Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association

European Journal of Pediatrics (Impact Factor: 1.98). 01/2009; 168(2):225-227. DOI: 10.1007/s00431-008-0732-z

ABSTRACT We report a 7-year-old girl with 22q13 deletion syndrome, 46,XX,Ish del(22)(q13.3)(ARSA-; D22S1726), who developed a fulminant
autoimmune hepatitis requiring orthotopic liver transplantation. Recently, it has been suggested that the Shank3 gene product,
whose deficiency is responsible for the features observed in this syndrome, could play a role in immunological response. Despite
an increased incidence of respiratory infections, autoimmune diseases have thus far not been reported in patients with this
syndrome. This is the first case of fulminant autoimmune hepatitis associated with the 22q13 deletion syndrome. The possible
relationships between immune system dysfunctions peculiar of this syndrome and autoimmune hepatitis are discussed.

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    ABSTRACT: We report a 5-year-old boy with mental retardation, autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2→qter. This region contains the SHANK3, NCAPH2 and CYP2D6 genes which are associated with T-cell immune response. The present case provides evidence that 22q13 deletion syndrome may be associated with immune system dysfunction in addition to neuropsychiatric disorders.
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    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.
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