Application of chromosome microarray analysis in neonatal birth defects / 中华实用儿科临床杂志

Objective@#To explore the application of chromosomal microarray analysis (CMA) in neonatal birth defects and further determine the frequency of chromosome imbalances in neonates with birth defects.@*Methods@#Retrospective analysis was performed in 121 neonates with specific features, such as distinctive facial features, congenital heart disease, congenital malformation, neonatal decreased responsive, hypotonia, seizures and others at the Department of Neonatology, Guangdong Women and Children Hospital from May 2016 to November 2017.All the cases were analyzed by using chromosomal microarray analysis (CMA).@*Results@#A total of 23 (19.0%) patients were identified with pathogenic CNVs, 3 patients (2.5%) with uncertain clinical significant CNVs.There were 5 patients (4.1%)with chromosome numerical abnormalities, 12 patients (9.9%)with microdeletion/microduplication syndrome, 6 patients (5.0%) with chromosome deletion or duplication.All groups whose incidence was sorted from high to low were facial characters(30.3%), congenital malformation(21.6%), neonatal decreased responsive(9.1%) and other indications(6.7%).@*Conclusions@#CMA is a valuable clinical diagnostic tool that allows precise identification of chromosome imbalances as the cause of birth defects in neonates.CMA can detect many more clinically relevant genomic abnormalities than conventional cytogenetic study and assist the clinician in diagnosis, early neonatal intervention, and genetic counseling.

Recién nacida normal con sospecha prenatal de monosomía del cromosoma X debido a mosaicismo confinado a la placenta / Normal newborn with prenatal suspicion of X chromosome monosomy due to confined placental mosaicism

La reciente introducción de las pruebas prenatales no invasivas (NIPT, por sus siglas en inglés) basadas en el ADN libre ofrece un método más preciso que los métodos tradicionales de detección en el suero materno para identificar aneuploidías fetales. La eficacia de las pruebas NIPT para detectar los síndromes de Down, Edwards y Patau se ha demostrado en ensayos clínicos. Sin embargo, los enfoques de las pruebas NIPT que aprovechan la información sobre el polimorfismo de un solo nucleótido (SNP, por sus siglas en inglés) tienen el potencial de identificar triploidías, síndromes de microdeleción cromosómica y otras variantes genéticas no habituales. Para destacar este enfoque de las pruebas NIPT, se presenta un caso poco frecuente de monosomía del cromosoma X debido a mosaicismo confinado a la placenta, del que había una sospecha prenatal por el resultado de una prueba prenatal no invasiva basada en el polimorfismo de un solo nucleótido. Los resultados de las pruebas invasivas (amniocentesis) mostraron una pequeña proporción de mosaicismo del cromosoma X (45, X[5]/46, XX[95]). Después del nacimiento, el cariotipo de la niña no reveló anomalías (46 XX), lo que confirmó que el mosaicismo se limitaba a la placenta. Estos resultados ponen de manifiesto la necesidad del consentimiento informado de la paciente, y del minucioso asesoramiento anterior y posterior a las pruebas, para garantizar que comprenda las limitaciones y las ventajas de dichas pruebas, y las repercusiones de los resultados.

The recent introduction of cell-free DNA (cfDNA)-based noninvasive prenatal testing (NIPT) offers pregnant women a more accurate method than traditional serum screening methods for detecting fetal aneuploidies. Clinical trials have demonstrated the efficacy of NIPT for Down, Edwards and Patau syndromes. However NIPT approaches that take advantage of single-nucelotide polymorphism (SNP) information potentially allow the identification of triploidy, chromosomal microdeletion syndromes and other unusual genetic variants. To highlight this approach of NIPT we present a rare case of confined placental X chromosome monosomy mosaicism that was prenatally suspected with a single-nucleotide polymorphism-based noninvasive prenatal test. The results of invasive tests (amniocentesis) showed small proportion of X chromosome mosaicism (45, X[5]/46, XX[95]). After birth karyotype of the girl revealed no abnormalities (46 XX), confirming that mosaicism was limited to the placenta. These results highlight the need of patient's informed consent and thorough pretest and postest counseling to ensure that they understand the limitations and advantages of the tests and the implications of the resultss.

A Case of 17q22 with Interstitial Deletion

Cases of interstitial deletions of the long arm of chromosome 17 are very rare, with only nine cases ever reported worldwide. We describe a 12-year-old boy with profound developmental delay, microcephaly, facial dysmorphism, contracture of the large joints and bilateral hearing loss. A chromosomal study using a peripheral blood sampled revealed 46,XY,del(17)(q22q23). To our knowledge, he is the first case of interstitial deletion of the long arm of chromosome 17 ever reported in Korea.

A Case of Del 13(q24) Syndrome with Multiple Anomalies / 소아과

It has been estimated that chromosomal aberrations account for 2.3% to 3% of normal pregnancies, and of them, 85% are aborted. Therefore, the survival rate of neonates with chromosomal aberrations is very low. Among them, patients with partial deletion of the long arm of chromosome 13 are very rare. The natural history of deletion of the long arm is dependent on the deleted segment. It has been known that patients with proximal deletions not extending into q32 usually show mild to moderate mental retardation, variable minor anomalies, and growth retardation. Patients with more distal deletions, including at least part of q32, usually have severe mental retardation, growth deficiency, and major malformations including microcephaly and CNS defects, distal limb anomalies, eye defects, and gastrointestinal malformation. We report a case of a 13(q24) deletion male infant who showed intrauterine growth retardation, imperforate anus, CNS anomalies, hydronephrosis, clubfoot, clinodactyly and developmental delay, although his deletion site was proximal to q32.