Background: Cornelia de Lange syndrome (CdLS) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth problems and development delay. The high clinical and genetic variability the existence of a CdLS Spectrum has been recently suggested 1.
Up to 80% of CdLS patients are assumed to have symptoms of gastroesophageal reflux disease (GERD) which may become apparent in a highly variable manner 2 3. The aim of this study is to retrospectively describe a set of 23 CdLS patients who underwent Nissen Fundoplication (NF) for GERD, correlating with clinical and genetic features. Few data are present in Literature 4. Moreover in this study we would like to find possible predictive factors for surgical treatment for GERD.
Methods
Data were collected retrospectively in all CdLS patients undergoing NF for GERD.
Results
Mean age of patients was 9.5 years; mean age of surgical treatment was 4 years. There were 13 females and 10 males. 21/23 (91.3%) of our patients had a molecular characterization, while 2/23 (8.6 %) had a clinical diagnosis according the new criteria1. In patients with a known molecular defect, 21/21 (100%) showed an NIPBL gene mutation, truncating in 12/21 (52.2%).
Patients presented predominantly underweight with a BMI less than 10th centile in 14/23 (60.9%). Regarding intellectual disability 5, most patients have a severe-profound intellectual disability (13/23, 56.5%), while 7/23 (30.4%) were moderate and only 3 patients had a borderline mild development (13%). Upper limb malformations were evident in 10/23 (44%).
21/23 (91%) patients that underwent NF had previously performed an extended ineffective drug treatment with protein pump inhibitors (PPI). The great majority of our patients presented with atypical behavioural symptoms not controlled by medical therapy.
Endoscopy revealed pathological findings in 14 cases (9 esophagitis, 4 hiatal hernia, 1 Barrett’s esophagus). Most of the patients (18/23; 78%) underwent isolated intervention of NF. In 2 patients it was performed during surgical correction of diaphragmatic hernia and in 3 patients there was direct NF in conjunction with placement of gastrostomy tube.
For 21/23 (91.5%) patients, clinical follow-up showed good results while in 2/23 (8.5%) a second surgical intervention was necessary. The major medical complication after NF was dumping syndrome observed in 4/23 patients (17%); this situation resolved within 1 year.
Discussion
We have described our set of patients undergoing NF. We highlight that all tested patients have an NIPBL mutation, frequently associated with a more severe clinical phenotype. Accordingly, most of our patients presented with severe-profound Intellectual Disability and a poor weight gain. Clinical GERD symptoms are often irritability, hyperactivity and behavioral changes with self-harm. Endoscopic findings in patients who underwent NF included esophagitis, PPI not responsive in most patients.
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- ^ Cereda, A. et al. A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 172, 179–189 (2016).