We describe four unrelated children who were referred to two tertiary referral medical genetics units between 1991 and 2005 and who are affected with juvenile polyposis of infancy. We show that these children are heterozygous for a germline deletion encompassing two contiguous genes, PTEN and BMPR1A. We hypothesize that juvenile polyposis of infancy is caused by the deletion of these two genes and that the severity of the disease reflects cooperation between these two tumor-suppressor genes.

This 3-month study in 96 constipated children aged 6 months to 3 years confirms the long-term tolerance of PEG 4000 in pediatrics and indicates a PEG efficacy similar to or greater than that of lactulose.

Background-Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. Aims-To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. Patients-101 patients with coeliac disease and 130 healthy controls.Methods-Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. Results-The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p<0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p=0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p=0.002). These diVerences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/ DQB1*02 heterodimer. Conclusion-The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.

Background: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. Aim: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. Methods: A 24‐h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non‐responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response‐inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. Results: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration–time curve (P=0.003). The area under the plasma concentration–time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non‐responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. Conclusions: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg.

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Background-Thirty children operated on for Crohn's disease (CD) were reviewed (1975-1994). The aim of the study was to assess their postoperative outcome. Patients-19 boys and 11 girls, aged 15.3 (2) years (range 11.3-20) at surgery were studied. Results-Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned oV steroids, and 22 of 23 patients were weaned oV nutritional support; 17 patients without recurrrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years. Conclusion-Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children. (Gut 1998;43:634-638) Keywords: Crohn's disease; surgery; children Twenty years ago, 80% of patients with Crohn's disease (CD) underwent surgery within five years of onset, 1 but today the figure is under 50%.2 Surgery does not cure CD by resection of pathological segments, but transiently relieves the chronic abdominal illness. Postoperative endoscopic studies of adult CD have shown a high frequency of early recurrence (80% at one year 2 ). In contrast with the adult disease, old 3 4 and recent data 5-8 suggest that the prognosis for paediatric CD after surgery is fairly good, with prolonged remission and normal growth, particularly in cases of localised ileocaecal involvement. We report a retrospective study of 30 children operated on for CD, focusing on their postoperative outcome. Patients and methodsFrom 1975 to 1994, 119 children and adolescents were treated for CD in our department. Local surgery was performed for perianal disease in 29 cases (abscesses and fistula drainage, dilation of stenosis). Diagnostic laparotomies (n = 2) were excluded from the study as the diagnosis of CD was not known. So, 36 patients (30%) with CD underwent major surgery such as curative resection and/or strictureplasties in the Paediatric Surgery Department. The data for six of the patients were not available for analysis. The remaining 30 patients comprised 19 boys and 11 girls (sex ratio 1.7); the mean (SD) age at CD diagnosis was 12.2 (2) years (range 7.5-16.5) and the mean (SD) age at surgery was 15.3 (2) years (range 11.3-20). The mean number of flare ups before surgery was 2 (0.9) (range 0-4). The severity of CD before surgery was estimated by a paediatric CD activity index (>30 indicates severe disease). The sites of CD lesions were determined by radiology, upper gastrointestinal tr...

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