymphoblastic leukemia]. / Traslocación t (9;11) en leucemia linfoblástica aguda en pediatría.

We report a case of a de novo acute lymphoblastic leukaemia (ALL) with t(9;11) (p21;q23) and a novel translocation t(2;8) (p15;q24). The former is characteristic of acute nonlymphoblastic leukaemia (ANLL) and has rarely been detected in ALL. The blasts showed L2 morphology by the French American British (FAB) classification and pre B ALL immunophenotype.

Tandem triplication and quadruplication of chromosome 21 in childhood acute lymphoblastic leukemia.

A 5-year-old girl with ALL was shown to have a leukemic clone characterized by a triplication and quadruplication of chromosome 21, arranged in tandem, at diagnosis and relapse, respectively. To our knowledge, this is the second report of this chromosomal anomaly in ALL, which was confirmed by in situ staining. The karyotype evolution in the leukemic clone from triplication to quadruplication at relapse emphasizes the association of chromosome 21 with hematopoietic malignancies.

New variant Ph translocation in chronic myeloid leukemia: t(Y;22)(p11;q11).

A 4-year-old boy with chronic myeloid leukemia (CML) was shown to have a variant Ph t(Y;22)(p11;q11). To our knowledge, this is the first report of a variant Ph translocation involving Y. Molecular analysis showed that the breakpoint on chromosome 22 is in the breakpoint cluster region (bcr), typical of CML with the classic t(9;22), suggesting that it might be a complex Ph translocation with the involvement of 9q34.