Johannes Gutenberg-University Mainz, Institute of Human Genetics, Mainz, Germany.
Am J Med Genet A. 2010 Aug;152A(8):2099-102. doi: 10.1002/ajmg.a.33542.
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.
我们报告了一例 4 岁女孩，患有严重的发育迟缓、无言语能力，染色体 22q13.3 缺失（即普莱汉姆-麦克德米德综合征），核型为 46,XX.ish del(22)(q13.31qter)(ARSA-,N85A-,SHANK3-)。3 岁时，她因暴发性肝衰竭需要紧急进行肝移植，可能是由病毒感染引发的超急性自身免疫性肝炎引起的。这是第二例报道的 22q13.3 缺失合并暴发性肝衰竭的患者。通过比较基因组杂交技术，我们在该患者中发现了一个 5.675Mb 的末端缺失（22q13.31 --> qter；包括约 55 个基因；从 NUP50 到 RABL2B），而在前一个患者中发现了一个 1.535Mb 的缺失（22q13.32 --> qter；包括约 39 个基因；从 BRD1 到 RABL2B）。PIM3 是这两个患者暴发性肝衰竭的一个候选主要基因；SHANK3/PROSAP2 也可能是另一个候选基因。我们建议在普莱汉姆-麦克德米德综合征患者的管理中进行肝功能检查和比较基因组杂交技术。该患者在肝移植后出现了发育追赶，这可能表明慢性肝脏疾病可能会导致其中一部分患者出现发育迟缓。
