title: Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations.
abstract: The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as congenital lymphedema of the limbs and intestinal lymphangiectasia, accompanied by unusual facial morphology, variable intellectual disabilities and infrequently malformations. The syndrome is heterogeneous as mutations in the gene CCBE1 have been found responsible for the syndrome in only a subset of patients. We investigated whether it would be possible to predict the presence of a CCBE1 mutation based on phenotype by collecting clinical data of patients diagnosed with HS, with or without a CCBE1 mutation. We report here the results of 13 CCBE1 positive patients, 16 CCBE1 negative patients, who were clinically found to have classical HS, and 8 patients in whom the diagnosis was considered possible, but not certain, and in whom no CCBE1 mutation was identified. We found no statistically significant phenotypic differences between the 2 groups with the clinical HS phenotype, although the degree of lymphatic dysplasia tended to be more pronounced in the mutation positive group. We also screened 158 patients with less widespread and less pronounced forms of lymphatic dysplasia for CCBE1 mutations, and no mutation was detected in this group. Our results suggest that (1) CCBE1 mutations are present only in patients with a likely clinical diagnosis of HS, and not in patients with less marked forms of lymphatic dysplasia, and (2) that there are no major phenotypic differences between HS patients with or without CCBE1 mutations.
authors: Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: M
authors: M
authors: Alders
authors: A
authors: A
authors: Mendola
authors: L
authors: L
authors: Adès
authors: L
authors: L
authors: Al Gazali
authors: C
authors: C
authors: Bellini
authors: B
authors: B
authors: Dallapiccola
authors: P
authors: P
authors: Edery
authors: U
authors: U
authors: Frank
authors: F
authors: F
authors: Hornshuh
authors: S A
authors: SA
authors: Huisman
authors: S
authors: S
authors: Jagadeesh
authors: H
authors: H
authors: Kayserili
authors: W T
authors: WT
authors: Keng
authors: D
authors: D
authors: Lev
authors: C E
authors: CE
authors: Prada
authors: J R
authors: JR
authors: Sampson
authors: J
authors: J
authors: Schmidtke
authors: V
authors: V
authors: Shashi
authors: Y
authors: Y
authors: van Bever
authors: N
authors: N
authors: Van der Aa
authors: J M
authors: JM
authors: Verhagen
authors: J B
authors: JB
authors: Verheij
authors: M
authors: M
authors: Vikkula
authors: R C
authors: RC
authors: Hennekam
keywords: Autosomal recessive; CCBE1; Genotype-phenotype; Hennekam syndrome; Lymphangiectasia; Lymphatic dysplasia; Lymphedema
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