title: Fulminant hepatic failure requiring liver transplantation in 22q13.3 deletion syndrome.
abstract: 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.
authors.affiliation: Johannes Gutenberg-University Mainz, Institute of Human Genetics, Mainz, Germany. bartsch@humgen.klinik.uni-mainz.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Bartsch
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schneider
authors.forename: Natalja
authors.initials: N
authors.lastname: Damatova
authors.forename: Roger
authors.initials: R
authors.lastname: Weis
authors.forename: Maria
authors.initials: M
authors.lastname: Tufano
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
authors.forename: Alischo
authors.initials: A
authors.lastname: Ahmed
authors.forename: Vera
authors.initials: V
authors.lastname: Beyer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017114:Liver Failure, Acute / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016031:Liver Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D013577:Syndrome