TY  - JOUR
AU  - Hinreiner, Sophie
AU  - Melter, Michael
AU  - Segerer, Hugo
AU  - Herbst, Saskia
AU  - Brandl, Roland
AU  - Geis, Tobias
AU  - Hehr, Ute
PY  - 2018
DA  - 2018/03/06
TI  - Application of Clinical Next Generation Sequencing in Intensive Care Facilitates Rapid Diagnosis of Neonates with Rare Genetic Disorders
JO  - OBM Genetics
SP  - 015
VL  - 02
IS  - 01
AB  - Background: Neonatal muscular hypotonia is a common clinical feature on neonatal intensive care units with a broad spectrum of etiologies. Besides more common and obvious underlying conditions like prematurity or Down syndrome many rare disorders with often poor prognosis need to be considered. Congenital brain malformations detected on ultrasound or/and magnetic resonance imaging might constitute the clinical hallmark in differential diagnosis. We report on our approach combining cerebral imaging and application of targeted next generation panel sequencing.
Methods: Retrospective review and evaluation of patients´ files and cerebral images of 4 severely affected neonates treated at the neonatal intensive care unit of our university children’s hospital in 2016 with confirmed genetic diagnosis using clinically targeted multi gene panel sequencing and/or Sanger sequencing. 
Results: Detailed presentation of the phenotype and genotype of 4 neonates with muscular hypotonia and abnormal MR imaging due to genetically confirmed Aicardi-Goutières syndrome (TREX1), Zellweger spectrum disorder (PEX13), Pontocerebellar Hypoplasia (TSEN54) and X-linked Hydrocephalus (L1CAM), respectively. Overview of genetic and metabolic disorders with brain malformations presenting with neonatal onset muscular hypotonia as a leading symptom.
Conclusions: Comprehensive multidisciplinary clinical evaluation of patients with neonatal muscular hypotonia allows phenotype based individual genetic testing including novel  targeted multi gene panel testing. This approach might ultimately improve the turn-around time and diagnostic yield including a wide range of very rare genetic disorders.
SN  - 2577-5790
UR  - https://doi.org/10.21926/obm.genet.1801015
DO  - 10.21926/obm.genet.1801015
ID  - Hinreiner2018
ER  -