RESUMO
OBJECTIVE: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield. METHODS: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes. RESULTS: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days. CONCLUSION: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.
Assuntos
Anormalidades Múltiplas/diagnóstico , Sequenciamento do Exoma , Diagnóstico Pré-Natal/métodos , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Adulto , Testes Diagnósticos de Rotina/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Feto/diagnóstico por imagem , Testes Genéticos/métodos , Testes Genéticos/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Países Baixos/epidemiologia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez/epidemiologia , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Prospectivos , Ultrassonografia Pré-NatalRESUMO
Intracranial lipomas are rare congenital malformations. The most common type of intracranial lipoma is the interhemispheric lipoma, which is frequently associated with callosal anomalies such as hypogenesis or agenesis of the corpus callosum. In contrast, interhemispheric lipomas are less often accompanied with malformations of cortical development (MCD). We report magnetic resonance imaging findings of three infants with an interhemispheric lipoma, associated with a callosal anomaly, and MCD: two infants with nodular interhemispheric lipoma, agenesis of the corpus callosum, and polymicrogyria, and one infant with interhemispheric curvilinear lipoma, hypoplasia of the corpus callosum, and heterotopias. An association was suggested regarding the occurrence of these malformations.