A novel SOX10 mutation in a patient with PCWH who developed hypoxic-ischemic encephalopathy after E. coli sepsis

作者：Unzicker Alexandra; Pingault Veronique; Meyer Thomas; Rauthe Stephan; Schuetz Ansgar; Kunzmann Steffen^*

来源：European Journal of Pediatrics, 2011, 170(11): 1475-1480.

DOI：10.1007/s00431-011-1539-x

• Shah-Waardenburg syndrome
• SOX10
• Hypoxic-ischemic encephalopathy
• Hirschsprung's disease
• E. coli sepsis

We describe a male infant with a novel SOX10 mutation and a severe course of PCWH-a special phenotype of Shah-Waardenburg syndrome involving peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung's 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 transactivation 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 hypoxic-ischemic encephalopathy with persistent vegetative state (PVS). The boy died at the age of 24 months. Conclusion: Septic encephalopathy with hypoxic-ischemic encephalopathy can be a serious complication in severe sepsis. It is unknown to what extent the mutant SOX10 protein influenced the degree of brain injury-for example central nervous system susceptibility to hypoxia-during sepsis, which may explain the severe encephalopathy with clinical signs of PVS the boy developed.

• 出版日期2011-11