Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome

We report on a 4-year-old girl with severe developmental delay, absent speech, and chromosome 22q13.3 deletion (Phelan-McDermid syndrome), karyotype 46,XX.ish del(22)(q13.31qter)(ARSA-,N85A-,SHANK3-). At the age of 3 years, she needed an emergency liver transplantation because of fulminant hepatic failure, most likely caused by hyperacute autoimmune hepatitis triggered by a viral infection. This is the second report of a patient with 22q13.3 deletion and fulminant liver failure. By array-CGH we identified in this patient a 5.675 Mb terminal deletion (22q13.31 --> qter; including approximately 55 genes; from NUP50 to RABL2B) and in the previous patient a 1.535 Mb deletion (22q13.32 --> qter; including approximately 39 genes; from BRD1 to RABL2B). PIM3 is a prime candidate gene for the fulminant hepatic failure in the two patients; SHANK3/PROSAP2 could be another candidate gene. We recommend liver function tests and array-CGH in the management of patients with Phelan-McDermid syndrome. This patient showed a developmental catch-up following the liver transplantation, possibly suggesting that chronic hepatic disease could contribute to the developmental delay in a subset of these patients.