CCBE1 mutations can cause a mild, atypical form of generalized lymphatic dysplasia but are not a common cause of non-immune hydrops fetalis

摘要

Generalized lymphatic dysplasia (GLD) results from an inherent developmental abnormality of the lymphatic system involving the viscera. The onset of failure of lymphatic drainage can be pre-or postnatal and can result in any combination of peripheral lymphoedema, pleural and pericar-dial effusions, ascites, chylous effusions and pulmonary or intestinal lymphangiectasia (1). GLD, in its more severe form, can present prenatally as hydrops fetalis (HF) (abnormal accumulation of fluid in two or more fetal compartments).Until recently, the only genes known to cause lymphatic disease were those implicated in disorders characterized by predominantly peripheral disease; FLT4 (VEGFR3) in Milroy disease and F0XC2 in lymphoedema distichiasis. In 2009, Connell et al. (2) described a pedigree in which a homozygous mutation in CCBE1 was identified as causing an autosomal recessively inherited GLD. In the family described, there were three affected siblings, all of whom presented in utero with HF. Two died and the third child had a phe-notype consistent with Hennekam syndrome, an autosomal recessive GLD disorder characterized by lymphoedema, lymphangiectasia, mental retardation and dysmorphic facies (3). Alders et al. (4) described homozygous and compound heterozy-gote CCBE1 mutations in 5/22 families with Hennekam syndrome.