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 ∼55 genes; from NUP50 to RABL2B ) and in the previous patient a 1.535 Mb deletion (22q13.32 → qter; including ∼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. © 2010 Wiley‐Liss, Inc.