Carey-Fineman-Ziter Syndrome: A MYMK-Related Myopathy Mimicking Brainstem Dysgenesis.

Carey-Fineman-Ziter syndrome is a congenital myopathy associated with mutations in the MYMK gene. It is clinically defined by the combination of hypotonia, Moebius-Robin sequence, facial anomalies and motor delay. Historically it was considered a brainstem dysgenesis syndrome. We provide detailed information of a Spanish boy with compound heterozygous variants in MYMK gene. A muscle biopsy performed as a toddler only disclosed minimal changes, but muscle MRI showed severe fatty infiltration of gluteus muscles and to a lesser extent in adductors magnus, sartorius and soleus muscles. Clinical course is fairly static, but the identification of new well characterized genetic cases will help to delineate the complete phenotype.

Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-.

BACKGROUND: More than 50% of patients with myelodysplastic syndromes present cytogenetic aberrations at diagnosis. Partial or complete deletion of the long arm of chromosome 5 is the most frequent abnormality. The aim of this study was to apply fluorescence in situ hybridization of 5q31 in patients diagnosed with de novo myelodysplastic syndromes in whom conventional banding cytogenetics study had shown a normal karyotype, absence of metaphases or an abnormal karyotype without evidence of del(5q). DESIGN AND METHODS: We performed fluorescence in situ hybridization of 5q31 in 716 patients, divided into two groups: group A patients (n=637) in whom the 5q deletion had not been detected at diagnosis by conventional banding cytogenetics and group B patients (n=79), in whom cytogenetic analysis had revealed the 5q deletion (positive control group). RESULTS: In group A (n=637), the 5q deletion was detected by fluorescence in situ hybridization in 38 cases (5.96%). The majority of positive cases were diagnosed as having the 5q- syndrome. The deletion was mainly observed in cases in which the cytogenetics study had shown no metaphases or an aberrant karyotype with chromosome 5 involved. In group B (n=79), the 5q deletion had been observed by cytogenetics and was confirmed to be present in all cases by fluorescence in situ hybridization of 5q31. CONCLUSIONS: Fluorescence in situ hybridization of 5q31 detected the 5q deletion in 6% of cases without clear evidence of del(5q) by conventional banding cytogenetics. We suggest that fluorescence in situ hybridization of 5q31 should be performed in cases of a suspected '5q- syndrome' and/or if the cytogenetic study shows no metaphases or an aberrant karyotype with chromosome 5 involved (no 5q- chromosome).

Deletion of sequences flanking the t(9;22) breakpoint: a secondary genetic event associated with loss of cytogenetic response to interferon in a Philadelphia-positive chronic myeloid leukaemia patient.

We present a Ph-positive chronic myeloid leukaemia patient who lost a complete cytogenetic response (CCR) of 23 months duration at the time of detection of a deletion, not previously observed, of chromosomes 9 and 22 sequences flanking the translocation breakpoint on the derivate 9 chromosome. To our knowledge, this is the first case in which a deletion at the t(9;22) breakpoint has arisen as a secondary genetic alteration produced after formation of the t(9;22) translocation. It remains to be determined whether this genetic abnormality has the same prognostic importance as when observed at diagnosis.

Diagnóstico prenatal y array-hibridación genómica comparada (CGH) (I). Gestaciones de elevado riesgo / Prenatal diagnosis and comparative genomic hybridization (CGH) -array (I). High risk pregnancies

Objetivos. Revisar los principios de los microarrays (en concreto array-CGH [a-CGH]), sus beneficios para el diagnóstico prenatal y los desafíos asociados, a través de los trabajos actualmente publicados y aquellos derivados de nuestra experiencia práctica en los dos últimos años. Métodos. Revisión de la literatura y comparación con estudios prospectivos y retrospectivos con array-CGH en casos de gestaciones con elevado riesgo (preferentemente con alteraciones ecográficas). Resultados. La tasa de detección de alteraciones genómicas por a-CGH en nuestros casos con alteraciones ecográficas fue de entre el 13,3 y el 15%. Conclusión. La combinación de la mayor capacidad de los microarrays en el cribado del genoma humano para la detección de cambios en números de copias, dentro de un único ensayo experimental, así como su mayor resolución técnica en casos de gestaciones de elevado riesgo, podría convertir a los array-CGH, en la próxima década, en una alternativa muy interesante para reemplazar al cariotipo convencional como test diagnóstico de primera línea, en estos casos(AU)

Objectives. Review the principles of microarrays (in particular array-CGH), their benefits for prenatal diagnosis and the associated challenges, through the currently published works and those derived from our practical experience over the past two years. Methods. A literature review was carried out, as well as comparisons with prospective and retrospective studies with array-CGH in cases of pregnancies at high risk (preferably with ultrasound anomalies). Results. The detection rate of genomic alterations by array-CGH in our cases with ultrasound anomalies was between 13.3-15%. Conclusion. The combination of the increased capacity of microarrays in screening of the human genome to detect changes in copy numbers variations, within a single experimental assay, as well as their greater technical resolution in cases of high-risk pregnancies, could lead to array-CGH to be a very interesting diagnostic approach in the next decade to replace the karyotype as a gold standard in such prenatal studies(AU)