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Eur J Pediatr (2011) 170:14751480 DOI 10.1007/s00431-011-1539-x
SHORT REPORT
A novel SOX10 mutation in a patient with PCWH who developed hypoxicischemic encephalopathy after E. coli sepsis
Alexandra Unzicker & Veronique Pingault &
Thomas Meyer & Stephan Rauthe & Ansgar Schtz &
Steffen Kunzmann
Received: 29 April 2011 /Accepted: 18 July 2011 /Published online: 6 August 2011 # Springer-Verlag 2011
Abstract We describe a male infant with a novel SOX10 mutation and a severe course of PCWHa special phenotype of Shah-Waardenburg syndrome involving peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprungs disease. The patient had severe hypoplastic hypoganglionosis of the small and total colonic intestine together with peripheral and central dysmyelination. The patient was completely dependent on parenteral nutrition. We identified a novel frameshift mutation,p.Asp293GlyfsX10, in the SOX10 gene of this patient. The mutation would encode a protein that lacked the trans-activation domain and resulted in the largest duplication described to date. At the age of 20 months, the boy presented with a severe complication with a translocation of Escherichia coli and developed sepsis leading to severe hypoxicischemic
encephalopathy with persistent vegetative state (PVS). The boy died at the age of 24 months. Conclusion: Septic encephalopathy with hypoxicischemic encephalopathy can be a serious complication in severe sepsis. It is unknown to what extent the mutant SOX10 protein influenced the degree of brain injuryfor example central nervous system susceptibility to hypoxiaduring sepsis, which may explain the severe encephalopathy with clinical signs of PVS the boy developed.
Keywords Shah-Waardenburg syndrome . SOX10 . Hypoxicischemic encephalopathy. Hirschsprungs disease . E. coli sepsis
AbbreviationsWS Waardenburg syndromePCWH Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, Hirschsprungs diseaseEDN3 Endothelin-3EDNRB Endothelin-B receptorPVS Persistent vegetative stateSOX10 Sex-determining region Y box-10MITF Microphthalmia-associated transcription factor PAX Paired box
Introduction
Waardenburg syndrome (WS) (MIM 193500), first described in 1951 by the Dutch ophthalmologist and geneticist PJ Waardenburg, is a rare (1:40,000) genetic disorder characterized by auditory and pigmentary features [17]. The main characteristics are pigmentary disturbances of the iris, hair, and skin, which are a result of abnormal melanocyte development, and sensorineural hearing loss
A. Unzicker : S. Kunzmann (*)
Childrens Hospital, University of Wrzburg, Josef-Schneider-Strasse 2,97080 Wrzburg, Germanye-mail: [email protected]
T. MeyerPediatric Surgery Unit, University of Wrzburg, Wrzburg, Germany
S. RautheInstitute of Pathology, University of...