Abstract
BACKGROUND: Mutations in CCBE1 have been found to be responsible for a subset of families with autosomal recessive Hennekam syndrome. Hennekam syndrome is defined as the combination of generalized lymphatic dysplasia (ie. lymphedema and lymphangiectasia), variable intellectual disability and characteristic dysmorphic features. The patient we describe here has a lymphatic dysplasia without intellectual disability or dysmorphism caused by mutation in CCBE1, highlighting the phenotypic variability that can be seen with abnormalities in this gene. CASE PRESENTATION: Our patient is a 5 week old child of Pakistani descent who presented to our center with generalized edema, ascites, and hypoalbuminemia. She was diagnosed with a protein losing enteropathy secondary to segmental primary intestinal lymphangiectasia. As the generalized edema resolved, it became clear that she had mild persistent lymphedema in her hands and feet. No other abnormalities were noted on examination and development was unremarkable at 27 months of age. Given the suspected genetic etiology and the consanguinity in the family, we used a combination of SNP genotyping and exome sequencing to identify the underlying cause of her disease. We identified several large stretches of homozygosity in the patient that allowed us to sort the variants found in the patient's exome to identify p.C98W in CCBE1 as the likely pathogenic variant. CONCLUSIONS: CCBE1 mutation analysis should be considered in all patients with unexplained lymphatic dysplasia even without the other features of classic Hennekam syndrome.