Details

Autor(en) / Beteiligte

• Kuehne, Benjamin
• Heine, Eva
• Dafsari, Hormos Salimi
• Irwin, Raphael
• Heller, Raoul
• Bangen, Ursula
• Brockmeier, Konrad
• Kribs, Angela
• Oberthuer, André
• Cirak, Sebahattin

Titel

Use of whole exome sequencing in the NICU: Case of an extremely low birth weight infant with syndromic features

Ist Teil von

• Molecular and cellular probes, 2019-06, Vol.45, p.89-93

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Single gene (Mendelian) disorders are one of the leading causes of neonatal morbidity and mortality. However, in the setting of preterm birth phenotypic features of genetic diseases are often undifferentiated and are clinically very difficult to interpret based on the wide range of differential diagnoses. We report an extremely low birth weight infant (ELBW) born prematurely at 23 + 0 gestational weeks after twin pregnancy with a novel clinical manifestation with persistent hyperglycaemia as well as the known manifestations of disease-associated hypokinesia, renal salt wasting, and multifocal atrial tachycardia. The patient died of heart failure on the 72nd day of life. Whole exome sequencing (WES) revealed a previously well established, disease-causing heterozygous likely pathogenic variant in the Harvey rat sarcoma viral oncogene homolog (HRAS)-gene (c.35G > C, p. G12A, rs104894230), which implied the clinical diagnosis of Costello syndrome (CS; OMIM#190020.0004). The twin brother merely had complications related to preterm birth and did not show any CS symptoms. In conclusion, our case illustrated that CS should be considered in ELBW infants showing a life-threatening combination of complex cardiac arrhythmia and hypokinesia. If a syndromic disorder is suspected in the neonatal intensive care unit (NICU) setting, rapid WES is a useful, non-invasive diagnostic tool in critically ill ELBW infants. •Clinical challenges of diagnosing an extremely low birth weight infant (ELBW) born prematurely   with Costello Syndrome (CS).•Whole Exome sequencing (WES) revealed heterozygote likely pathogenic variant in HRAS-gene (c.35G > C, p. G12A) causing CS.•The case illustrated that CS should be considered in neonates showing a combination of complex arrhythmia, hyperglycaemia and hypokinesia.•WES or ultra rapid WGS represents a useful and appropriate diagnostic tool for critically ill infants.