Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48912, USA.
Am J Perinatol. 2010 Feb;27(2):181-7. doi: 10.1055/s-0029-1234030. Epub 2009 Jul 30.
We report the clinical characteristics and the outcome of two cases of pontocerebellar hypoplasia (PCH) in one family. The objective of this report is to describe the mode of presentation, discuss the clinical course, and address the dilemma of prenatal diagnosis and the prospects for genetic diagnosis for PCH. The first case is a 4-year-old boy in whom the diagnosis was made in the neonatal period. Despite extensive prenatal follow-up during the mother's subsequent pregnancy, prenatal diagnosis could not be made and a second affected child was born. Both siblings have severe developmental delay. The cases raise an important ethical dilemma about the most appropriate intervention if the mother of a child affected with PCH becomes pregnant. PCH is considered to have an autosomal-recessive mode of inheritance and a recurrence risk of 25% in each pregnancy. Until recently when genetic mutations in PCH types 2, 4, and 6 began to be identified, the lack of well-recognized genetic testing precluded experts from making clear recommendations. The best advice to these parents was difficult or elusive. With two children currently affected, should the parents terminate or continue with the latest pregnancy? Extensive monitoring with serial prenatal ultrasound failed in the previous pregnancy and resulted in the birth of the second affected child. It is evident that serial ultrasound scan may not be helpful in making the diagnosis prenatally. Therefore, other diagnostic modalities such as magnetic resonance imaging may be necessary and should be considered. With the identification of genetic basis or mutations in PCH types 2, 4, and 6 and possible development of commercial genetic testing for these types of PCH, reproductive decision or genetic testing during pregnancy should be recommended to affected families to enable informed choices.
我们报告了一个家庭中两例桥脑小脑发育不全症（PCH）的临床特征和结局。本报告的目的是描述其发病形式，讨论临床病程，并解决 PCH 的产前诊断和遗传诊断的难题。第一例为 4 岁男孩，在新生儿期作出诊断。尽管在其母亲随后妊娠期间进行了广泛的产前随访，但仍未能作出产前诊断，第二个受累儿出生。两例同胞均有严重的发育迟缓。如果 PCH 患儿的母亲再次妊娠，就会出现一个重要的伦理难题，即如何选择最合适的干预措施。PCH 被认为是常染色体隐性遗传，每次妊娠的复发风险为 25%。直到最近，当 PCH 类型 2、4 和 6 的基因突变开始被识别出来，缺乏公认的基因检测使得专家无法提出明确的建议。给这些父母的最佳建议是困难或难以捉摸的。目前已有两个孩子受累，父母应该终止还是继续最新的妊娠？在前一次妊娠中，连续的产前超声监测失败，导致第二个受累儿的出生。显然，连续的超声扫描可能无助于产前诊断。因此，可能需要考虑其他诊断方式，如磁共振成像。随着 PCH 类型 2、4 和 6 的遗传基础或突变的确定，以及这些类型 PCH 的商业基因检测可能的发展，应该向受累家庭推荐生殖决策或妊娠期间的基因检测，以使其能够做出知情选择。
